Articles https://www.longecity.org/forum/page/index2.html Mon, 23 Sep 2019 09:50:53 +0000 86400 Manage articles SelfTesting Programme https://www.longecity.org/forum/page/index2.html/_/feature/assays "Biomarkers of Aging Self Experimentation (BASE)"

This is our current flagship programme in this field. BASE’s goal is to better comprehend aging interventions over time and present this data in a useful way.
We are inviting participants to contribute age biomarker data alongside information about their lifestyle and nutrition.
To participate, anyone may complete the BASE Questionnaire anonymously. Qualifying participants may claim a partial reimbursement. 
Results will be shared internally among participants, with a view towards generating an open source database.
The initiative is at an early stage - parameters are likely to change and we are very open to feedback.
⇒ https://www.longecity.org/base/


"Aging Biomarkers"

We all know that biologically and medically, people age at different rates. Understanding why could be a key part in retarding or reversing aging. However, measuring biological age is far more complicated than counting chronological age. In recent years various new methods have been proposed. 
In 2018 LongeCity started a programme supporting our Members in gaining experience with these tests by granting a subsidy for procuring these tests from selected service providers on the condition that the Members self-report the results and their experiences ⇒ on our internal forum. (link) 
We remain very interested in evaluating new biomarkers of aging. We will follow the results of this initiative and support others like the ⇒ AGEMETER tool.    


"N=1 Experiments" 

Since our founding, this site has attracted individuals who are impatient for the state of medical consensus to advance and are experimenting with supplements, techniques and experimental compounds. This has many pitfalls: first and foremost the risk to the individual, the flavour of chasing ‘magic’ that has always tainted the life-extension field, along with the dreadful folly of ‘testimonials’; the risk of generating the flawed impression that taking life extending supplements must somehow be ‘felt’ quickly; a turning away from the principles of scientific equipoise and the hard truths of evidence-based medicine.
Nonetheless this self-experimentation goes on and has some aspects that are worth celebrating: the intensive and personalised engagement with scientific evidence; the assumption of individual responsibility for health and wellbeing; the ongoing adventure of discovery that would not be possible without plenty of risk-takers. To be clear: Faced with these perspectives, LongeCity as an organisiation maintains absolute neutrality. We do not in any way encourage or promote self-experimentation, nor do we condemn and suppress evidence of it. We do however, wish that some ‘self experiments’ were more responsibly planned, conducted, and reported with a view towards generating the most reliable dataset possible. We have therefore set aside some potential funding to complement those experiments that have the potential to yield insights that could be of generalisable interest to the LongeCity community. 

Generally, the scheme works as follows: 
- An individual (the Subject) develops a supplement or other regimen based on an informed review of the literature, community advice and the available sources. 
- The Subject develops a testing plan that assesses meaningful metabolic parameters at meaningful intervals. 
- The Subject commences the regimen. The Subject pays for all supplies and the baseline test which must be published on LongeCity in annonymised form. 
- LongeCity can be approached to pay for a subsequent test. This does not entail an endorsement of the experiment but simply a desire to further asses some of the safety and efficacy parameters in question.
If you want to participate in this initiative, please ⇒ contact us.

]]> Wed, 07 Aug 2019 17:23:00 +0000 bd686fd640be98efaae0091fa301e613 Pioneers: Marquis de Condorcet (1743-1794) https://www.longecity.org/forum/page/index2.html/_/feature/condorcet The 18th-century Age of Enlightenment brought forth a paradigm shift in perceptions of the human condition and potential. The thinkers of the Enlightenment systematically articulated the case for rationality, science, and technology dramatically improving human well-being and overcoming what were previously considered to be immutable limitations. Those of us today who support the pursuit of indefinite life extension, rejuvenation biotechnology, and emerging research and its applications in a wide array of transformative fields are essentially continuing the project that the Enlightenment philosophers began. Although they had a much more rudimentary toolkit at their disposal, the most visionary minds among them were remarkably able to anticipate many aspects of our contemporary world and even to see beyond it. 
One such individual was Marie-Jean-Antoine-Nicolas de Caritat, Marquis de Condorcet (1743-1794), among the most talented polymaths, philosophers, economists, political scientists, mathematicians, administrators, and authors of the 19th century – a man who unfortunately lived far ahead of his time and whose life was claimed by the tumult of the French Revolution in 1794. Condorcet died in prison under mysterious circumstances, after running afoul of the murderous Jacobin faction that seized power in 1793-1794 and perpetrated a Reign of Terror that subverted the ideals of the Enlightenment. Shortly beforehand Condorcet completed a work that set forth the blueprint for human progress to come – the Esquisse d'un tableau historique des progrès de l'esprit humain (Outlines of a historical view of the progress of the human mind), published posthumously in 1795. At the end of this work, Condorcet briefly but insightfully articulated much of the terminology and conceptual framework that characterize many thoughts in the life-extension movement today. 

Condorcet divides human history into ten epochs, the first nine of which bring the human species to the era of the French Revolution; the tenth epoch is Condorcet’s vision for humankind’s future. Much of what Condorcet articulated has already come to pass – including dramatic improvements in agricultural and industrial processes, broadening of education, major progress toward gender equality, and decreases in the average number of children per family as economic development, education, and living standards have improved. Condorcet even posited an early version of what is today known as the “law of accelerating returns” (a phrase popularized in our era by Ray Kurzweil):

" All the causes which contribute to the improvement of the human species, all the means we have enumerated that insure its progress, must, from their very nature; exercise an influence always active, and acquire an extent for ever increasing. The proofs of this have been exhibited, and from their development in the work itself they will derive additional force: accordingly we may already conclude, that the perfectibility of man is indefinite. (Condorcet 289-290) "

Regarding improvements in longevity, our era already features some of the developments that Condorcet anticipated. In Condorcet’s time, most people still did not die of biological “old age”; average life expectancy in France remained below age 30 for much of the 18th century (ref), and rich and poor alike often fell victim to infectious diseases, warfare, political turmoil, and poor lifestyle habits before reaching any advanced age – and high rates of reproduction accompanied (and were in part motivated by) devastatingly high rates of infant mortality. For Condorcet, bringing average life expectancies into the late seventies and early eighties, as is the case for virtually all “developed” countries today, would have constituted astonishing progress. Condorcet focused first on the major proximate causes of mortality in his time – malnutrition, lack of sanitation, poor living conditions, unhealthy work environments, and life-shortening vices – including lack of physical exercise and the indolence that he associated with the luxury of the aristocracy. Regarding the overcoming of these perils, Condorcet observed: 

" This law [of the perfectibility of organic life] extends itself to the human race; and it cannot be doubted that the progress of the sanative art, that the use of more wholesome food and more comfortable habitations, that a mode of life which shall develop the physical powers by exercise, without at the same time impairing them by excess; in fine, that the destruction of the two most active causes of deterioration, penury and wretchedness on the one hand, and enormous wealth on the other, must necessarily tend to prolong the common duration of man’s existence, and secure him a more constant health and a more robust constitution. (Condorcet 290) "

The methods of human rationality, as directly accessible to the mind and capable of being implemented through societal reforms, could achieve the kinds of lifestyle-related improvements Condorcet described. But he ventured further to address the even more significant potential lifespan extension that medical progress could unlock: 

" It is manifest that the improvement of the practice of medicine, become more efficacious in consequence of the progress of reason and the social order, must in the end put a period to transmissible or contagious disorders, as well to those general maladies resulting from climate, aliments, and the nature of certain occupations. Nor would it be difficult to prove that this hope might be extended to almost every other malady, of which it is probable we shall hereafter discover the most remote causes. (Condorcet 290-291) "

Condorcet’s prognostications directly address the question of what will remain once the most proximate 18th century causes of death and disease (infections, poor climate, bad working conditions) are greatly diminished. In our time, this has essentially happened, and heart disease, cancer, and degenerative illnesses of the brain have become the most common killers (and even the rates of death from some of these ailments are in decline). Condorcet’s contemporaries did not understand the causes of these then-rarer ailments (since most did not live long enough to get them), but we now know them all to be consequences of the degenerative processes of biological aging at the cellular and molecular levels. Condorcet recognized that the mindsets and methods of Enlightenment rationality could be applied to identify and defeat these maladies as well – and the outcome would be indefinite longevity:

" Would it even be absurd to suppose this quality of melioration in the human species as susceptible of an indefinite advancement; to suppose that a period must one day arrive when death will be nothing more than the effect either of extraordinary accidents, or of the slow and gradual decay of the vital powers; and that the duration of the middle space, of the interval between the birth of man and this decay, will itself have no assignable limit? Certainly man will not become immortal; but may not the distance between the moment in which he draws his first breath, and the common term when, in the course of nature, without malady or accident, he finds it impossible any longer to exist, be necessarily protracted? As we are now speaking of a progress that is capable of being represented with precision, by numerical quantities or by lines, we shall embrace the opportunity of explaining the two meanings that may be affixed to the word indefinite. (Condorcet 291) "

The distinction between “indefinite life extension” as the prolongation of lifespans without a fixed upper bound and “immortality” in the sense of indestructability or invulnerability is important for advocates of longevity today and have been repeatedly articulated to persuade the general public to recognize that the life-extension project is the logical continuation of the improvements in medicine, lifestyle, and environment which have already brought about major lifespan increases during the past two centuries. Condorcet was the first to articulate that distinction; when we speak of indefinite life extension, we are indeed building upon Condorcet’s vision and carrying it forward using the next generation of medical technologies. 

Condorcet did not definitively posit whether or not there is some remoter upper bound to possible lifespans, but he did explore both possibilities: 

" In reality, this middle term of life, which in proportion as men advance upon the ocean of futurity, we have supposed incessantly to increase, may receive additions either in conformity to a law by which, though approaching continually an illimitable extent, it could never possibly arrive at it; or a law by which, in the immensity of ages, it may acquire a greater extent than any determinate quantity whatever that may be assigned as its limit. In the latter case, this duration of life is indefinite in the strictest sense of the word, since there exist no bounds on this side of which it must necessarily stop. And in the former, it is equally indefinite to us; if we cannot fix the term, it may for ever approach, but can never surpass; particularly if, knowing only that it can never stop, we are ignorant in which of the two senses the term indefinite is applicable to it: and this is precisely the state of the knowledge we have as yet acquired relative to the perfectibility of the species. (Condorcet 291-292) "

Whatever other limits, if any, humans might come to face if they live centuries or longer, Condorcet convincingly demonstrates that we will never be certain that such limits have been reached – so the possibility of indefinite longevity and the striving toward it are always the appropriate working hypothesis and practical approach. Condorcet’s empirical prediction, which has held true thus far (with temporary aberrations in times of major warfare or societal turmoil), is that mean life expectancy will continue to increase without end:

" we are bound to believe that the mean duration of human life will for ever increase, unless its increase be prevented by the physical revolutions of the system; but we cannot tell what is the bound which the duration of human life can never exceed; we cannot even tell, whether there be any circumstance in the laws of nature which has determined and laid down its limit” (Condorcet 292).  "

It is fitting for Condorcet to conclude his treatise – the last work of his life – by pointing to a gloriously open-ended future, where the same miseries and oppressions that shortened his own life need not befall future generations. A great mind born too soon, Condorcet could not prevent his own death but could bestow a vision for us to implement:

" This sentiment is the asylum into which he retires, and to which the memory of his persecutors cannot follow him: he unites himself in imagination with man restored to his rights, delivered from oppression, and proceeding with rapid strides in the path of happiness; he forgets his own misfortunes while his thoughts are thus employed; he lives no longer to adversity, calumny and malice, but becomes the associate of these wiser and more fortunate beings whose enviable condition he so earnestly contributed to produce. (Condorcet 294) "

Many in life extension may feel called by this heroically ambitious, boldly optimistic project for the transformation of humankind – whose epitome and, indeed, the central aim, is the extension and expansion of lifespans without bounds.

