LONGECITY

Interesting tech talk by Gregory Benford here

He claims to have data on drugs made of GRAS substances which will increase longevity by 30% (atleast in fruit flies) and which should be out in the market in a year.
He's apparently been taking the top drug for atleast a year himself and looks quite spry.

Other interesting tidbits:

• Caffeine more than 10 cups a day is bad for you
• Chocolate is good
• There are a lot more negative consequences to supplements than realized (through bad combinations or bad dosages)
• He's very much pro statins (generally recommended after age 40)

What do you folks think?


PS: First post although I've been lurking for quite a while

What kind of "Chocolate" is he referring to does he mean cocoa? I've seen the talk very interesting, I'd love to work in genomics and bioinformatics.
Edited by CerebralCortex, 27 November 2009 - 03:17 PM.

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What kind of "Chocolate" is he referring to does he mean cocoa? I've seen the talk very interesting, I'd love to work in genomics and bioinformatics.

He mentions theobromine specifically, which is why it was interesting since it's thought to be similar to caffeine which he's against.

very credible. one of the more thoughtful discussions ive seen in the last year.

nice to see he is against the mass-pill taking exhibited by people like Ray Kurzweil. i look at people like Kurzweil and our late friend TFI (who was downing 30+ diff supplements, smoking, and then was incarcerated), and wonder.

also parallels with our human needs to have a well balanced diet/set of nutrients to function properly. that one single nutrient like resveratrol will not be the answer to longevity but is probably part of the "puzzle" of nutrigenomics that one could see useful in a broader supplement package.

id really like to know what his lead compound is, but i guess we will all know within a year
Edited by prophets, 27 November 2009 - 04:03 PM.

Very interesting talk. Some comments from Reason over at FightAging (Genescient Envisioned as Sirtris++). I think Genescient has a very nice approach. They have evaluated the genomic networks in George Rose's Methuselah flies compared to ordinary flies, and then sought compounds or mixtures of compounds from the GRAS subset that would move the genomic networks of ordinary flies (or maybe it was the corresponding human networks...) in the more long-lived direction. The plan is to sell this as a supplement. It would of course be interesting to know what's in it. It will be interesting to see how they market it when they can't make health claims. Of course, since aging isn't defined as a "disease", is it really a health claim if they say this stuff will make you live longer? I dunno. It'll be interesting, that's all I can say. I wonder if they will disclose the contents, or if someone in the underground will have to analyze it? I suspect one or the other will happen, particularly if they get impressive mouse results with it. That will really be the first acid test. Or better yet, some species a bit more like humans. They are leaning pretty heavily on the concept the fruit flies are tiny humans with wings, but they do make a hell of a laboratory for genetic selection work.

idk how they will make any money off of commonly available nutrients that anyone can just knock off themselves and mass produce. i bet GSK is sort of kicking themselves for drinking the kool-aid and buying Sirtris for such a bold price tag.



if anyone can figure what their "most important" compound is related to dna repair for the genescient product, i'd be curious.

Not sure about statins given the rather dubious research surrounding them, especially when the real solution is proper lifestyle management. In fact, I would be hesitant to endorse anything showing only 30% extension in fruit flies and with no trials in larger organisms. Figuring that these animals have much faster (shorter) lifespans, 30% isn't too much life extension and will probably (if it doesn't end up proving to be deleterious) translate into significantly lower numbers when applied to humans.

That said I share his opinion about supplements. Often times these substances exist in precarious harmony with other dietary derived nutrients. Supplementing huge amounts of just a few specific nutrients might inadvertantly unbalance the entire arrangement and cause more harm than good. Plus there are issues with contamination for many people that forgo proper supplier research. I think it would be instructive to realize that most supplements won't induce meaningful lifespan increase, but will (at best) only increase health span.

At any rate, I'm all for people doing more research on life extension. Hopefully in the next 30 years we start seeing some truely promising life extension treatments come to market in safe and well researched forms.

Not sure about statins given the rather dubious research surrounding them...

I consider anyone who suggests statins are good for everyone to be suspect at the very least.
Edited by rwac, 28 November 2009 - 08:03 AM.

