The good folks from Lifespan.io have asked whether LongeCity would sponsor this event as we have in the past. 

The sponsorship would come with a free ticket, but unfortunately, Mind has reported from other conferences cannot attend. 

Is there another LongeCity member whom would like to go?

- You need to be a member (but if this entices you to join for the first time, that's fine) 

- You promise to write a conference report and share it on this forum 

- If we manage to send you some LC flyers, you promise to hand them out (or at least put them somewhere where people can take them)

If you are interested, please use the contact form ("small grants" tab) ASAP 

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On May 7, a study was posted on bioRxiv that has all the apprearance of a potential major breakthrough in anti-aging research. The researchers claim they've made a mammal 54% younger with a few simple injections. The internet has been buzzing about the news ever since, with Josh Mitteldorf, who has written two books on aging, writing, "I believe major rejuvenation has been achieved in a mammal, using a relatively benign intervention that shows promise of scaling up to humans. I'm going to stake my reputation on it."
The paper describes treating old rats with injections derived from the blood plasma of young rats. As a result, the old rats showed DNA methylation clocks more typical of younger rats.
bioRxiv is a site for publishing pre-print scientific papers, that is to say, ones that have not finished the process of peer-review. The authors aim to publish the paper in a peer-reviewed journal. In its current form, the paper is missing important data and the experiment cannot be reproduced.
Methylation patterns were rolled back 75% in liver tissue, 66% in blood, 57% in heart tissue, and 19% in the hypothalamus: an average rejuvenation of 54.2% across four tissues. It is notable that not all tissues showed equal improvement on the methylation clock. In particular, the hypothalamus seemed stubborn. However, the treated rats "learned and remembered better" than the controls. Strength was up, fat was down, good cholesterol up, bad cholesterol down, and the biomarkers measured in the blood "were altered towards the values of young rats, without exception."
David Sinclair, a tenured professor at Harvard genetics department and a regular in the media, commented favourably on the paper, saying, "So are the result believable? I see nothing wrong with the epigenetic clock analyses, the stats "Horvath is the best there is. It's also hard to see how the other measures could be messed up."
So far it sounds like we should get pretty excited. Let's take a look at what the theoretical basis of the research, the empirical results, and the pathway from here to human rejuvenation. 

Methylation theory
The researcher, Harold Katcher, made his name as co-discoverer of the breast cancer gene, brca1, in 1994 and has published actively since then. He writes, "I have thousands of citations in the literature, with publications ranging from the discovery of the human 'breast cancer gene', to protein structure, bacteriology, biotechnology, bioinformatics, and biochemistry". 
Another co-author is Steve Horvath, the developer of 'Horvath's clock', a way of measuring the biological age of tissues based on which genes are active, versus which genes have methyl locks on them.
The team and their research represents a mild rebellion in the ranks of aging research. The dominant theory about biological aging  --but not the only respectable one -- is about damage. The body, in its day-to-day running, accumulates damage, much like wear on machine parts. Over time the damage builds up, causing what we know as old age.
Katcher (along with Tom Rando, Michael and Irina Conboy, and others) believe something different. Molecules in the blood give instructions to cells telling them to act young or old, and part of what it means to 'act old' is to lock down some repair mechanisms. They believe that the body has mechanisms capable of repairing the damage, but doesn't use them. 
Gene expression can be locked down by modifications called 'methylation'. For example, in response to fasting, certain genes that control appetite become methylated and switch off. According to the methylation theory of aging, our body's repair mechanisms become methylated over time, leading to the breakdown and age-related diseases.
There is some good evidence backing the methylation theory. By measuring the methylation of DNA, scientists can tell the age of a tissue sample to within 5% accuracy. Factors known to accelerate aging -such as obesity and Down's syndrome-  also accelerate DNA methylation. Katcher presented the argument in a 2013 essay called 'Studies that Shed New Light on Aging', and also in a 2015 paper 'Towards an evidence based theory of aging'.
It would be good news if the methylation theory is true. Repairing cellular damage would be hard, but if cells can be old or young depending on what signals they receive, then we need only identify the signalling molecules and inject them. The race is on. Two years ago, with funding from Akshay Sanghavi, Katcher set up a lab in Mumbai and got busy turning the methylation theory of aging into a practical therapy.