]]> Wed, 26 Dec 2018 12:47:47 +0000 58a2fc6ed39fd083f55d4182bf88826d Aging Biomarker Testing Support Programme https://www.longecity.org/forum/page/index2.html/_/feature/biomarkers Background

LongeCity.org has long been a hotbed of information exchange and discussion about various methods of slowing or reversing the process of aging. An incredible number of supplements have been tried, exercise routines employed, and eating patterns explored.
Is it any of it working? Have LongeCity members succeeded in slowing aging and remaining healthier than their contemporaries?
Precious few people maintain a regular schedule of objective testing for health and aging biomarkers. Even fewer make those results public. LongeCity aims to change this state of affairs. 
In order to foster a ‘citizen scientist’ culture of objective self-monitoring and knowledge sharing LongeCity is supporting all Immortality Institute Members in procuring tests for next-generation biological age markers.


Which tests are supported?

Generally, tests that rely on epigenetic aging markers to give a ‘biological age’ profile and are easily obtainable through reputable third-party testingproviders.

    Currently the following commercially available tests are supported:
     • Epimorphy (https://www.mydnage.com/)
     • Osiris Green (https://www.osirisgreen.com/)
     • TeloYears (https://www.teloyears.com/)

While these tests fit the above description, they are quite different in what they measure. Make sure you use the resources on longecity and elsewhere to make an informed decision which test to choose. Further reading.
Currently our subsidy programme combined with a provider discount means that one of these tests is available to Immortality Institute Members for free or at a substantial discount.
Members can suggest other tests to be included in the list. Contact us with suggestions and references.


Steps for Participants

STEP 1. You need to be a Member of the Immortality Institute. (If you are not yet a member - it may well be worth joining since the discount for the test more than covers your membership donation.)

STEP 2. Register your interest here. (Do not just go and order your test! Wait until you get the ‘all clear’and discount code from the Membership Secretary via forum PM.)

STEP 3. Order the test from the provider using the discount code provided. (Please note that this will involve paying the provider upfront and making sure that you collect your biological samples as instructed and mail them back to the provider) 

STEP 4. Post your results here. The minimum information required is your real (calendar) age and your biological age as determined by the test. However, we’d really like you to share as much information as you think may be pertinent regarding lifestyle, diet, supplementation etc. that might shine a light on your results for further analysis. You don’t have to disclose your name and address).

STEP 5. LongeCity will reimburse you the costs of the test up to a maximum of $150 via paypal to your registered email address.



Note The support programme is a voluntary community effort. Particants in the programme do so at their own risk and responsibility. Any arrangements with third party testing services are private contracts between the service providerand the individual participants. LongeCity makes no guarantees regarding thequality, safety and reliability and utility of any third party tests. Financial support is provided at LongeCity's sole discretion, is not guaranteed and subject to available funds.


]]> Fri, 18 May 2018 20:57:57 +0000 0aa1883c6411f7873cb83dacb17b0afc <![CDATA[Aging Theories: is an 'aging program' a...]]> https://www.longecity.org/forum/page/index2.html/_/articles/agingtheories2018a The big and continuing mystery about aging has been as described by Vit Zemanek in his recent Longecity article [1]
“When Darwin’s theory of evolution by natural selection was established, biologists were puzzled by the existence of senescence and aging among all organisms. 
Why did the evolutionary pressure not produce immortal species?”

A further question might be: why does aging ‘look’ so much like other evolved traits? Why is it that aging (and internally determined lifespan) varies between individual members of a species and varies to a much greater extent between different species?
Unfortunately Zemanek’s account ends prior to the development of modern programmed aging theories, which are emerging as a major force in developing anti-aging medicine. 
Programmed aging theories contend that organisms have developed biological mechanisms (“programs”) that purposely limit individual lifespans in order to obtain an evolutionary benefit for a population of individuals that possess the program. Organisms -including humans- possess what amounts to a biological ‘suicide mechanism’. The drastic increase with age seen in highly age-related diseases and conditions is the result of this ‘aging program’. 

Some theorists have supported the idea that a trait (like programmed aging) can evolve to benefit a population even at the expense of individual members [6]. “Benefit” in this case means increasing the probability that the population will expand, escape extinction, and produce descendant species. 
But does the evolution process operate to benefit a population, or individual members of a population? Many proponents of non-programmed theories such as Tom Kirkwood, (author of the disposable soma theory [4]), dismissed programmed aging theories and other theories based on population benefit because of the conflict with Darwin’s evolutionary mechanics. Some analyses in the 1960’s [10] were also cited as definitively defeating population benefit concepts such as group selection (first proposed in 1962), kin selection, and small-group selection. August Weismann originally considered programmed aging in 1882 [5] but eventually changed his position. A series of aging theories are based on population-oriented evolutionary mechanics concepts originated by Peter Medawar in 1952 [2]. He proposed that the lifespan needed by an organism is highly dependent on species and population-specific circumstances such as age at reproductive maturity and extent of predation. Other authors of the early population benefit theories (e.g. [11) were mainly trying to explain other observed discrepancies with Darwinian mechanics such as animal altruism and were therefore relatively unconcerned with theoretical gerontology. 
However today there are multiple aging theories based on population benefit [6,7,8,9]). Some [6] specifically propose solutions for the evolutionary mechanics issues based on modern genetics discoveries that support population benefit and thereby programmed aging.
One can compare published efforts (e.g. [12] and [13]) to contradict the new programmed theories as well as counter arguments (e.g. [15,16,17,18]). Note that many modern non-programmed aging theories also require population-oriented modifications to Darwin’s mechanics. 

Empirical observations that may favour programmed theories include:
• Explicit suicide mechanisms have been found in some organisms such as octopus [21] and roundworm [22]. 
• Human genetic diseases Hutchinson-Guilford progeria and Werner’s syndrome simultaneously accelerate many or most symptoms of aging including age-related diseases [23] suggesting a defect in a common mechanism that controls the diverse symptoms. 
• Genetic engineering has produced roundworms that live 10 times as long as wild worms [24] suggesting existence of a program. 
• Some species (e.g. Pacific rockfish) have been identified that apparently do not age [25]. This is a problem for non-programmed aging theories that have difficulties explaining why an apparently internally immortal species would exist. Programmed theories suggest these species could be the result of a fault (e.g. mutation) that disabled their program and therefore increased the probability that the population would become extinct [19].

Why is this theoretical question of such crucial relevance? 
The programmed vs. non-programmed issue is critically important to medical efforts toward dealing with aging and age-related diseases precisely because of the “unifying factor” question. 
As described by antagonistic pleiotropy theory author George Williams in 1957 [3], nonprogrammed theories strongly suggest that there is no treatable common cause of the many different age-related diseases and conditions and thus no unifying factor. Western medicine is largely based on the idea that each individual age-related disease or condition has different causes that need different treatments. Non-programmed theories strongly support this view. Programmed theories strongly suggest that there are common factors (elements of the program mechanism) behind the different age-related diseases and conditions. 
I argue that the emergence of modern programmed aging theories provides a sound theoretical basis for new approaches in developing medical treatments for highly age-related diseases and conditions as well as a basis for the idea that human lifespan can be generally increased.



References:

1 Zemanek V. Aging theories: Is there a unifying factor in aging? Longecity 
2 Medawar, P.B, An Unsolved Problem of Biology., 1952. H.K. Lewis & Co., London. 
3 Williams, G Pleiotropy, natural selection and the evolution of senescence,. 1957. Evolution 11, 398-411 
4 Kirkwood T.B.L. & F.R.S. Holliday, The evolution of ageing and longevity, 1979. Proceedings of the Royal Society of London B 205: 531-546 
5 Weismann A. Uber die Dauer des Lebens. 1882 Fischer, Jena 
6 Goldsmith T. (2017) Evolvability, Population Benefit, and the Evolution of Programmed Aging in Mammals. Biochemistry (Moscow), 2017,Vol. 82, No. 12, pp. 14231429 DOI:10.1134/S0006297917120021 
7 Skulachev V. Aging is a Specific Biological Function Rather than the Result of a Disorder in Complex Living Systems: Biochemical Evidence in Support of Weismann's Hypothesis. Biochemistry (Mosc). 1997 Nov;62(11):1191-5. PMID: 9467841 
8 Libertini G (1988) An adaptive theory of increasing mortality with increasing chronological age in populations in the wild. J. Theor. Biol. 132. 145-162. 
9 Mittledorf J. Chaotic Population Dynamics and the Evolution of Ageing. Evolutionary Ecology Research 2006, 8: 561-574 
10 Williams G. Adaptation and Natural Selection: A Critique of Some Current Evolutionary Thought, Princeton UP. ISBN 0-691-02357-3 1966 
11 Wynne-Edwards V. Animal Dispersion in Relation to Social Behaviour, Edinburgh: Oliver & Boyd, 1962 
12 Kowald A, Kirkwood T. Can aging be programmed? A critical literature review Aging Cell 2016 doi: 10.1111/acel.12510 
13 Kirkwood T, Melov S. On the programmed/non-programmed nature of ageing within the life history. Curr Biol. 2011 Sep 27;21(18):R701-7. doi: 10.1016/j.cub.2011.07.020 
--
15 Goldsmith T. On the programmed/ non-programmed aging controversy Biochemistry (Moscow) 2012 Vol 77 Nr 7 729-7322012 doi: 10.1134/S00629791207005X PMID: 22817536 
16 Goldsmith T Aging is programmed! (A response to Kowald-Kirkwood “Can aging be programmed? A critical literature review”) DOI: 10.13140/RG.2.2.36205.38883 
17 Skulachev V. Aging as a particular case of phenoptosis, the programmed death of an organism (a response to Kirkwood and Melov "On the programmed/non-programmed nature of ageing within the life history"). Aging (Albany NY). 2011 Nov;3(11):1120-3 
18 Goldsmith T. Arguments against non-programmed aging theories Biochemistry (Moscow) Phenoptosis 78:9 971-978 2013 
19 Goldsmith T. The Evolution of Aging – 3 rd ed. 2014 Azinet Press Annapolis ISBN 9780978870959 
--
21 Wodinsky J. 1977. Hormonal inhibition of feeding and death in octopus: control by optic 
gland secretion. Science, 198: 948–951. 
22 Apfeld J, Kenyon C. Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 1999. 
23 Gray, Md; Shen, Jc; Kamath-Loeb, As; Blank, A; Sopher, Bl; Martin, Gm; Oshima, J; Loeb, La (Sep 1997). The Werner syndrome protein is a DNA helicase. Nature genetics 17 (1): 100–3. 
doi:10.1038/ng0997-100. PMID 9288107 
24 Kenyon, C. Regulation of Life-Span by Germ-Line Stem Cells in Caenorhabditis elegans, , Science (Vol. 295, 18 January 2002) 
25 Bennett, J.T. et al. Confirmation on longevity in Sebastes diploproa (Pisces: Scorpaenidae) from 210Pb/226Ra measurements in otoliths. 1982. Maritime Biology. 71, 209-215.