In fact, I would be hesitant to endorse anything showing only 30% extension in fruit flies and with no trials in larger organisms. Figuring that these animals have much faster (shorter) lifespans, 30% isn't too much life extension and will probably (if it doesn't end up proving to be deleterious) translate into significantly lower numbers when applied to humans.

you misunderstood what the guy said. he said the methuselah files live MULTIPLES longer than control flies, and that they expect the similar longevity pathways to induce a 30% benefit in humans.

In fact, I would be hesitant to endorse anything showing only 30% extension in fruit flies and with no trials in larger organisms. Figuring that these animals have much faster (shorter) lifespans, 30% isn't too much life extension and will probably (if it doesn't end up proving to be deleterious) translate into significantly lower numbers when applied to humans.

you misunderstood what the guy said. he said the methuselah files live MULTIPLES longer than control flies, and that they expect the similar longevity pathways to induce a 30% benefit in humans.

Actually you misunderstood what he said. Methuselah flies live multiple times longer than the control flies. However, the pharmacological analogues for the longevity genes only induce a 20-30% lifespan increase in those same control flies. These are the very same compounds he plans to sell next year. What does this mean for humans? Probably not much.

"and you can tell when they are going to die because they can no longer do the mating dance"

thanks for posting!

One possible observation with the longevity or should I say "short"ivity genes is that can can switch the individual to an altruistic mode of self sacrifice and that is why I think they are conserved across the phylogenetic tree. It's like having a computer network where a machine will shut it self down if it becomes an infected host. In real terms of human life a cytokine storm arises when an individual catches a viral infection that could destroy the individuals entire community if it were to spread. Instead the individuals own immune system attacks and destroys the individual from within. Therefor the individual will altruistically destroy itself instead of spreading the pandemic further throughout the community. This response is conserved in everything from yeast to humans. Other diseases such Diabetes, atherosclerosis, Alzheimers, dementia and strokes are the naturally initiated shutdown sequence when a person in the community carries so many biological pathogens they become an infectious danger to those around them.

Now having said all this I will watch his talk

I think the biggest concerns I have with models of increasing life span is that we are not increasing healthy lifespan. If we are keeping millions of 90 years olds alive on warfarin that should have died of a stroke 15-20 years ago I don't consider it a victory for increased healthy lifespan. It is a major sign that we are tempting fate and risking the destruction of our community/ civilization/ species. If yeast are smart enough not to keep the old yeast alive then why do we try to?

Increasing lifespan through drosophila type experiments doesn't help if it simply removes these "disease causing genes" it should actually improve the immune system so much that the disease causing genes won't need to be activated. Natural selection selects AGAINST communities that completely lack disease causing genes.
Edited by caston, 28 November 2009 - 12:14 PM.

I think the biggest concerns I have with models of increasing life span is that we are not increasing healthy lifespan. If we are keeping millions of 90 years olds alive on warfarin that should have died of a stroke 15-20 years ago I don't consider it a victory for increased healthy lifespan. It is a major sign that we are tempting fate and risking the destruction of our community/ civilization/ species. If yeast are smart enough not to keep the old yeast alive then why do we try to?

He talks specifically about extending healthspan, not just lifespan. You're making the Tithonus Error.

He talks specifically about extending healthspan, not just lifespan. You're making the Tithonus Error.

/confirmed. he argues against CR (and taking your metabolic rate down). he argues in favor of a "vigorous" and robust extension of life.

again, if anyone can pick up on what the "one critical DNA repair mechanism" is that he highlights as important to life extension, i think it'd be really nice to know. not sure if it is telomerase or maybe something like selenium, but it seemed critical.

Ok, I take my knee-jerk response back.
It's a very interesting video.

I still think most of my points are valid. Sure the tribe with a few elders probably has an advantage over the tribe with no elders but the tribe with to many elders has a severe disadvantage compared to both the other tribes. I don't think this approach is the going to increase healthy lifespan. It may reduce the symptoms of disease and increase lifespan creating some good selling drugs but this isn't going to be a good thing for us in the long term and we could see this if we had a much better understand of what is going on in the bacterial world and microbiome of each individual.