The mysterious 'Elixir'
The current study used six young rats (aged 30 weeks), and 12 old rats (aged 109 weeks), half of whom got the treatment and half of whom did not. The old rats in the treatment group were injected with something derived from the blood plasma of the young rats. What exactly? The paper is thin on details, just calling it "plasma fraction". Until Katcher and his partner Akshay Sanghavi can get a patent, they are keeping the recipe a secret. Katcher has repeatedly stated that he expects the relevant molecules can be synthesised without the need to harvest blood from young people. 
The desire to protect their discovery is understandable, but one could argue that they should have held off on publishing the experiment until their patents were secured. Reproducibility is a key part of the scientific method, and it is impossible to reproduce their study as it stands. (As a side note, the instrument used in DNA methylation profiling also falls short of reproducibility. The paper describes it as a "custom array contains two thousand probes selected from human biomarker studies" without specifying what these probes are.)
The treatment described in the paper is agreeably non-invasive: "Plasma fraction treatment consists of two series of IV injections, four times on alternate days for 8 days. A 2nd series of injections were given 95 days later. In its entirety, the experiment lasted 155 days." Katcher has said that if this becomes a human therapy, it would require a series of injections every few years.
Katcher's initial plan had been to give old rats the whole blood plasma of young rats. But in the current paper, blood plasma per se was not used, but an unknown 'something' from the plasma. The paper says "Although transfusion technologies for humans are well-developed and safe, transfusion of small animals is still at the infancy stage of development, requiring state-of-the-art techniques and remains challenging. We used a unique plasma fraction "Elixir" developed by Nugenics Research." (Nugenics is Sanghavi and Katcher's company.)
David Sinclair comments, "What is in the plasma fraction that helps? Proteins, small chemicals, exosomes?" We don't know, but Katcher's statements that the substance can be synthesised makes exosomes unlikely.

Measuring rejuvenation
Whatever it is, it seems to have worked. The paper reports, "Crucially, plasma treatment of the old rats [109 weeks] reduced the epigenetic ages of blood, liver and heart by a very large and significant margin, to levels that are comparable with the young rats [30 weeks]... According to the final version of the epigenetic clocks, the average rejuvenation across four tissues was 54.2%. In other words, the treatment more than halved the epigenetic age."
The study required a new clock to quantify the age of rats from their DNA methylation. The paper says, "To build the human-rat clock, we analyzed previously generated methylation data from n=850 human tissue samples". It seems unusual to use human tissue as a source of data for studying rat tissues. The paper does not explain why human tissue was used. What's even stranger is that the human tissue samples are from AIDS patients, from the Cape Town Adolescent Antiretroviral Cohort study, and the National NeuroAIDS Tissue Consortium which "collects and distributes well-characterized antemortem and postmortem tissue specimens with clinical and serological data from HIV-infected individuals". Why was methylation data from HIV-infected humans used to train a rat model? Did they only take data from the non-HIV-infected controls? The paper doesn't say. It is likely that using AIDS sufferers rather than healthy people could distort the DNA methylation data.
It wouldn't be that interesting if a fringe group developed a clock not generally thought to be important to aging, and then reset that clock. But that's not the only change measured in the rats. The paper also reports changes in senescence burden, biomarker levels, and behaviour.