further material at http://aging-theories.org

]]> Wed, 18 Apr 2018 18:00:26 +0000 cfecdb276f634854f3ef915e2e980c31 Antioxidants- relevant for life extension? https://www.longecity.org/forum/page/index2.html/_/articles/antioxidants2018c
Harman published his free radical theory of aging in 1956 and in the following decades it slowly became probably the most popular explanation of the mechanism of aging (Ashok & Ali, 1999). Because the theory claims that reactive oxygen species damage macromolecules (more details in my previous article “Aging theories: Is there a unifying factor in aging?”), the effects of substances known as nutritional antioxidants have received a lot of attention. The underlying theory that has been long accepted says that antioxidants may  improve health (and eventually prolong lifespan) by lowering the level of oxidative stress present in the organism because they eliminate free radicals, usually by 'donating' a free electron.   
However, there is a controversy about validity of this theory because some researchers reached the opposite conclusion. They view reactive oxygen species as signal molecules important for mitochondrial processes and cellular communication (Hamanaka & Chandel, 2010; Ristow & Schmeisser, 2011). It becomes clear that reactive oxygen species are not necessarily always harmful  (Brigelius-Flohé, 2009). A research of EGCG from green tea suggested antioxidants may be potent agents causing reductive damage (Lu, Ou, & Lu, 2013). It was observed that antioxidant consumption may neutralize any positive outcomes of exercising (Ristow et al., 2009). According to the meta-analysis of available clinical data about vitamin supplementation, the consumption of beta-carotene, vitamin A, or vitamin E has been associated with higher all-cause mortality (Bjelakovic, Nikolova, Gluud, Simonetti, & Gluud, 2012). One Danish research group found association between supplemented folic acid and increased all-cause mortality (Roswall et al., 2012). On the other hand, other researchers did not identify any effects on mortality (Henríquez-Sánchez et al., 2015) or even found the inverse association (Zhao et al., 2016; Bastide et al., 2017). It is possible that some unknown factors are in play which lead to controversy and confusion caused by so many different results.

The most well-known antioxidant is probably L-ascorbic acid, so-called vitamin C. Human body is unable to synthesize it and its absence or deficiency in diet causes fatal disease known as scurvy. However, the level of vitamin C in blood plasma is strictly regulated by organism, therefore high oral doses of L-ascorbic acid in any form do not elevate its plasma levels accordingly (Padayatty et al., 2004). There has been a lot of research done about potential effects on aging-related diseases, but the currently available evidence does not support any benefits (“Vitamin C Fact Sheet for Health Professionals,” 2016). Although, according to some researchers, there is a potential to use L-ascorbic acid intravenously in cancer treatment (Padayatty, Riordan, Hewitt, Katz, Hoffer, & Levine, 2006).

Another antioxidant which received a lot of attention is alpha-tocopherol, the only form of vitamin E with high enough biological activity to meet human requirements. Recommended daily intake is less precisely determined, compared to vitamin C. No beneficial effects were confirmed in studies with high number of participants (“Vitamin E Fact Sheet for Health Professionals,” 2016), some researchers even proposed possible harmful effects, such as increased general mortality in supplemented groups (Bjelakovic, Nikolova, Gluud, Simonetti, & Gluud, 2007).

Carotenoids also display antioxidant properties, the most popular of them is beta-carotene, sometimes called provitamin A (“Vitamin A Fact Sheet for Health Professionals,” 2016). Unfortunately, no benefits have received sufficient support by multiple studies. And it has been suggested that beta-carotene was found to increase the risk of lung cancer and cardiovascular diseases (The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, 1994; Goodman et al., 2004). Another molecule from this group is lycopene, results of studies are mixed but the data from The Health Professionals Follow-up Study indicate a reduced risk of prostate cancer (Giovannucci, Liu, Platz, Stampfer, & Willett, 2007). Lutein seems to decline age-related macular degeneration (Richer et al., 2004). Astaxanthin is the strongest carotenoid antioxidant (Ursoniu, Sahebkar, Serban, & Banach, 2015) and researchers claim it has beneficial effects on humans (Cohaire, Garem, Mahmoud, Eertmans, & Schoonjans, 2005) but no large study was yet concluded.

Plant polyphenols (and their most numerous subgroup flavonoids) are abundant in nature as well as in our diet, and are generally nontoxic (Yao et al., 2004; Manach, Scalbert, Morand, Remesy, & Jimenez, 2004). In spite of these facts, they received scientific attention only for a short period of time, compared to aforementioned antioxidants. It is worth to note that recent research shows their potential benefits go often well beyond antioxidant mechanism (Scalbert, Johnson, & Saltmarsh, 2005; Kim, Quon, & Kim, 2014; Srivastava & Mishra, 2015).

The grape derived flavonoid polyphenolic substance resveratrol became widely known in anti-aging circles but shows very little bioavailability in vivo (Goldberg, Yan, & Soleas, 2003) and no lifespan extension in mammals has been conclusively shown.

Good, popular and easy-to-access source of catechins and other flavonoids is tea. According to many studies, its chemical composition provides antioxidant, anticancer, neuroprotective, cardioprotective and other beneficial health effects (Fujiki et al., 1999; Rietveld & Wiseman, 2003; Caruana & Vassallo, 2015). EGCG, or epigallocatechin-3-gallate, is a major tea polyphenol (Nagle, Ferreira, & Zhou, 2006; Singh, Shankar, & Srivastava, 2011). Interestingly, bioavailability of tea polyphenols does not change with the addition of milk (Kyle, Morrice, McNeill, & Duthie, 2007).

Curcumin, the main physiologically active polyphenol of turmeric, shows antioxidant and anti-inflammatory properties in humans (Ursoniu, Sahebkar, Serban, & Banach, 2015) and exhibits high level of safety and tolerability (Gupta, Patchva, & Aggarwal, 2013). Although, its bioavailability is very poor if taken alone, but drastically increases by about 2000% if consumed with an addition of piperine (Shoba et al., 1998). Other promising techniques of enhanced drug delivery are also being investigated (Prasad, Tyagi, & Aggarwal, 2014).

The most important antioxidant for humans is probably endogenous glutathione which is abundantly present in our cells. It scavenges free radicals very efficiently, directly regulates immune functions and levels of oxidative stress (Wu, Fang, Yang, Lupton, & Turner, 2004; Pizzorno, 2014). Furthermore, recent research conducted on humans showed that daily glutathione consumption can significantly increase its body stores (Richie et al., 2014). N-acetylcysteine supplementation boosts glutathione biosynthesis (Pendyala & Creaven, 1995).

Alpha lipoic acid (and its reduced form, dihydrolipoic acid), another interesting endogenous antioxidant, is crucial for mitochondrial functions (Palaniappan & Dai, 2007). It is also a chelator substance as it has the ability to eliminate metal ions but do not cause metal depletion in organism. Alpha lipoic acid is able to reduce the oxidized forms of vitamin C and E (Gomes & Negrato, 2014). Orally supplemented lipoic acid accumulates in tissues and evidence suggests its antioxidant properties are indirect but still beneficial (Shat, Moreau, Smith, Smith, & Hagen, 2009).

Coenzyme Q10 plays a key role in mitochondrial and other metabolic processes. It displays antioxidant properties and can be supplemented orally (Littarru & Tiano, 2007). Aging related Q10 deficiency has been linked to cardiovascular diseases (Singh, Devaraj, & Jialal, 2007). Research showed that sufficient intake can prevent or treat these issues (Kumar, Kaur, Devi, & Mohan, 2009; Mortensen et al., 2014) but another review study calls for trials with better design (Flowers, Hartley, Todkill, Stranges, & Rees, 2013).

Melatonin also participates in the protection from oxidative damage by stimulation of glutathione production (Fusco, Colloca, Lo Monaco, & Cesari, 2007). Particularly high concentrations were found in cell nucleus and mitochondria (Aydogan, Yerer, & Goktas, 2006). Melatonin is well-known as a sleep hormone and in darkness is naturally produced by brain (Peuhkuri, Sihvola, & Korpela, 2012).

Typical age-related diseases are cardiovascular, cancer, type 2 diabetes, Alzheimer’s disease (Everitt et al., 2006). Interestingly, they cause about 90 percent of deaths annually in industrialized countries (de Grey, 2007). Therefore, if antioxidants were effective in reducing these health problems, we could claim they are relevant for life extension, even if they are not relevant for the extension of maximal lifespan. However, whether or not this is the case remains controversial, especially in the case of certain vitamins (as described above). One speculation would be that the contradicting results might be explained by the non-homogeneous of vitamins among the population (Semba, 2012). Antioxidants in the diet seem to be a necessity but the benefits of dietary supplement consumption remain questionable. Some supplements contain unnecessarily high doses which do not offer any benefits but may even lead to adverse effects. On the other hand, the health impact of some polyphenolic antioxidants seems to go well beyond their basic antioxidant mechanism (Scalbert, Johnson, & Saltmarsh, 2005). 


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View attachment: LCantiox.png

---- LongeCity comment ---
This article serves as a brief introduction into a complex and controversial topic in life extension science. For decades, anti-oxidants were almost synonymous with anti-aging. Current evidence suggests that the picture is more complex. Yet despite the potential for inefficiency and harm that antioxidants may pose, their role in modulating aging-related health cannot be ignored.
Continue the discussion of individual antioxidants in our supplements forum. 

]]> Sun, 18 Feb 2018 23:36:23 +0000 a2557a7b2e94197ff767970b67041697 Nootropics in human trials (Intro) https://www.longecity.org/forum/page/index2.html/_/articles/nootropics2017 The word "nootropic" derives from the Greek words nous, or "mind", and trepein meaning "to bend or turn". It was first coined by Romanian psychologist and chemist, Corneliu E. Giurgea after synthesizing Piracetam.
For Giurgea a nootropic drug should have the following characteristics:
1. They should enhance learning and memory.
2. They should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).
3. They should protect the brain against various physical or chemical injuries (e.g. barbiturates, scopalamine).
4. They should increase the efficacy of the tonic cortical/subcortical control mechanisms.
5. They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity.