It may look like an increase in healthy lifespan but the diseases of aging are just as much about the host response to biological pathogens as they are the pathogens themselves, and it won't prevent proliferation of the biological pathogens that attack the organism at every level where normally the host response is to engage in the aging and disease program to shut itself down.

Perhaps you are arguing that some aspects of extreme accuracy in DNA repair and protein folding, chromatin restoration and such processes are given less than the highest priority to conserve resources and or allow some evolutionary changes?
Edited by caston, 29 November 2009 - 03:24 PM.

I still think most of my points are valid. Sure the tribe with a few elders probably has an advantage over the tribe with no elders but the tribe with to many elders has a severe disadvantage compared to both the other tribes. I don't think this approach is the going to increase healthy lifespan. It may reduce the symptoms of disease and increase lifespan creating some good selling drugs but this isn't going to be a good thing for us in the long term and we could see this if we had a much better understand of what is going on in the bacterial world and microbiome of each individual.

It may look like an increase in healthy lifespan but the diseases of aging are just as much about the host response to biological pathogens as they are the pathogens themselves, and it won't prevent proliferation of the biological pathogens that attack the organism at every level where normally the host response is to engage in the aging and disease program to shut itself down.

You should watch the video. They increased the lifespan of flies and looked at their genetic activity.
These particular flies were more vigorous in every way, as well as having a longer lifespan.

These particular flies were more vigorous in every way, as well as having a longer lifespan.

Do they have less pathogenic bacteria in their microbiome?

Do they have less pathogenic bacteria in their microbiome?

This is a very good point. I would guess not.

I just saw Gregory Benford talk at The Singularity Summit Australia 2010. Interesting talk with nothing really new (actually less comprehensive than above talk), he is a very funny guy, however he did mention that his company Genescient has a product StemCell 100 out in three weeks, and alluded that he is already taking the supplement. Problem is he did not elaborate AT ALL on what it does, how it works, or any testing that has been done on the compound, just a rather vague "$1/day for 116% lifespan". He did also mention that it was "completely new" and would be available for purchase over the Internet shortly.

Thoughts?
Edited by e Volution, 14 September 2010 - 11:45 PM.

I just saw Gregory Benford talk at The Singularity Summit Australia 2010. Interesting talk with nothing really new (actually less comprehensive than above talk), he is a very funny guy, however he did mention that his company Genescient has a product StemCell 100 out in three weeks, and alluded that he is already taking the supplement. Problem is he did not elaborate AT ALL on what it does, how it works, or any testing that has been done on the compound, just a rather vague "$1/day for 116% lifespan". He did also mention that it was "completely new" and would be available for purchase over the Internet shortly.

Thoughts?

The price is right... If it does anything.

I guess we'll know more in 3 weeks. They have to disclose ingredients if they're going to sell it, though there are ways to fudge that. Well, that's what analytical labs are for, right?

Just did a google search on stemcell 100 and got these two sites:
http://www.stemcell100.com/
http://www.lifecode100.com/

The first has nothing, but the page title is "Life Code" and the second has details of a product called Stem Cell 100™. It seems to be resveratrol, astragalus and a couple of other compounds.

Just did a google search on stemcell 100 and got these two sites:
http://www.stemcell100.com/
http://www.lifecode100.com/

The first has nothing, but the page title is "Life Code" and the second has details of a product called Stem Cell 100™. It seems to be resveratrol, astragalus and a couple of other compounds.

Active Ingredients: There are four components that make up the patent-pending combination in Stem Cell 100TM. The first ingredient is an natural amino acid [(2S*,3R*)-2-amino-3-hydroxybutanoic acid] that is present in high concentration in sperm cells and is required for embryonic stem cell growth and pleurapotency. Three of the active components are highly extracted natural herbs that are standardized for high concentrations of active components that promote adult stem cells: Targetes erecta standardized for ß,e-carotene-3,3'-dio; Pterocarpus marsupium standardized for a Long Half Life (LHL) resveratrol analog named LHL-resveratrolTM; and Astragalus membranaceus.