Senescent cells
"Plasma fraction treatment reduced the level of senescent cells by a very considerable degree". David Sinclair comments, "senescent cells were reduced "by a very considerable degree". Presumably, the immune system cleared the senescent cells. This is what the field is looking for." Part of what makes this interesting is that senescent cell burden is separate from epigenetic aging; if a treatment directly addresses aging in the methylation paradigm, and somehow leads to senescent cells also being cleared up, that indicates a broad-spectrum rejuvenation. However, the quality of the data on senescent cells is low: the effect is shown by images, with the accompanying statistical analysis notably absent. It is unusual, even for a pre-print awaiting peer review, to be missing this data. Someone familiar with the technique of staining to detect senescence markers notes that there seems to be an unusual amount of blue staining in the brain tissue of the old rat, possibly indicating a methodological error. (Fig 7 of the paper, click for image) 

Outside of the group of scientists who believe that DNA methylation is key to aging, others believe that senescent cells and inflammation are to blame. Katcher's work shows promising results at addressing these problems. The paper says, "Plasma fraction treatment reduced the level of senescent cells by a very considerable degree", and Katcher has commented, "I can definitively say that chronic inflammation due to aging can be reversed with factors present in young blood". As senescent cells and inflammation markers weren't specifically removed by the intervention, it seems to work by flipping epigenetic switches, turning on the body's disposal mechanisms to clear out the trash.

Biomarker results
The paper claims that "accumulation of fat in old tissues was greatly reduced". However, no quantified measures of adipose tissue accompany this claim, as would be expected in the scientific community.
Biomarkers in the old rats "were altered towards the values of young rats, without exception". Biomarkers tested include total bilirubin, direct bilirubin, SPGT (serum  glutamic-pyruvic  transaminase), SGOT (serum glutamic-oxaloacetic transaminase), triglyceride, HDL (high-density lipoprotein), cholesterol, glucose, creatinine, BUN (blood  urea  nitrogen), total protein, IL-6 (a marker of inflammation), and oxidation markers glutathione (GSH) and superoxide dismutase (SOD). Again, the data here leaves something to be desired: it is presented as graphs without detailed numbers or statistical analysis.

Behavioural results
Performance in cognitive tests improved: "it was clear that treated rats remembered the maze much better than the untreated ones". Strength also increased. They write that "At 15 days post-treatment, the strength of plasma fraction-treated old rats was indistinguishable from that of young ones." However, it seems behaviour was not measured under conditions of blinding.

Conclusion
Regardless of what was in the plasma fraction, and regardless of whether this ever scales up to humans, the study is noteworthy for major rejuvenation in a mammal. (Tiny creatures like yeast and nematodes have been rejuvenated before.) It seems likely that the same results could be achieved by taking the blood plasma from a young animal and putting it into an old animal. Early rumours of Katcher's research suggested this. A study published in 'Nature' in 2014, and another in 2016 also lend weight to the rejuvenating powers of young blood.
It's not easy to transfuse plasma in small animals like rats. Blood loss becomes an issue. Mechanically it's easier in humans, but what about morally? The fear of Countess Bathory scenarios where the rich and old need the blood of the young and poor is at the forefront of much popular writing around this area, and dominated the Reddit comments on the research. If Katcher's team have identified and isolated molecules in young plasma that can have the same effect, that is a significant breakthrough that will shape the field in years to come.
Improved physical and cognitive performance are nice, but what would really convince the skeptics is data on how long these rats live. If treated mice lived two years longer than controls, the team will have a promising treatment on their hands. There's no way to get that data but to wait, and restrictions caused by the Covid-19 pandemic are delaying research.
Katcher and Sanghvi have not yet found a suitable partner to provide financing for human trials, and have not yet applied for patents, with Sanghvi commenting, "we plan to file patents worldwide sometime this year". Until the patents are filed, the nature of the treatment will remain a secret. Human trials may also take years to get approved and conducted. In the meantime, none of us are getting any younger.