In fact, most drugs commonly labelled as nootropics do not fulfill all of these requirements. Some of the best known (e.g. Adderall, Modafinil) seem to not fulfill any, as discussed later. Instead, other characteristics like (reputed increased alertness, focus or motivation) seem to be key to their popularity.
Because of deviating definitions nootropics are more broadly defined (e.g. in wikipedia) as drugs, supplements, or other substances that improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals. 

Some nootropics from the very common to the :

Caffeine
Caffeine is the world’s most widely used stimulant (Nawrot, et al., 2003). It is used by over 90 % of North Americans every day (Mednick et al., 2008). It is widely used because of its positive effects on mood and alertness (Lorist & Tops, 2003)and vigilance and attention (Lieberman et al., 1987). However, these effects do not seem applicable / transferable to motor learning and verbal memory and are unable to reverse effects of sleep deprivation, with a dose of 200mg in low to moderate users (< than 2 cups a day) (Mednick et al., 2008). It is also shown to be ineffective in higher cognitive tasks involving working memory (Battig et al., 1984). Overall conclusions regarding the relation of caffeine and memory have been mixed. Positive effects might stem from caffeine withdrawal in high dosage users (Mednick et al., 2008).

Nicotine
With about 1,1 billion smokers worldwide in the year 2015 (WHO 2015) nicotine takes second place as the most widely used stimulant. It was shown that the application of nicotine in non-smoking males enhances performance in continuous performance tasks and therefore is said to improve attention and working-memory (Kumari, et al., 2003), which is in line with other studies suggesting that nicotine affects short-term memory in delayed free recall tasks (Sarah & Fox, 1998)
Another study examined nicotine’s effects on alertness and performance on a covert orienting task were measured. While nicotine decreased overall reaction times in the covert orienting task, there was no change in the validity effect, the reaction time difference between validly and invalidly cued targets. However, nicotine significantly improved both EEG and self-rated measures of alertness. Nicotine seems to increases alertness in non-smokers, with no improvement in spatial attention using a covert orienting task (Griesar et al., 2002). Furthermore Nicotine seems to reduce distraction under low perceptual load by acting as a stimulus filter that prevents irrelevant stimuli entering awareness (Behler et al., 2015).

Methylphenidate/ Ritalin
Most college students I know will immediately think of Ritalin or Modafinil if they are asked to name a cognitive enhancer. Studies have found that 4.1% to 10.8% of college students in the US reported using prescription stimulants non-medically during the past year (Garnier-Dykstra, et al., 2012).
Methylphenidate (MPH - common brand name ‘Ritalin’) is used in treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Most studies focused on the its effects on Attention, Mood, Memory and executive functions. A single dose of MPH showed a positive effect on memory. Repeated doses of MPH had a mood elevating effect but also enhanced anxiety. No statistically significant effect was found in the outcomes attention, mood and executive functions. MPH had no significant effect on sleep-deprived individuals (Repantis et al., 2010). In a 2015 review the authors found some ‘publication bias’, relating to long-term and working memory and conclude that the effect in healthy subject is probably modest overall and that healthy users resort to stimulants to enhance their energy and motivation more than their cognition (Ilieva et al., 2015). 

Modafinil
Modafinil is used in treatment of disorders such as narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea. Most studies focused on its effects on attention, mood, memory, wakefulness and executive functions and motivation. A single dose showed positive effects on attention only. On sleep deprived individuals it was shown to have an impact on executive functions, on memory and wakefulness but there was an insignificant effect on mood and attention (Repantis et al., 2010). A 2012 meta-analysis found that Modafinil was likely effective but criticised the gaps in the literature. (Kelley et al., 2012) 
A recent study on chess players found significantly enhanced performance with Modafinil or Ritalin but only when the players were not under time pressure (Franke et al. 2017). 

Adderall
Mixed Amphetamine Salts also known under the brand Name Adderall became increasingly popular in recent years as an athletic performance enhancer and cognitive enhancer. Like Ritalin, it is also used to treat ADHD and narcolepsy.
Overall effects of Adderall on cognition have been reviewed as very modest, while having a huge effect on perception. It was found to enhance performance in word recall, embedded figures and Raven's Progressive Matrices, but only for lower performing individuals (Ilieva et al., 2013). Adderall might also impair creativity in high performing individuals (Farah et al., 2009).

L-theanine & Caffeine
L- theanine is primarily found in plants (e.g. in the leaves of green and black tea) and fungus. Results evidently demonstrated that L-theanine clearly has a pronounced effect on attention performance and reaction time response in normal healthy subjects susceptible to having high anxiety (Higashiyama et al., 2011).
A dose of L-theanine equivalent to eight cups of black tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. The combination of Theanine and caffeine seem to have additive effects on attention in high doses (Kahathuduwa et al.,2016).
Studies suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task (Giesbrecht 2010).

Bacopa Monnieri
Bacopa Monnieri is an herb which has been used in Ayurvedic medicine for centuries. Bacopa's primary mechanism of action is still unclear, it seems to be an anti-oxidant, a weak acetylcholinesterase inhibitor and a cerebral blood flow activator (Aguiar & Borowski , 2013).
There is some evidence to suggest that Bacopa Monnieri improves memory with little evidence of enhancement in any other cognitive domains (Pase et al., 2012).

Piracetam
Closing the circle to the beginning of this short introduction to the topic: Giurgea first coined the term "nootropic" when he synthesized Piracetam in 1964. Since it is not approved by the US FDA, it is primarily used in Europe, Asia, and South America. It is commonly prescribed for cognitive impairment and dementia in several countries of Europe. Research suggests that Piracetam might also have a positive effect on healthy individuals. Subjects were given 3×4 capsules at 400 mg per day, in a double blind study. Each subject learned series of words presented as stimuli upon a memory drum. No effects were observed after 7 days but after 14 days verbal learning had significantly increased (Dimond & Brouwers, 1976). It might also be beneficial for cognitive decline associated with age. Aging subjects did significantly better in a computerized perceptual-motor tasks when on piracetam than on a placebo. (Mindus et al. 1976). While these old studies may not be that reliable, it is still held that Piracetam's “efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia. While high doses are sometimes necessary, piracetam is well tolerated” (Winblad, 2005). Since Piracetam was first synthesized many structurally similar compounds have emerged. These so called Racetams have poorly understood mechanisms of action; however, piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems (Gualtieri et al., 2002).


This article is solely for information purposes, not a substitute for professional medical or dietary advice. 
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* Mednick, S. C., Cai, D. J., Kanady, J., & Drummond, S. P. (2008). Comparing the benefits of Caffeine,Naps and Placebo on Verbal, Motor and Perceptual Memory. Behavioural Brain Research, 79–86.
* Mindus , P., Cronholm , B., Levander , S. E., & Schalling , D. (1976). Piracetam-induced improvement of mental performance. A controlled study on normally aging individuals. Acta Psychiatrica Scandinavia, 150-160.
* Nawrot, P., Jordan, S., Eastwood , J., Rotstein , J., Hugenholtz, A., & Feeley, M. (2003). Effects of caffeine on human health. Food Additives & Contaminants, 1-30.
* Pase, M. P., Kean , J., Sarris , J., Neale , C., Scholey , A. B., & Stough , C. (2012). The cognitive enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. Journal of Alternative Complementary Medicine, 647-652.
* Repantis , D., Schlattmann , P., Laisney , O., & Heuser, I. (2010). Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacological Research, 187-206.
* Sarah , P., & Fox, P. (1998). An investigation into the effects of nicotine gum on short-term memory.Psychopharmacology, 429-433.
* WHO (2015). WHO global report on trends in tobacco smoking 2000-2025. WHO Library Cataloguing-in Publication Data .
* Winblad, B. (2005). Piracetam: a review of pharmacological properties and clinical uses. CNS Drug reviews, 169-182.