Stem Cell 100TM
Adult stem cell function declines with age leading to the decline in fitness

The potential therapeutic use of stem cells is a very hot topic these days. Most of the attention has focused on embryonic stem cells and induced Pluripotent Stem cells (iPS cells), which can form every tissue type in the body to regenerate failing organs. The problem is that detailed knowledge is lacking for how to stimulate the embryonic stem cells to form differentiated tissues (e.g. cells that form the heart, pancreas, muscle, and brain). Moreover, because embryonic stem cells are unlimited in their ability to form any type of tissue, the risk of cancer looms large over the therapeutic use of embryonic stem cells. For example, both embryonic and IPS stem cells can form tumors called teratomas when injected into immune-compromised mice. Enter the body's adult stem cells, which have not generally been associated with cancer and have been used safely as therapeutics in many countries. The problem with adult stem cells is that it is difficult to get enough of them to be effective for most indications or target the harvested adult stem cells to the proper tissue. Moreover, there are scores of different types of adult stem cells in the body, so picking the best type of adult stem cell for a particular therapeutic can be challenging. Thus, adult stem cell therapeutics with all its potential to regenerate damaged organs and tissues is still a work in progress.

But what about the many populations of endogenous adult stem cells that everyone has embedded in every organ system of the body? All the organs and differing tissues of the body appear to have adult stem cells available for regenerating cells in case of injury or disease. It was recently discovered that even brain neurons and heart muscle cells (previously thought to be non-dividing and irreplaceable in adults) have their own reservoirs of adult stem cells for regeneration. Unfortunately, as we age most adult stem cell populations either decline in number and/or lose the ability to differentiate into functional tissue-specific cells. For example, cardiac muscle stem cells exist but old folks have only one half the number of cardiac stem cells found in young people. Thus, adult stem cells become more and more dysfunction with age, which progressively increases organ and tissue dysfunction with age.

There are many examples revealing the role of adult stem cells in aging. First, the outer surface of your skin continuously sloughs off dead cells, so that adult stem cells must continuously replenish the dying skin cells to maintain the skin as an effective protective barrier to the outside world. With age, there are progressively fewer functional skin stem cells, so cell turnover in the skin slows, leading to thinner, dryer skin that loses its elasticity and youthful beauty. Second, hair also thins and goes grey, as functional follicle stem cell decline and the adult stem cells generating hair color also decline. Third, the differing adult stem cells that maintain the tissues composing skeletal muscle, pancreas, heart, bone, liver, kidney, and the immune system lose functional capacity, raising the potential for decline in tissue function or outright failure with age. As a final example, the five senses of sight, hearing, smell, taste, and touch slowly wane with age, as the declining stem cell populations responsible for maintaining these functions are unable to fully replenish the sensory neurons after injury and random cell death.
Stimulation of endogenous adult stem cells can increase health and fitness

If your own adult stem cells are a key factor in aging and disease, then one novel way to slow aging and disease is to stimulate your own adult stem cells to maintain their proper numbers and functional capacity to differentiate into the various tissues as needed for repair and regeneration. This makes sense, because in most, if not all, organs of the body, old cells are continually being replaced by new cells coming from the adult stem cell populations. If stem cells are not producing enough new cells, then organs slowly decline in function as you age. Thus, stimulating your own stem cells can be a winning strategy to stave off many of the disorders associated with aging.

In practice, however, stimulating adult stem cell populations in the body is not a simple task. If the proliferation of adult stem cells is over stimulated, then one may get overgrowth of tissues or a potential tumor. Alternatively, one may stimulate the stem cells to proliferate in a balanced and regulated way, but the stem cells lose functionality and cannot differentiate into the desired specialized tissues to replace senescent cells. These twin problems - promoting over stimulation or dysfunctional stem cells - put real limits on any proposed therapeutic for stimulating stem cells. For example, most current treatments to stimulate immunity or stem cells (naïve T cells) rely on complex carbohydrates from mushrooms or microorganisms to provide antigenic material that can stimulate immunity. This will activate the immune system stem cells to make more differentiated non-stem memory T cells directed against the antigenic material, but it does nothing to stimulate more immune stem cells (naïve T cells). Indeed, chronic use of such stem cell 'enhancers' may actually lead to stem cell depletion, as more adult stem cells are exhausted from the requirement to respond to the constant presence of the polysaccharide antigen. Indeed, one theory of how the HIV virus causes a defective immune system is that it exhausts the supply of naïve T cells by the repeated attacks of the mutating HIV virus.