Eternus Science

Neurohacker Collective put rigorous research into the formulation of their Qualia nootropic stack products which debuted in 2016. They now have turned their research to the riddle of aging and the decreased cellular energy that initiates many aging symptoms. The result is Eternus, a 36 ingredient formula designed to be the most comprehensive stack on the market for cell energy support, and delaying the effects of aging as long as possible.
Aging begins at the cellular level. The roughly 37 trillion cells in our bodies are performing trillions of metabolic functions each second. Decreases to the efficiency and energy of cellular function, underlies virtually all symptoms we associate with aging, from wrinkling skin and sagging muscles, to greater lethargy and brain fog, to poorer sleep and longer physical recovery times.
Comprehensive support for cell energy and efficiency lies at the bedrock of limiting the effects of the aging process, but it is an incredibly complex challenge. We all age, but the rate of aging and the negative symptoms associated with that process are highly variable. To make the rate and symptoms of aging as slow and subtle as possible, a nutritional formula must account for a broad range of cellular functions simultaneously.
These types of complex formulation requirements are where Neurohacker Collective separate themselves from most stack formulators. They specialize in formulation modeling premised on complex systems science, which incorporates dozens of ingredients dosed in precise synergistic relationships with each other, to support the body’s biochemical pathways to self regulate optimally. This approach is in contrast to a lot of pharma and nutra formulators who override those pathways to achieve an isolated benefit by externalizing side effects to other parts of the body, which can further exacerbate regulatory dysfunction.
The following is a deep dive into Eternus, which addresses cell energy and the aging process in at least 6 distinctive ways.

What is Eternus?

Eternus is a natural cell energy stack designed to comprehensively limit the negative effects of the aging process. It has been formulated by Neurohacker Collective, a San Diego-based company with a mission to create products that improve human performance by supporting our natural complex physiology rather than overriding it.

6 Ways Eternus Supports Cell Energy & Better Aging

1) Promotes a Fitter Mitochondrial Network

If your mitochondria don’t function properly, your cells will struggle to produce energy. With insufficient energy being produced, you’ll feel more tired and lethargic (R).
And poor mitochondrial health doesn’t only cause physical sluggishness.It also is linked to brain fog and neurodegenerative diseases, while improving mitochondrial function may reverse these conditions (R, R, R).
The mitochondria also initiate the production of steroid hormones, including cortisol and all sex hormones. That’s why malfunctioning mitochondria can cause hormone imbalances (R).
Another key function of the mitochondria is to commit cellular suicide – known as apoptosis – in response to excess stress, damage, or mutations. Evolutionarily, it is better for the damaged cells to commit suicide than to spread more oxidative stress, or to go on and damage other cells which can potentially develop into cancers (R).
Supporting the mitochondria and reducing oxidative stress generally protects the neurons by preventing apoptosis. In a small clinical study, a comprehensive natural approach (supplements, diet, lifestyle) sustainably reversed cognitive decline in 10 elderly patients. The program focused on reducing brain inflammation, and supporting the mitochondria and brain plasticity (R).
Eternus has a multitude of ingredients with research correlating to various aspects of improved mitochondrial health and function, including resveratrol (R), lipoic acid (R), n-acetyl-L-cysteine (R), and Coq10 (R).