]]> Sat, 09 Sep 2017 13:57:38 +0000 9872ed9fc22fc182d371c3e9ed316094 Aging theories: Is there a unifying factor in a... https://www.longecity.org/forum/page/index2.html/_/articles/agingtheories2017a When Darwin’s theory of evolution by natural selection was established, biologists were puzzled by the existence of senescence and aging among all organisms. Why did the evolutionary pressure not produce immortal species? They concluded that even the power of evolution has its limitations. It took almost hundred years to reach the idea that mortal individuals may be preferred by nature for following reasons — the genes resulting in advantage in early life might cause damage in late life, and the reproduction starts as soon as possible. Around the middle of twentieth century, there finally was a framework for the gerontological research conduced in the following decades — the first evolutionary theories of aging (Gavrilov & Gavrilova, 2002). 
There are two major groups of theories aiming to explain the mechanism of aging, so-called programmed and error theories. The programmed ones are based on the senescence-causing nature of certain genes (these are also called evolutionary theories), hormones or the immune system. Error theories claim that we age because of general damage caused by cell weariness, metabolic rate, cross-linked proteins, free radicals or somatic DNA changes (Jin, 2010).
The beauty of various aging theories is that most of them are not mutually exclusive. We can see that newer theories do not necessarily oppose the old ones, but rather shed more light and offer more in-depth views on the process of senescence.
The pioneering idea from 1882 was Weismanns’s theory of programmed death (also called wear-and-tear theory) claiming something like apoptosis of the multicellular organism. Although disproved by experiments, his theoretical explanation of the mechanism predicted the discovery of Hayflick limit (Gavrilov & Gavrilova, 2002). According to Weismann’s first conception, nature priorities young individuals over elderly because of limited resources. Pearl stated his ‘rate of living’ theory of aging in 1928, although the idea comes from Rubner who, in 1908, suggested that every organism has limited amount of metabolic energy and therefore its age depends on the rate of metabolism which correlates with organism’s size (Pearl, 1928). Most consider the rate of living theory to be flawed (Lints, 1989; de Magalhaes, Costa, & Church, 2007; Vaanholt, Daan, Schubert, & Visser, 2009).
A few decades later, the following evolutionary models have emerged: Medawar’s hypothesis of mutation accumulation proposes that aging is a by-product of natural selection — genes causing senescence in later stadium of life cannot be eliminated because the genetic information was most likely already transferred to successors by individuals in their early adulthood (Gavrilov & Gavrilova, 2002). This theory from 1952 is considered the first modern theory of aging. Charlesworth confronted Medawar’s model with a discovery of late-life mortality plateaus and in 1994 presented so-called modified mutation accumulation theory (Charlesworth, 2001; Ljubuncic & Reznick, 2009). In his antagonistic pleiotropy theory (also called ‘pay later’ theory), Williams in 1957 expressed the idea that even the same genes which cause trouble at advanced age may be advantageous in earlier stages of life, and therefore be not only tolerated, but even preferred by natural selection (Gavrilov & Gavrilova, 2002). In 1979, Kirkwood extended this theory to the disposable soma theory — organisms may save energy by reducing accuracy in cells metabolism and invest it in faster development and reproduction (Kirkwood & Holliday, 1979). This is the last one of famous, genes-orientated evolutionary models.
The following can be classified as programmed theories: The neuroendocrine theory proposed in 1954 by Dilman says that the main cause of aging is a loss of receptor sensitivity of the hypothalamus over time, and therefore its control of adequate production of hormones declines which leads to ineffectiveness and lower hormone levels in organism. It is an attempt to explain a high occurrence of degenerative diseases in late age (“Neuroendocrine Theory of Aging: Chapter 1,” 1999). Research on hormonal signaling pathways confirms that hormone levels have at least a partial role in determining longevity (van Heemst et al., 2005). In 1964, Walford suggested his immunologic theory of aging — due to increasing diversity of cells, the immune system looses its efficiency with age which leads to insufficient responses against pathogens as well as to autoimmune reactions against self proteins (Walford, 1964). 
All following attempts to explain the mechanism behind a process of aging are usually called error or damage theories. Bjorksten’s "crosslinkage theory" says that proteins become linked together in presence of certain crosslinking agents, and after some time, accumulation of these molecular aggregates causes decline in tissue functions. This theory from 1942 is no longer popular (Bjorksten, 1968). Later research has showed that advanced glycation end products (AGEs) accumulate in collagen and lead to outcomes predicted by Bjorksten (Verzijl et al., 2002; Aronson, 2003). 
These days very popular among researchers and public, the free radical theory was suggested by Harman in 1956. His idea was that the occurrence of free radicals, or reactive oxygen species naturally produced in living organisms, leads to macromolecular damage which accumulates and causes physiological changes known as senescence (Harman, 2009). Later he suggested the reactive oxygen species formation takes place mainly in mitochondria which causes a decline in important mitochondrial functions (Harman, 1972). Because of the theory’s popularity, various extensions of Harman’s model were created, usually considering different sites as a main target of free radicals. 
Failla’s somatic mutation theory from 1958 posits that increasing number of mutations of genetic material causes a decrease in cellular, organ and body functions (Failla, 1958; Gensler & Bernstein, 1981; Kennedy, Loeb, & Herr, 2012). The theory received a lot of criticism in previous decades (Vijg, 2000). Kaya, Lobanov and Gladyshev (2015) investigated aging in yeast and failed to find evidence in support of Failla’s thesis. 
Orgel proposed his error catastrophe theory in 1963. He saw the cause of aging in accumulation of malfunctioning proteins coming from errors during protein translation (Orgel, 1963). This theory never gained popularity and was soon disproved (Gershon & Gershon, 1976). 
Alexander in 1967 extended Failla’s theory by hypothesizing that DNA damage instead of mutation is the cause of aging (Alexander, 1967). These days, this version called "somatic DNA damage theory of aging" is more often used by scientists (Freitas & de Magalhaes, 2011; Soares et al., 2014). Evidence suggests that more damage happens in mitochondrial DNA than in nuclear DNA (Ames, 2009).
In 2002, Brunk and Terman published the mitochondrial-lysosomal axis theory. It states that defective macromolecules derived from mitochondria undergo further changes in lysosomes to become lipofuscin inclusions. These end products decrease cell’s autophagocytotic capacity which leads to more mitochondrial defects (Brunk & Terman, 2002). 
Zs.-Nagy’s "membrane hypothesis" focuses on a decline of mitochondrial functions due to lessened membrane permeability caused by residual heat coming from nerve signals as well as by reactive oxygen species (Zs.-Nagy, 2014). 
Recent versions of damage theories claim that free radicals are only one kind of senescence-causing by products of metabolism but the real initiator of all the inevitable damage is biological imperfectness. In other words, there are always types of damage which lack adequate repair mechanisms in organism and the most severe source of errors depends on actual conditions (Gladyshev, 2013; Gladyshev, 2014). This idea comes from the "reliability theory", which focuses on systems failure in machines (Gavrilov & Gavrilova, 2001). In spite of many research programs and lots of scientists involved, the unifying factor in aging is at the moment still unknown.

References



The above is a short perspective by Vit Zemanek. Continue the discussion and analysis on LongeCity's long-running AGING THEORIES forum.

]]> Sun, 20 Aug 2017 18:04:47 +0000 eecca5b6365d9607ee5a9d336962c534 Geroprotector Review: Rapamycin and other mTOR... https://www.longecity.org/forum/page/index2.html/_/articles/rapamycin2017 Sven Bulterijs continues his discussion of prominent compounds with potential life extension efficacy by looking not just at rapamycin but also at its target, the mTOR pathway, which has likely a key role in mediating lifespan. ⇒ read the article in "Sven's Science Corner" blog

]]> Tue, 18 Jul 2017 21:03:16 +0000 6cdd60ea0045eb7a6ec44c54d29ed402 Metformin - a geroprotector? https://www.longecity.org/forum/page/index2.html/_/articles/metformin2017 Sven Bulterijs first discussed the potential utility of anti-diabetic substance metformin six years ago on LongeCity. Now Sven returns to the topic with a comprehensive and thoughtful discussion of the recent findings and further background information ⇒ read the article in "Sven's Science Corner" blog

]]> Fri, 19 May 2017 19:12:06 +0000 cedebb6e872f539bef8c3f919874e9d7 Aschwin de Wolf: Cryonics https://www.longecity.org/forum/page/index2.html/_/articles/aschwincryonicsfeb2017 Interview with Aschwin de Wolf (February, 2017)



A de Wolf PictureAschwin de Wolf    is the CEO of Advanced Neural Biosciences, a neural cryobiology research company in Portland, Oregon. Originally from the Netherlands, Aschwin has extensive knowledge as a writer, researcher, consultant and in project management. He worked as the CFO for Suspended Animation Inc., is a co-founder of the Institute for Evidence-Based Cryonics, and edits Alcor’s 'Cryonics' magazine.


The interview was conducted by Sven Bulterijs

1. How has the cryopreservation procedure evolved since the first human was placed in cryostasis?

AdW: The most important element in the progress of cryopreservation procedures in cryonics is the progressive elimination of ice formation. When cryonics started, patients were often cryopreserved without any cryoprotection or very low concentrations of cryoprotectant. In the 1980’s and 1990’s organizations such as Alcor started adapting mainstream perfusion technologies to introduce high concentrations of cryoprotectants (such as glycerol) to mitigate ice formation. In 2000 Alcor formally introduced vitrification with the aim of eliminating freezing altogether.


2. Have changes in the procedure over the last decades (composition of cryoprotectant, rate of cooling, etc.) lead to a measurable decrease in the damage that occurs during vitrification?

AdW: Yes. The elimination of ice formation, which can be achieved in good cases, removes one major form of mechanical damage in the cryopreserved brain. One very attractive feature of a low-toxicity vitrification agent like M22 is that it does not require rapid cooling to prevent ice formation. Under good circumstances (no prior ischemia) it can also be used in whole-body patients without edema – a problem that seemed to plague prior DMSO-based cryoprotectants in cryonics. Elimination of ice formation and reduced toxicity has substantially reduced the degree of damage associated with cryopreservation.


3. Which foreseeable advances in the field of cryobiology do you believe will lead to improvements in cryonics?

AdW: I foresee further advances in two areas; a more detailed understanding of the nature of cryoprotectant toxicity and the design of brain-optimized cryoprotectants. Cryoprotectant toxicity is currently the most formidable obstacle preventing reversible cryopreservation of complex mammalian organs. With the exception of the work of Dr. Greg Fahy and his colleagues at 21st Century Medicine, it is rather surprising how little theoretical and experimental research has been done to illuminate the mechanisms of cryoprotectant toxicity. It is also increasingly recognized that the poor penetration of cryoprotectants across the blood-brain barrier causes dehydration of the brain. We need to develop brain-optimized vitrification solutions and/or identify better methods to deliver cryoprotectants to the brain without such significant changes in brain volume. Resolving these two issues will bring us much closer to reversible brain cryopreservation.


4. People have experimented in the past with a wide variety of antioxidants, chelators and membrane stabilizing molecules to reduce the damage to the body at the start of the procedure (so just after legal pronunciation of death). Have any of these been successful and are people still trying to find such substances to reduce damage at the early moments of the procedure?

AdW: I think it is important to recognize that all these anti-ischemia interventions are more important when there is a delay between pronouncement of death and the start of cryonics procedures. If there is a rapid and smooth transition between the two, immediate restoration of circulation, rapid induction of hypothermia, and aggressive anti-thrombotic therapy should be sufficient to maintain cerebral viability of the brain by contemporary medical criteria.

Our lab Advanced Neural Biosciences, has collaborated with Alcor to conduct a rather comprehensive study of the effects of Alcor’s stabilization medications protocol and the most robust finding in this research has been that the combination of heparin and citrate allows for ice-free cryopreservation of the brain when these compounds are administered immediately after pronouncement of legal death. When medication administration is delayed by more than 15 minutes, things get more challenging and breakdown of the blood brain barrier and whole-body edema during cryoprotective perfusion is a typical outcome. Preventing edema of the patient during cryoprotective perfusion after prolonged periods of ischemia remains one of the most difficult research challenges to solve.


5. What evidence is there that the brain is not damaged by the cryopreservation process to such an extent that the information in it may be lost forever?

AdW: I can answer this in two ways. To start with, if we can eliminate ice formation in the brain, the damage associated with cryoprotectant toxicity is assumed to be mostly of a biochemical nature (i.e. denatured proteins) and does not alter the ultrastructure of the brain in a way that precludes inferring the original state. Cryoprotectant-induced dehydration of the brain is a little more of a wild card because we do not have much detailed information about the kind of ultrastructural changes associated with it. Hence, the priority to avoid the brain shrinking that is routinely observed in “good” cases. Ultimately, our incomplete knowledge of the neuroanatomical basis of identity, and about the exact capabilities and limits of future medicine, prompt us to be agnostic about the degree of damage that is still compatible with meaningful revival. Advocates of cryonics are sometimes accused of being too optimistic about future science, but perhaps skeptics are too pessimistic.


6. Do any changes take place in the bodies during cryogenic storage? And if such changes take place does that mean that the chance on successful reanimation will decrease over time?

AdW: No. To our knowledge (which is based on cryobiological studies and theoretical calculations), deterioration of patients stored at cryogenic temperatures should be non-existent or negligible. Things get a little bit more complicated when we store patients at intermediate temperatures (intermediate temperature storage or “ITS”) instead of liquid nitrogen temperatures. It has been suggested that nucleation may still occur slightly below the temperature where the vitrification solution turns into a glass (-123 degrees Celsius). At that temperature, however, nucleation does not translate into ice formation but it might create more challenging repair and revival scenarios.