Stem Cell 100TM does not stimulate stem cells to differentiate or divide; it just promotes the stability and vitality of adult stem cells so they have the capacity to divide when the body signals a need for more stem cells and differentiated cells. When an organ or tissue is damaged, it will send out natural signals that new cells are needed to replace old or damaged cells. Stem Cell 100TM allows the adult stem cells to respond to the damage signal by provided new differentiated cells to replace the old damaged cells and also make more adult stem cells to keep up the stem cell population. Two other compounds in Stem Cell 100TM provide further natural support for stem cells.
Stem Cell 100TM as a Patent-Pending Life Code Product

Serving Size: One vegetarian capsule

Serving Directions: Two VcapsTM per day are preferred with one taken after breakfast or lunch and one taken after dinner. If you weigh less than 130 pounds, or want to get the most of the treatment benefit at lower cost, one may take one capsule per day after lunch.

Active Ingredients: There are four components that make up the patent-pending combination in Stem Cell 100TM. The first ingredient is an natural amino acid [(2S*,3R*)-2-amino-3-hydroxybutanoic acid] that is present in high concentration in sperm cells and is required for embryonic stem cell growth and pleurapotency. Three of the active components are highly extracted natural herbs that are standardized for high concentrations of active components that promote adult stem cells: Targetes erecta standardized for ß,e-carotene-3,3'-dio; Pterocarpus marsupium standardized for a Long Half Life (LHL) resveratrol analog named LHL-resveratrolTM; and Astragalus membranaceus.

Warnings: Stem Cell 100TM may lower glucose and/or blood pressure in some individuals. Pregnant, lactating, hypoglycemic or diabetic individuals should consult their physician before use.

Safety: The four substances in Stem Cell 100TM are pharmaceutical grade and have been individually tested in both animals and humans without significant safety issues. Those with pre-existing conditions of diabetes or hypertension should coordinate this product with your doctor, as lower blood glucose or reduced blood pressure can result from taking the normal dose of this product. Because Stem Cell 100TM is a potent formulation, do not take more than two capsules per day. If low-blood sugar headaches appear (which is possible if you have a tendency to hypoglycemia), cut down the dose to one capsule per day and eat some food every hour, or discontinue product use altogether.
Biomarkers for testing your health and fitness

It is very important to know if particular lifestyle change, exercise regiment, or supplement is really promoting longevity and fitness. Since aging is controlled by both environment and complex genetic traits, there is no single biomarker of aging that gives an objective measure of whether a behavioral or treatment change is really helpful or not. However, much research has suggested a basket of biomarkers that does estimate your current and future risk of morbidity (disease) and mortality (death). Below is listed our favored biomarkers of aging that can be used to track changes.
The Following biomarkers will be used to track changes:

* Blood Pressure and Pulse Rate
* Time to walk a mile (see www.brianmac.co.uk/rockport.htm)
* Maximum number of pushups in 2 minutes
* Reaction Time: (www.bbc.co.uk/science/humanbody/sleep/sheep/reaction_version5.swf)
* Fat Stores: Weight, BMI, waist circumference, and standing balance test
* Lipids: TC, LDL, HDL, triglycerides
* Metabolic: Fasting glucose, hemoglobin A1c, Thyroid Stimulating Hormone
* Liver & Kidney: ALT, AST, alkaline phosphatase, BUN, creatine, micro-albumin
* Inflammation: High-sensitivity C-Reactive Protein (hsCRP)

What are the expected benefits of taking Stem Cell 100TM:

(Note that not everyone will experience the same effects, as conditions vary among individuals. The general expectation is that for most health measurements that are in the Normal Range for your age, Stem Cell 100TM will promote readings that you had when some 20 years younger.)