2) Boosts Production of NAD+ & Optimizes NAD+: NADH Ratio

Nicotinamide adenine dinucleotide (NAD) is a coenzyme that consists of adenine and nicotinamide, and is found in all living cells.
NAD exists in two forms: NAD+ and NADH respectively. NADH contains 2 more electrons than NAD+.
Low NAD+ quickens aging. In mitochondria of young people, NADH can readily donate its electrons to generate NAD+. During the aging process, increased DNA damage reduces NAD+, leading to reduced SIRT1 activity and reduced mitochondrial function (R ).
In addition, during aging, the decline in the function of genes that control circadian rhythm can reduce NAD+ levels (R).
NAD+ also has compelling correlations to cognitive health. In a mouse model of Alzheimer’s disease, increasing NAD+ by supplementing with nicotinamide riboside restores cognitive function by increasing PGC-1alpha levels (R).
Supplementation with NAD+ intermediates, readily increases cellular and mitochondrial NAD+, and reverse many aging or disease processes associated with low NAD+ (R, R2). There is strong evidence that B vitamin levels have direct correlations to NAD+ production (R), with niacinamide (B3) in particular showing a particularly strong correlation (R). Eternus supplies a stack of B1, B2, B3, B5, B7, B9 and B12 vitamins in its formula.
While boosting NAD+ is a useful strategy, it’s also important to increase the NAD+ : NADH ratio. Increasing the cellular consumption of NADH is an additional lever toward that end. Calorie restriction induces an enzyme called Nrf2, which is considered to be a master regulator of cellular defense; it’s responsible for many cellular protection processes and involved in mitochondrial biogenesis (i.e., building new mitochondria). This enzyme then changes how other genes (and the enzymes the genes produce) express themselves, including a cellular detoxification enzyme called NQO1. In order to protect cells from potentially harmful agents, NQO1 uses NADH, resulting in lowering of cellular concentrations and an improved NAD+ : NADH ratio. Upregulating the Nrf2 → NQO1 pathway is the next piece of the puzzle. It’s part of addressing programmed aging.
A host of substances have evidence of boosting Nrf2 which are found in Eternus, such as R-Lipoic Acid (R), rosemary extract (R), french grapes extract (R?)

3) Elevates ATP Levels

Adenosine triphosphate, or ATP, is a cell’s “energy carrier” or “energy store” molecule. This is true of eukaryotic and prokaryotic cells, although the ATP production mechanism differs across the two types. ATP is the main source of energy for most cellular processes.
Low ATP levels are often found in people suffering from Chronic Fatigue Syndrome (R), and even moderate depletions of ATP have been linked to sizable increases in oxidative stress (R), while higher ATP levels have been correlated to increases in muscle mass (R) and increased capacity during high intensity activities (R).
Many ingredients in Eternus have been associated to increasing ATP levels including CoQ10 (R), and Eternus contains elevATP® specifically for that purpose, which contains a combination of trace minerals from ancient peat, including ionized magnesium and apple polyphenols, which has been correlated to increased ATP output in clinical studies (R).

4) Upregulation of Sirtuins

Sirtuins are a family of proteins critical to healthy aging. The regulate cellular health by performing critical biologic functions such as DNA expression.
When proteins are undergoing stress, acetyl groups are added to proteins as a response to changes induced by inflammation and oxidation.
Sirtuins remove these acetyl groups to keep the protein in service longer than usual, while simultaneously stabilizing the charge state of the carbon backbone in protein to resist any further changes in their shape. This allows your cellular proteins to live longer and you can save energy on other processes.
Sirtuins such as SIRT1 protects us from nitric oxide. When you have good SIRT1 levels and activity, nitric oxide will stimulate DNA repair genes (via deacetylation of FoxO1). Otherwise, nitric oxide will stimulate genes that will cause the cell to self-destruct (R).
Sirtuins play a major role in good sleep as well. SIRT1 regulates the strength (amplitude) and the duration of circadian gene expression in the retina by removing acetyl groups from key circadian clock regulators, such as BMAL1 and PER2.
In aged mice, SIRT1 levels in the SCN (circadian command center) are decreased, as are those of BMAL1 and PER2, causing a longer circadian period, a more disrupted activity pattern, and an inability to adapt to changes in the light entrainment schedule. Young mice lacking brain SIRT1 have similar effects to these aging-dependent circadian changes, whereas mice that overexpress SIRT1 in the brain are protected from the effects of aging (R).
Anything that increases NAD+, will increase SIRT1 activity. The relevant ingredients in Eternus which have already been listed to that end, but additionally, there is evidence that SIRT1 and SIRT3 activity increases from supplementation with lipoic acid,also found in Eternus, appearing to do so directly (R).