7. Do you have any hypotheses on how the cryoprotectant could be removed from the body during the reanimation procedure and how hypoxic injury during this removal procedure could be prevented?

AdW: Roughly speaking, there are two distinct approaches to the repair and revival of cryonics patients. In the vision of researchers such as Robert Freitas and Ralph Merkle, a mature form of mechanical nanotechnology will be used to conduct the initial stages of repair and cryoprotectant removal at cryogenic temperatures. If this vision of nanotechnology is plausible, cryoprotectant can be removed while providing (local) metabolic and structural support to prevent damage or freezing. An alternative vision of nanomedicine will involve the use of biological repair machines such as modified viruses or modified white blood cells that operate using conventional diffusion-driven chemistry rather than molecular mechanical nanotechnology. Repair is more challenging in this biological scenario because tissue first needs to be warmed to temperatures at which the cryoprotectant solution inside cells and tissue becomes liquid. This risks movement of damaged structures, possible growth of ice, and cryoprotectant toxicity accumulation occurring at the same time as repairs are being made. To my knowledge, there have not been many serious studies of how such devices can operate and navigate through these problems at the same time.


8. What is in your opinion the chance that a cryopreserved person would be revived in a human state versus an uploaded version as uploading may be a way around irreparable cryopreservation damage?

AdW: I am personally partial to the idea of doing molecular level repairs through mechanical or biological nanomedicine because it does not require a paradigm shift in how we think about the nature of identity and consciousness. The feasibility of mind uploading is ultimately about the feasibility of substrate-independent minds and I do not think that the debates surrounding this can be resolved prior to empirical verification. In my opinion, the proposal of cryonics is intrinsically linked to the idea that the non-damaged state of the brain can be inferred from the damaged state through some form of molecular medicine. Many people feel quite comfortable with reconstruction of ancient DNA or forensic inference, but when it comes to cryonics, people tend to treat the brain in a somewhat superstitious fashion and cannot imagine forms of medicine that operate with molecular precision.


9. Even if reanimation after cryopreservation becomes technologically possible, what would make you believe that future generations will spend the money and resources on reanimating all people from cryostasis rather than just one or a few as an experiment?

AdW: This is an easier question to answer because it is the aim of cryonics organizations themselves to resuscitate their patients, not the general public, or curious scientists. The Alcor Life Extension Foundation parks a rather substantial portion of the cryopreservation fees in a so-called Patient Care Trust that should permit patients to be maintained in perpetuity (in theory) and revived when the technologies are available and affordable. Of course, if the technologies to revive cryonics patients will come to fruition, it seems quite reasonable to assume that the legal status of cryonics patients will also change and patients at cryonics organizations will be considered living people in a critical condition.


10. Do you see a mutual exchange of techniques and knowledge between the human cryopreservation field and the field of storing human biological samples (e.g. sperm, fertilized eggs, etc.)?

AdW: Yes. As a general rule, the obstacles that are faced by researchers of storage of biological samples and complex mammalian organs are the same obstacles that need to be overcome for reversible cryopreservation of humans (medical biostasis) as well. Any insights into the mechanisms of cryoprotectant toxicity, chilling injury, and the effects of cryopreservation on gene expression are of great relevance to cryonics. I should add, however, that I expect this exchange to be mutually beneficial. One of the least recognized and appreciated aspects about the field of cryonics is that researchers sympathetic to the idea of human cryopreservation have made meaningful and innovative contributions to mainstream fields such as cryobiology and cerebral resuscitation.


11. Cryogenic storage of genetic mutants in laboratory animals could reduce the cost of biomedical research. This is already a common procedure in the roundworm C. elegans. Are you aware of any research taking place that tries to expand cryogenic storage to other model organisms?

AdW: Natasha Vita-More, who conducted recent studies on the effects of vitrification on memory in C. elegans, has suggested that the next step would be a slightly more complex organism such as the Greenland Woolly Bear Caterpillar or the ozobranchid leech. One of the most common suggestions I get is to attempt suspended animation on a mouse or rat. This would definitely provide powerful proof of principle for the feasibility of human suspended animation, but I do not think that the challenges in achieving reversible biostasis in a small mammal are that much smaller than in humans. We would need to overcome the same obstacles: minimizing cryoprotectant toxicity, chilling injury, dehydration of the brain, ischemia during cooling, and cryoprotective perfusion, etc. The majority opinion in cryonics is to solve these individual problems more thoroughly before attempting reversible cryopreservation of a complete animal.


12. In a recent ruling on a 14-year old girl wanting cryonics, a UK judge stated that there is a lack of regulation concerning cryonics. If a government would ask your advice on creating such regulations then what would you tell them?

AdW: I think the first thing I would recommend is that experts (which should include researchers and practitioners of the field) create a protocol to conduct cryonics as a hospital-based, elective, medical procedure. Reviewing the technical requirements and supporting evidence for cryonics will lead to a greater recognition of the need of improved legal protection for cryonics patients. Too often, cryonics is dismissed because people do not understand the conceptual arguments in favor of it, or its multi-disciplinary nature. In particular, the idea of molecular medicine is usually ignored in discussions about the (potential) damage of cryonics procedures. If regulations and protocols are created based on a dispassionate examination of the arguments and evidence in favor of cryonics, I think we do not necessarily need to fear regulation of the field.

]]> Sun, 19 Feb 2017 13:12:14 +0000 4c5bde74a8f110656874902f07378009 Why do some turtles outlive humans? https://www.longecity.org/forum/page/index2.html/_/articles/turtles (⇒ write for LongeCity )


The oldest human recorded in modernity was Jeanne Louise Calment, she died in the age of 122 years and 164 days [1] .

There are rumors that the oldest tortoise called Adwaita (Aldabra giant tortoise) died in the age of about 250 years [2] or that it was 188-year-old radiated tortoise named Tui Malila [3] , or that the highest verified age of 177 years had Galapagos giant tortoise Harriet [4] . The oldest currently living turtle is considered to be Jonathan (Seychelles giant tortoise), estimated to be over 180 years old these days [5] . Although all aforementioned numbers are estimations, it seems these turtles were older than human supercentenarians.

All previously mentioned species are terrestrial tortoises, a group with longest lifespans among turtles. The most famous of them, well-researched Galapagos giant tortoise, was observed by Charles Darwin when he was forming his well-known theory of evolution by natural selection [6] . There is only one freshwater turtle known to be able to outlive human, it is the common snapping turtle estimated to live up to more than hundred years [7] . While being considerably less researched, recorded maximal lifespan of sea turtles is usually shorter, not exceeding 80 years, however, it is believed that the green sea turtle can live up to 100 years. [8]

It is a difficult question to answer why these reptiles can outlive us because even to determine the actual age of animals with a long lifespan is complicated – partially due to the fact that it takes such a long time to study. Furthermore, many turtles are endangered species [9] so there may not be as many organisms to hand as needed for proper statistics. Nonetheless, we can still claim that turtles are among the most long-living vertebrates on earth [10] . Why?

Firstly, turtles, like all reptiles, benefit from being ectothermic organisms. They do not maintain body temperature and thus save a lot of energy. But that also means they are less flexible: it is crucial for their lifespan to be in natural temperature environment of daily cycles with night-time temperature drop [11] . If they do not live under these conditions in captivity, metabolic pathways change and turtles die much sooner. [12]

Turtles are well-adapted in other ways: their famous shell – the carapace –is good protection against natural predators. Most of hatchling turtles with a soft shell do not survive the first year [13] . A research of natural populations of freshwater turtles showed that only one per cent of them can celebrate the twentieth birthdays, but once the adulthood is reached, mortality rate drops and remains constant throughout the rest of life [14] .

Some turtles can survive under extreme environmental conditions, such as freezing [15] or lack of oxygen for months [16] . They can even undergo hibernation and anaerobic metabolism and therefore deal with hypoxia and anoxia, it was also proposed that the same genes can play a role in longevity itself [17] and also in oxidative stress resistance [18] that further promotes longer life [19] .

Turtle’s bones and shell are used as lactate buffer lowering metabolic acidosis caused by anaerobic glycolysis during the period of lack of oxygen [20] ; [21] Their organism is protected by strong innate immunity compensating slow acquired immune reactions [22] .

Because turtles have very slow metabolism as well as growth, their bodies do not need to deal with excessive metabolic heat and byproducts as mammals [23] . Their natural diet is very simple but also necessary for their longevity. [24]

According to the evolutionary theories, staying alive is less important after menopause. Galapagos giant tortoises achieve sexual maturity late (around the age of up to forty years in the wild, and between twenty and twenty-five years of life in captivity [25] ), then staying fertile until death [26] .

The Hayflick limit is said to determine how many times a cell can divide [27] . The Hayflick limit of Galapagos giant tortoise was said to be about 110 divisions [28] , approximately twice as many as 50 of human cells [29] . Studies in this context have highlighted the importance of telomeres, the protective end sequences of chromosomes, that get shorter with each cell division [30] , can play at least a partially role in life expectancy. It was observed that telomeres in European freshwater turtle’s cells are of the same length in both embryo and adult organism [31] .

Thus, it was believed that turtles are negligibly senescent organisms [32] . In other words, the cells do not age and no age-related diseases appear, which is very different cell behavior than in human bodies [33] and probably the key to any natural longevity. However, evidence now suggests that turtles may not be really negligibly senescent because of observations of survival and reproductive senescence in late age in the painted turtle population [34]

As we can see, turtles have some advantages in the lifespan field. Some of these might inspire researchers to increase lifespans in humans.