1. Helps maintain most populations of adult stem cells to reduce age-related losses
2. Helps maintain the vigor and health of the cardiovascular system
3. Helps maintain healthy blood glucose levels that are already in the Normal Range
4. Helps maintain healthy blood pressure that are already in the Normal Range
5. Helps maintain healthy pulse rate that are already in the Normal Range
6. Helps maintain healthy cholesterol levels that are already in the Normal Range
7. Enhances skin elasticity and tightness to reduce wrinkles
8. Promotes brain and neural health
9. Promotes strength and endurance in vigorous exercise
10. Promotes a healthy immune system and joint health
11. Promotes healthy kidneys, liver, and pancreas
12. Enhances sexual potency and performance
13. Promotes improvements in eyesight and age-related focus on nearby objects
14. Promotes healthy intestines, colon, and bowel regularity

I forgot one very interesting and important part of his talk: An audience member asked if he planned on making some of the data he gleaned from DNA analysis of the long-lived fruit flies, and he said that is a question he is wrestling with very much right now, and in fact was heading back on a plane to the states that very night to rush to a Genescient board meeting to discuss the topic. He said he obviously has competing incentives, as the head of the company he wants to make money and maximise profits, but even more so he doesn't want to die and that is the whole reason for the company in the first place and putting the data out there will certainly help advance this goal. He also mentioned he is against the patenting of genes, instead he favours patenting of the methods of altering them, compounds, amounts, etc.

Active Ingredients: There are four components that make up the patent-pending combination in Stem Cell 100TM. The first ingredient is an [sic] natural amino acid [(2S*,3R*)-2-amino-3-hydroxybutanoic acid] that is present in high concentration in sperm cells and is required for embryonic stem cell growth and pleurapotency [sic]. Three of the active components are highly extracted natural herbs that are standardized for high concentrations of active components that promote adult stem cells: Targetes [sic] erecta standardized for ß,e-carotene-3,3'-dio [sic]; Pterocarpus marsupium standardized for a Long Half Life (LHL) resveratrol analog named LHL-resveratrolTM; and Astragalus membranaceus.

Warnings: Stem Cell 100TM may lower glucose and/or blood pressure in some individuals.

do not take more than two capsules per day.

[(2S*,3R*)-2-amino-3-hydroxybutanoic acid] = D Threonine, if I understand their notation.
Tagetes erecta is Marigold, a source of carotenes such as Lutein. In fact, beta, epsilon-carotene-3,3'-diol is Lutein.
Pterocarpus marsupium is high in Pterostilbene, a resveratrol analog. That's probably the LHL-resveratrolTM.
Astragalus membranaceus is an herb many of us are familiar with; no telling what they've standardized on.

They are forcing me to be schoolmarm-ish and mark their misspellings and grammatical errors with '[sic]'. It worries me when scientific/technical people can't get stuff like that right. It makes me wonder what else they were half-assed about.

What were they selling this for, a dollar a day? Or was it a dollar a pill? If the former, and if the formulation is decent and the quality is good, that's a good deal. You might approximate this, with some guesswork about the astragalus, though I don't know a reliable source for D-Threonine, if I have that ID'd correctly. I have no idea what it would be doing, either. Three of these compounds are things we've discussed here, but not the D-Thr.

They are forcing me to be schoolmarm-ish and mark their misspellings and grammatical errors with '[sic]'. It worries me when scientific/technical people can't get stuff like that right. It makes me wonder what else they were half-assed about.

Yeh I mean we are on the cutting-edge here at ImmInst but I would consider this a marketing fail

This might be a lead on what is standardized in Astragalus for telomerase activation:

http://www.ncbi.nlm....1&dopt=Abstract

Astragalus is used for TA-65, wonder what concentrations for Stemcell 100. It'd be nice to see a comparison since TA-65 is $200-$800 per month depending on dosage.

So... anynews on that supplement? Seems like no updates to the site, no reply to mails. Noone i asked who is in contact with folks involved got an answer. Huh.

What do you guys think would be the appropriate dosage for a cat? Any ethical issues with trying this stuff out on my pets for a while?