5) Activation of AMPK

AMPK(5′ AMP-activated protein kinase) is an enzyme that plays a key role in energy balance. All creatures from yeast to humans have this enzyme (R).
AMPK can detect the level of energy (number of ATP molecules) in a cell and helps regulate responses when it gets too low or high.
AMPK is produced in a number of tissues, including the liver, brain, fat cells and muscle (R).
AMPK in the hypothalamus senses our level of energy production in the body (energy in the form of ATP). It increases energy expenditure and can also increase appetite (when increased in the hypothalamus) (R).
When cellular energy is low, AMPK is activated and targets a range of processes, the net response of which is an increase in energy production and a coordinated decrease in energy (ATP) usage (R).
AMPK also inhibits the production of fatty acids, cholesterol, and triglycerides, and instead stimulates fat breakdown (R).
A multitude of ingredients in Eternus have been correlated to increasing the activation of AMPK, including Carnitine (R), gynostemma (R), CoQ10 (R), and resveratrol (R).

6) Support for Insulin Regulation

If you are insulin resistant, your brain will not get the message that insulin is trying hard to convey (that you have high levels of sugar in your bloodstream). In this way, insulin resistance promotes hunger. You eat and insulin is released, but your body tells you to eat some more despite the ability of insulin to act as a satiety hormone. Hence why obesity is linked to brain insulin resistance (R). 
When rats had their brain insulin receptors removed, they ate more, developed insulin resistance, and became obese (R). There is a correlation between insulin resistance and fat accumulation in the liver (R). Beyond a weight loss regimen and regular exercise, both of which can decrease insulin resistance, there are a number of supplement foods found in Eternus which can aid in this as well, such as magnesium (R),resveratrol (R),and lipoic acid (R).

What Makes Eternus A Unique Cell Energy and Aging Formula?

1) Comprehensive Targeting of Multiple Processes that Underlie Cell Energy & Aging

The white paper on Eternus lays out a very balanced, multi-pronged strategy in this formulation for addressing not only the 6 categories listed in this review, but also an accounting for the sub-categories and considerations comprising them. The scientists and medical professionals behind Eternus mapped out all the factors that affect cell health and aging to ensure their formulation addresses them all.

2) Synergistic Ingredients

Synergy is when a combination of ingredients produce an effect greater than the sum of its parts. Many ingredients in Eternus have more than a single positive effect and when you stack them together, some effects become stronger than when they are taken separately.

Eternus Ingredients

The Eternus formulation transparently lists all 38 ingredients comprising it and the dosing of each is consistent with the amounts the benefits that warrant their inclusion.

Positive Subjective Effects From Eternus

You can notice very significant improvements from Eternus within just a few days, such as:
- Noticeable increases in energy and vitality.
- Decreases in brain fog and more sustainable mental energy.
- Quicker recovery times from workouts and activities.
- Decreased pain and discomfort from decreased inflammation.
- Improved sleeping quality and easier transitions to wakefulness.

Bad Side Effects

Common negative side effects include:
- Possible upset stomach if Eternus is not taken with food.
- Potential restlessness if Eternus is taken late in the day.

Who is Eternus For?

Eternus is for anyone looking to maximize nutritional support for cell health and cell energy, particularly for those who are looking to delay the onset of age related decline as significantly and comprehensively as can be done through premium nutrition.The product comes with a 100-Day money back guarantee, and significant subjective improvements to vitality and energy are felt by most within the first week, providing quick evidence that cellular energy and efficiency is improving.

Buy Eternus

You can try Eternus by clicking here. Choosing the subscription option (which you can cancel anytime) gets you 50% off the first month supply, and using coupon code LONGECITY gets you an additional 15% off your first purchase.
A comprehensive cell energy product like Eternus can be a tremendous compliment to the foundations of good diet, exercise, and sleep, in holding back the hands of time for as long as possible, and sustaining a high physical and mental quality of life for decades to come.