References

[1] Oldest person ever. Retrieved January 31, 2017, from http://www.guinnessworldrecords.com/world-records/oldest-person
[2] BBC (2006, March 23). “Clive of India’s” tortoise dies. BBC South Asia. Retrieved from http://news.bbc.co.uk/2/hi/south_asia/4837988.stm
[3] Associated Press (2006, June 26). Tortoise believed to have been owned by Darwin Dies at 176. Fox News. Retrieved from http://www.foxnews.com/story/2006/06/26/tortoise-believed-to-have-been-owned-by-darwin-dies-at-176.html
[4] Galapagos tortoise (Geochelone nigra) longevity, ageing, and life history. Retrieved January 31, 2017, from http://genomics.senescence.info/species/entry.php?species=Geochelone_nigra
[5] Hollins, J. (2012). The world’s most isolated vet? Veterinary Record, 171(2), i–i. doi:10.1136/vr.g7292
[6] Powell, J., & Caccone, A. (2006). Giant tortoises. Current Biology, 16(5), R144–R145. doi:10.1016/j.cub.2006.02.050
[7] Cameron, M. (2008). COSEWIC Assessment and Status Report on the Snapping Turtle Chelydra serpentina in Canada . Retrieved from http://publications.gc.ca/collections/collection_2009/ec/CW69-14-565-2009E.pdf
[8] Green sea turtle (Chelonia mydas) longevity, ageing, and life history. Retrieved January 31, 2017, from http://genomics.senescence.info/species/entry.php?species=Chelonia_mydas
[9] Jacobson, E. R. (1994). Causes of Mortality and Diseases in Tortoises: A Review. Journal of Zoo and Wildlife Medicine, 25(1), 2–17.
[10] Gibbons, J. W. (1987). Why do turtles live so long? BioScience, 37(4), 262–269. doi:10.2307/1310589
[11] Flouris, A. D., & Piantoni, C. (2014). Links between thermoregulation and aging in endotherms and ectotherms. Temperature, 2(1), 73–85. doi:10.4161/23328940.2014.989793
[12] Vadala, N. How Long Do Turtles Live? Retrieved January 31, 2017, from http://www.petmd.com/reptile/care/how-long-do-turtles-live
[13] Stewart, K. R., & Wyneken, J. (2004). Predation risk to loggerhead hatchlings at a high-density nesting beach in Southeast Florida. Bulletin of Marine Science, 74(2), 325–335.
[14] Gibbons, J. W., & Semlitsch, R. D. (1982). Survivorship and longevity of a long-lived vertebrate species: How long do turtles live? The Journal of Animal Ecology, 51(2), 523. doi:10.2307/3981
[15] Packard, G. C., & Packard, M. J. (2003). Natural freeze-tolerance in hatchling painted turtles? Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 134(2), 233–246. doi:10.1016/s1095-6433(02)00264-7
[16] Milton, S. L., & Prentice, H. M. (2007). Beyond anoxia: The physiology of metabolic downregulation and recovery in the anoxia-tolerant turtle. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 147(2), 277–290. doi:10.1016/j.cbpa.2006.08.041
[17] Shaffer, H. B., Minx, P., Warren, D. E., Shedlock, A. M., Thomson, R. C., Valenzuela, N., … Wilson, R. K. (2013). The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage. Genome Biology, 14(3), R28.doi:10.1186/gb-2013-14-3-r28
[18] Garbarino, V. R., Orr, M. E., Rodriguez, K. A., & Buffenstein, R. (2015). Mechanisms of oxidative stress resistance in the brain: Lessons learned from hypoxia tolerant extremophilic vertebrates. Archives of Biochemistry and Biophysics, 576, 8–16. doi:10.1016/j.abb.2015.01.029
[19] von Zglinicki, T. (2002). Oxidative stress shortens telomeres. Trends in Biochemical Sciences, 27(7), 339–344. doi:10.1016/s0968-0004(02)02110-2
[20] Jackson, D. C. (2000). Living without oxygen: Lessons from the freshwater turtle. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 125(3), 299–315. doi:10.1016/s1095-6433(00)00160-4
[21] Krivoruchko & Storey, 2010).
[22] Sandmeier, F. C., Tracy, C. R., Dupre, S., & Hunter, K. (2012). A trade-off between natural and acquired antibody production in a reptile: Implications for long-term resistance to disease. Biology Open, 1(11), 1078–1082. doi:10.1242/bio.20122527
[23] Bilinski, T., Paszkiewicz, T., & Zadrag-Tecza, R. (2015). Energy excess is the main cause of accelerated aging of mammals. Oncotarget, 6(15), 12909–12919. doi:10.18632/oncotarget.4271
[24] Casares, M., Honegger, R. E., & Rubel, A. (1995). Management of giant tortoises Geochelone elephantopus and Geochelone gigantean at Zurich Zoological gardens. International Zoo Yearbook, 34(1), 135–143. doi:10.1111/j.1748-1090.1995.tb00671.x
[25] Global, S. D. Z. (2010). Galapagos tortoise fact sheet. Retrieved January 31, 2017, from http://library.sandiegozoo.org/factsheets/galapagos_tortoise/tortoise.htm
[26] Curtin, A. J., Zug, G. R., & Spotila, J. R. (2009). Longevity and growth strategies of the desert tortoise (Gopherus agassizii) in two American deserts. Journal of Arid Environments, 73(4-5), 463–471. doi:10.1016/j.jaridenv.2008.11.011
[27] Hayflick, L. (1965). The limited in vitro lifetime of human diploid cell strains. Experimental Cell Research, 37(3), 614–636. doi:10.1016/0014-4827(65)90211-9
[28] Goldstein, S. (1974). Aging in vitro. Experimental Cell Research, 83(2), 297–302. doi:10.1016/0014-4827(74)90342-5
[29] Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental Cell Research, 25(3), 585–621. doi:10.1016/0014-4827(61)90192-6
[30] Harley, C. B., Futcher, A. B., & Greider, C. W. (1990). Telomeres shorten during ageing of human fibroblasts. Nature, 345(6274), 458–460. doi:10.1038/345458a0
[31] Girondot, M., & Garcia, J. (1999). Senescence and longevity in turtles: What telomeres tell us. 9th extraordinary meeting of the societas Europaea Herpetologica, 1, 25–29. Retrieved from //www.researchgate.net/publication/252290006_Senescence_and_longevity_in_turtles_What_telomeres_tell_us
[32] Miller, J. K. (2001). Escaping senescence: Demographic data from the three-toed box turtle (Terrapene carolina triunguis). Experimental Gerontology, 36(4-6), 829–832. doi:10.1016/s0531-5565(00)00243-6
[33] Schächter, F., Cohen, D., & Kirkwood, T. (1993). Prospects for the genetics of human longevity. Human Genetics, 91(6), . doi:10.1007/bf00205074
[34] Warner, D. A., Miller, D. A. W., Bronikowski, A. M., & Janzen, F. J. (2016). Decades of field data reveal that turtles senesce in the wild. Proceedings of the National Academy of Sciences, 113(23), 6502–6507. doi:10.1073/pnas.1600035113

]]> Thu, 09 Feb 2017 00:45:06 +0000 fc221309746013ac554571fbd180e1c8 CellAge fundraiser support https://www.longecity.org/forum/page/index2.html/_/feature/cellage-fundraiser-support-r80

]]> Sun, 29 Jan 2017 22:45:36 +0000 045117b0e0a11a242b9765e79cbf113f Article: Gut microbiome in health and aging https://www.longecity.org/forum/page/index2.html/_/articles/microbiome

As part of his new column "Sven's Science Corner" Sven Bulterijs discusses novel insights into the crucial role gut bacteria seem to play in health, disease and aging. ⇒ read the article in "Sven's Science Corner" blog

]]> Tue, 10 Jan 2017 18:01:50 +0000 8f53295a73878494e9bc8dd6c3c7104f Supplement Review: Nicotinamide Riboside https://www.longecity.org/forum/page/index2.html/_/articles/reviewnicotinamideriboside



]]> Sat, 19 Nov 2016 10:04:10 +0000 8f85517967795eeef66c225f7883bdcb review: LongeCity Crowdsourced Initiatives https://www.longecity.org/forum/page/index2.html/_/articles/crowdsourced-initiatives

'Crowdsourcing' information is at the heart of how LongeCity operates.
Consequently, almost all of Longecity's initiatives are community-led.
Some examples of projects we have crowdsourced in the past: 
BOOK: The Scientific Conquest of Death: Essays on Infinite Lifespans
[2004] Commissioned and edited by the LongeCity community, this book brings together perspectives from scientists, doctors and philosophers to share their perspective on Longecity’s mission..
FILM: Exploring Life Extension 
[2005] Featuring an introduction into the scope on Longecity’s mission, through interviews with scientists and philosophers, this feature length documentary was entirely produced, filmed and edited by LongeCity volunteers. 
Cryonics Hardship Charity
[2008, 2010] The LongeCity community supported dying individuals who were unable to afford a cryonic suspension as last resort.
Crowdsourced PRODUCT: Life extension multivitamin
[2010-11]. The unique formulation VIMMORTAL for a multivitamin supplement was invented, refined, developed and licensed entirely from the Longecity community forums and made available for sale in  [Forum Group] 
Folding @Home 
[2010-11] When Stanford launched the first ‘distributed computing’ project with a life science angle, LongeCity recognised the outreach potential of such initiatives and sponsored a friendly competition to bring more contributors on board and to accelerate the project. [Forum Group]
“Soil for SENS”
 [2005-6] Lead: J.Schloendorn. John turned to the LongeCity community and beyond in search for exotic soil samples that might contain microbes which could help to break down age-related protein build-up in humans. 
[ forum thread  / publication] 

Mouse Studies @Home
[2013] Lead: AgeVivo. Longecity supported the idea of setting up a network of “citizen scientists” looking to analyse the diet of their pet mice for life extension benefits. 

‘Fight Aging’ for SENS
[2013-15] Lead: Reason. While not its main platform, Longecity has always showcased the phenomenally successful ‘Fight Aging’ fundraiser in support of the SENS foundation co-ordinated by our former director Reason and other partners. 
- - -
  In addition to these community initiatives, Longecity has also 
⇒ taken the crowdfunding approach to research projects. 		  

]]> Tue, 19 Jul 2016 03:34:49 +0000 96da2f590cd7246bbde0051047b0d6f7 review: LongeCity Crowdfunded Research Projects https://www.longecity.org/forum/page/index2.html/_/articles/crowdsourced-science

Longecity’s approach to supporting scientific research has always been characterized by small-scale, high-impact projects sourced and steered by and in connection with its community. Years before ‘crowdfunding’ and ‘citizen science’ became well known concepts they were practiced at LongeCity. 

Some examples of SCIENCE projects we have crowdsourced in the past: 
“Laser ablation of lipofuscin”
[2009] Lead: N.Schooler (SENS/private). An attempt to use medical lasers to eliminate Alzheimer plaques, this was an early venture in Longecity crowdfunding. While results were not of satisfactory robustness, this project paved the way towards LongeCity taking a planned approach to quality control in community crowdfunding science. [More info]
“Mitochondrial uncoupling” 
[2010] Lead: Dr. J.Gruber (Singapore). Modulation of the incomplete coupling of electron transfer to ATP synthesis across the mitochondrial membrane has been proposed as a mechanism to slow aging. The project investigated this hypothesis in worms. 
[Follow-up interview] 
“Adult stem cells versus Alzheimer's” 
[2011] Lead: Dr. A.Stolzing (Germany). Aiming to use adult stem cells in the fight against age-related neurodegeneration such as Alzheimer's disease. Perhaps the most ambitious LongeCity funded project to date. [Publication]
“Modelling cryoprotectant toxicity”
[2012] Lead: Dr. JP de Magalhães (UK). The innate toxicity of compounds used to protect against freezing damage limits their use for advancing the science of medical biostasis. Longecity crowdfunding helped generate new insights from gene expression profiling of endothelial cells exposed to ethylene glycol, thus helping to reveal molecular signatures helpful for future experiments on cryoprotectant toxicity [Publication] 
“Mitochondria gene therapy” 
[2013] Lead: Dr. M.O’Connor (SENS). Another perspective at the crucial role of mitochondria in aging, this project supported research into rejuvenating these ‘power plants’ of the cell. $21K was mobilized and lead directly to a much larger follow-up project 
“Buckyballs & cancer” 
[2014] Lead: Dr. K.Moody (Ichor), the Longecity community got very intrigued about a research paper reporting to extend mouse lifespan with nanosize C60 ‘buckyballs’. Via crowdsourcing we promoted further independent investigation into C60 effects  which, as a side effect also prompted some interesting vendor testing data. 
- - -
  In addition to these specific research projects, LongeCity has
 ⇒ supported students via small grants,  

⇒ established a research partnership and support strategy
and
⇒ taken the same crowdsourcing approach to other community initiatives. 		  

]]> Tue, 19 Jul 2016 02:05:23 +0000 38af86134b65d0f10fe33d30dd76442e LongeCity Affiliate Labs https://www.longecity.org/forum/page/index2.html/_/feature/labs The Longecity “Affiliate Labs” are small, research-focused enterprises or independent academic research groups led by a scientists with strong ties to the Longecity community and a proven track record of commitment to scientific inquiry directly relevant to the Longecity mission.
These leaders and their colleagues are not just trailblazers in advancing important areas of regenerative and rejuvenation research, but also incredibly helpful when there is a community need for peer review, when providing advice and training to a young scientist, and in providing the expertise and tools to test the novel, controversial, or promising scientific leads sourced from the Longecity community and beyond.

Community Funding
There is a small support fund that the labs can draw on to flexibly support their research activities. While not a substitute for private investment and public sector grants, the ability to flexibly ‘just try’ out a new idea without needing to ‘pitch’ in lengthy proposals can be an invaluable accelerator to research progress. All Affiliates have an active link to the Longecity community, so there is a level of accountability and responsiveness beyond anything encountered in ‘traditional’ research donations.
By donating to the Affiliate Labs fund, Members can be assured that every penny goes directly to an expert personally and professionally committed to making a difference in the scientific conquest of death.
Donate HERE

Current Affiliate Labs
- Alexandra Stolzing, Loughborough University, UK & Leipzig University, Germany.
- James Clement - Betterhumans, USA
- João Pedro de Magalhães, University of Liverpool, UK
- John Schloendorn – Gene&Cell Technologies, USA
- Kelsey Moody, Ichor Therapeutics, USA.
- Kevin Perrott – Buck Institute, USA
- Matthew O’Connor – SENS Foundation, USA

]]> Mon, 20 Jun 2016 01:16:58 +0000 82161242827b703e6acf9c726942a1e4 <![CDATA[8 Reasons to reach out to 'the public']]> https://www.longecity.org/forum/page/index2.html/_/feature/8-reasons-to-reach-out-to-the-public-r74

While the idea that drastic life extension may be an option for humankind in the future has been encountered by many through the media and fiction, the vast majority of the public do not grasp whether and how this could realistically apply to them or their loved ones. 
 
Some argue that since life is an universally desirable good and age-related suffering and death universally feared and avoided, ‘public perception’ is something that will take care of itself. If anything, the inherent attractiveness of the concept will always guarantee media interest perhaps even to the point of generating unwarranted hype and the empty promises that have been the bane of the scientific life extension movement for centuries. 
 
Others argue, with great conviction, that public perception and ‘marketing a life extension movement’ should be a prime objective. Here is a list of eight reasons why:  
 
1. Broaden the pool of ideas. Generally, the more minds are altered to and focused towards a common objective, the greater the chance than innovative or groundbreaking ideas will be generated. If Life Extension is a more broadly known, accepted and prestigious topic of interest, more bright minds will be attracted to it.  
 
2. Increase public sector funding and donations. As businesses tend to fund research only when profitability is close it often falls to the public sector and philanthropists to fund the "starter end" of research that will eventually lead to usable products which business will then want to take up. 
 
3. Reduce opposition.  There is an element of ‘shock’ associated with the concept that aging and death may not be inevitable which can lead to denial or impatient dismissal. Visceral or ideological opposition to life extension translates into less government funding, less scientific interest, less favorable laws and less industry support especially if there is no widely established counter-position.   
 
4. Improve regulation.  Whether we are thinking about laws allowing or prohibiting life extension treatments in general, or the speed and efficiency at which the FDA similar entities conduct their reviews, the support of government agencies is important at every stage of the process of getting treatments to the public. Responsive regulation can be generated through public pressure and media attention. 
 
5. Focus corporate interests towards effective treatments.  Only if there is a clear and well-informed demand for proven and validated treatments will effective products become more profitable to the industry than ineffective ‘snake oil’.
 
6. Build economies of scale.  Given the urgent need for life extension treatments for many people there is an interest in helping to bring costs down as soon as possible. If pent-up public demand becomes more clearly visible, consideration of scale-up will become a part of more business plans and healthcare reforms. 
 
7. Improve public health.  A focus on life extension often comes with increased health consciousness. Prevention is better and cheaper than cures and if more people participate in a wider programme of health-conscious living, this is likely to bring overall healthcare costs down.
 
8. Reduce social unrest and disruption.  Even once society accepts the concept of life extension and associated treatments there will still be people who are unwilling or unable to participate. Moreover, extended lifespans will affect society profoundly. Careful public engagement ensures that social unrest and discrimination can be minimised.  
 
If at least one of these reasons makes sense to you, then you may want to think about how you could help ‘connect’ the LongeCity’s mission with others. Generally, the ‘self-multiplying’ effect of outreach should not be underestimated. People act as role models and influencers of their peers. Beyond all media spin, if a person acts and speaks with conviction, others will take note; and if people realize that their friends and family members could live longer they will be more willing to engage in the idea themselves.  
 
 
-- 
This article is based on an original drafted by Sanhar in response to a LongeCity tender.

]]> Sun, 08 Mar 2015 23:35:01 +0000 bf8229696f7a3bb4700cfddef19fa23f Assessing the effects of c60 on human cancer pr... https://www.longecity.org/forum/page/index2.html/_/articles/sci2014b  View attachment: c60re02.png 

 

"Assessing the effects of c60 on human cancer proliferation in vivo"

is led by life-extension trailblazer Kelsey Moody. It is interesting that he turns the attention of his new venture Ichor Therapeutics to the potential health effects of 'buckyballs' - a topic that has received significant attention on LongeCity ever since it was claimed in a scientific report that rats fed on olive oil infused with these structures experience dramatically increased maximal lifespans. (Review here). 
True to it mission, LongeCity hosts the leading international discussion forum on this topic. Previously, the LongeCity community has come together to fund further grassroots research on C60 in mice and these studies are on-going.

Meanwhile though, in keeping with the pioneer spirit often found on the LongeCity forums, reports have come in from people trialing C60 in olive oil on themselves. As Kelsey points out, the long-term safety of this has yet to be established, and this project is particularly interested in whether C60 in olive oil has any cancer-inducing properties. Conversely, it may be the case that the compound has a tumor–suppressing function. 
To investigate this, the team  plans to infuse a total of 25 mice with C60-olive oil of various strengths or with an inert ‘control’ solution, graft a human cancer cell line to the mice and study the results. (Full research proposal here) 
 
If the fundraiser succeeds it will further support the revolutionary notion of stakeholder-oriented, grass-roots science which complements, challenges and enriches academic research at those junctures that the community actually cares about. Moreover and perhaps even more importantly the fundraiser will help to built capacity and community interface at a dedicated life-extension research facility. Already, Ichor has housed an intern on a LongeCity stipend (Report here- Members only). Ultimately, we hope to create a network of such community-friendly labs around the globe, to provide aspiring young scientists
with training and networking and all members with easily accessible sources of expert advice.

LongeCity has facilitated 'crowdfunding' well before many other platforms in use today. This year, we have decided to try to tap into the potential of these external sites, but to add something to the process: This project is the first one to run on an external fundraising page that has received an official ‘stamp of endorsement’ from LongeCity.
The team has mooted the project at LongeCity, submitted for formal peer review and informal members comments and the board looked into the ability of the team to use the donated money responsibly and to deliver success (Internal link here).  In the end, the project received a high rating of 3 stars and LongeCity decided to match each dollar donation from our general funds. And, awesomely, a generous Member immediately stepped forward to match them as well!
 
This means we only need to raise $6.000 via the external crowdfunding page at indigogo. Please give generously and spread the word!

For any queries about the project to Kelsey and the team, please post below.

]]> Mon, 08 Sep 2014 15:12:36 +0000 f7e6c85504ce6e82442c770f7c8606f0 Cryonics Hardship Fund https://www.longecity.org/forum/page/index2.html/_/feature/cryohardshipfund
Cryonics prices vary (an overview can be found on this page maintained by Cryonics expert and LongeCity Advisor Ben Best) but it is affordable to nearly everyone via life insurance… nearly everyone. A few people who really want cryonics cannot get life insurance: After an accident, LongeCity Member James Swayze found himself quadriplegic and unable to get insurance. The life of LongeCity Member William O’Rights took a turn for the worst when he was diagnosed with aggressive throat cancer after having been suddenly deprived of all funds. Kim Suozzi was 23 and had not yet heard about cryonics when she was diagnosed with terminal brain cancer. Aaron Winborn heard of her case - and cryonics- only when the debilitating effects of Lou Gehrig's Disease had already begun to paralyse him. All these people were eventually offered a cryonics provision through the generous donations of others in our community.
We want to continue this proud tradition, looking out for those who share our common dream in unlimited lifespans, in the shadow of imminent death and despair.

However, this needs to be done carefully. It cannot be stressed enough that cryonics is affordable to most people if they only have the foresight to act early and arrange affordable life insurance. This element of personal responsibility is at the heart not just of cryonics. If we establish a hardship scheme, it must not create a moral hazard, and incentive to put things off as too unpleasant and complicated to think about until it is too late. Of course, we must also ward against fraud and abuse. An element of careful analysis and due diligence is therefore required, looking into the circumstances of each individual case.

The LongeCity cryonics hardship fund has two purposes:
1) To support a (volunteer based) infrastructure for maintaining the scheme and exercising the due diligence mentioned above
2) When a hardship case has been endorsed by LongeCity, we will use the hardship fund to help to fundraise for that individual by matching further donations. All these donations will go to a dedicated account for that person’s cryopreservation, never to the individual directly.

Applicants to our cryonics hardship fund must
- co-operate fully with LongeCity appointed auditors and reviewers
- genuinely be unable to not fully fund their cryosuspension and not have a reasonable chance of doing so prior to their likely death
- help to fundraise for their cause and help raise public awareness for cryonics

In the past, we have partnered with our friend in the Venturist community on cryonic hardship cases. We hoping to do so again on future occasions.



Click HERE to make a contribution to the fund

To apply email the full details of your case: contact@longecity.org]]> Fri, 18 Jul 2014 23:26:34 +0000 3636638817772e42b59d74cff571fbb3