Does Medicine for Aging Exist?
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Published at Impact Aging you'll find descriptions of the presentations given at the Second International Conference on the Genetics of Aging and Longevity, held in Moscow recently. It's a good representative sample if you'd like to know what the mainstream of aging and longevity science looks like. What I wanted to draw your attention to was this presentation and question:

Vladimir Anisimov (N.N. Petrov Research Institute of Oncology, Russia) in his presentation "Do we really have a medicine against aging?" showed results of experiments on effects of antidiabetic biguanides and rapamycin on biomarkers of aging, life span, spontaneous and chemically-induced carcinogenesis in outbred, inbred and transgenic HER-2/neu mice and in rats.

The mTOR inhibitor rapamycin prevents age-related weight gain, decreases rate of aging, increases life span and decreases carcinogenesis in transgenic HER-2/neu cancer-prone mice. Rapamycin dramatically delayed tumors onset, decreased a number of tumors per animal and tumor size. Lifelong administration of rapamycin extends lifespan in female 129/Sv mice characterized by normal mean lifespan of 2 years. Importantly, rapamycin was administrated intermittently (every other 2 weeks) starting from the age of 2 months. Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors) and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in control group.

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Treatment of female outbred SHR mice with metformin started at the age of 3 months increased mean life span by 14% and maximum life span by 1 month. Same treatment started at the age of 9 months insignificantly increased mean life span by 6%, whereas treatment started at the age of 15 months failed to increase life span. When started at the age of 3 and 9 months, metformin delayed time of the first tumor detection by 22% and 25%, correspondingly.

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These results suggest that both metformin and rapamycin may be useful in prevention of cancer and extension of lifespan when used in rational and appropriate ages, doses and schedules.

Asking and attempting to answer questions like "does medicine for aging exist" is going to make you unpopular in some quarters no matter how you answer. The large and energetic "anti-aging" marketplace, eternally plagued by the dishonesty of its bad apples, has been crying "yes, yes, get your treatments for aging here" for about as long as mankind has existed. The invention of fraud no doubt followed the discovery of the concepts of value and trade by only a few heartbeats. When no-one could in fact do much of anything about aging, one might say "so what?" Fraud and lies about extending life were no different then than fraud and lies about anything else that didn't exist and couldn't be made to exist - such as the ownership rights to certain bridges, for example.

In these later days of science and reason, however, in which we stand upon the verge of building real and meaningful ways to treat aging, that commercial "anti-aging" market is a millstone around the necks of the scientific community. It is in fact a large part of the reason why up until very recently the aging research field was extremely hostile towards anyone talking seriously about treating aging.

So you are going to see care taken when people in the scientific community speak on such topics. For my part, I think it's completely fair to put forward that, by modern standards of drug development, you could point to rapamycin and metformin and say "these are candidate treatments for aging." By this I mean that they are likely to produce minimal benefits, have potentially ugly side-effects, and are not yet really tested for that specific usage in humans - which describes both a fair chunk of the drug discovery pipeline and many drugs out there in widespread use. We are willing to call those therapies for the conditions they are used to treat.

But let's be clear: as prospective therapies for aging, these drugs are terrible. Truly bad. They are far worse than exercise or calorie restriction - they produce lesser benefits and you get unpleasant side-effects into the bargain. So given all of that I don't think it is unreasonable to say that yes, treatments for aging exist at the present time, and they are awful.

(It is worth pointing out that a gain in life span of 20% in mice is not all that in the grand scheme of things. Exercise can do better, and calorie restriction does twice as well. Further, it is not seriously expected that any gain of 20% in life span in mice through metabolic alteration will translate to a similarly meaningful gain in human life span - which has to do with many of the differences that cause us to be long-lived already for our size. For example, calorie restriction is not thought to be capable of producing more than a few years of gain in maximal human life span, even while it produces large gains in health and resistance to age-related disease).

The real path to the future, to my eyes, is to skip over all of this longevity-enhancing drug discovery nonsense, interesting though it may be, and focus on repair of specific forms of cellular and molecular damage - such as the detailed methodologies proposed in the SENS vision. If SENS or similar programs for research and development fail to become a dominant approach to longevity science, and the foreseeable future thus remains a heaping helping of more longevity-enhancing drug discovery nonsense, then therapies for aging will continue to be generally awful.

I consider it to be unfortunate that the bulk of the pro-longevity aging research camp is focused on an inefficient path forward that will in the end lead to lesser benefits. It is their belief that this is the only practical way ahead: a laborious slog towards complete understanding of aging and metabolism, followed by an even more complex navigation through re-engineering that metabolism to age more slowly. The sheer scale and difficulty of that task is why many scientists feel that meaningful engineered longevity - more healthy years through science - is a long way away indeed.

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It is likely to be easier and less costly to produce rejuvenation therapies than to produce a reliable and significant slowing of aging. A rejuvenation therapy doesn't require a whole new metabolism to be engineered, tested, and understood - it requires that we revert clearly identified changes to return to a metabolic model that we know works, as it's used by a few billion young people already. Those rejuvenation therapies will be far more effective than slowing aging in terms of additional years gained, since you can keep coming back to use them again and again. They will also help the aged, who are not helped at all by a therapy that merely slows aging.

Comments

How about you stop constantly bashing the only sources of funding for these initiatives? I mean seriously, you hate the government, which is realistically the biggest source of research funding for these endeavours, if certain people could be convinced of their necessity. And now you're attacking the private sector too! Come on, 'Reason', be reasonable.

Posted by: Leon at June 1, 2012 12:53 AM

Leon,

One need not make in principle attacks on the private sector in order to single out for attack private organisations and individuals who happen to be con artists.

Similarly, one need not not object in principle to government funding when taking a strong stance against the funding apparatus of the FDA.

Lastly, one need not do either of these things to recognize that the priorities for allocation of funds are, across the board, wrong headed, due to the fact that they single out research streams that will be of little benefit compared to other much more promising avenues.

Reason's objections are reasonable precisely because they recognize the failings occurring everywhere, rather than imagining that those failings are the result of one particular ideological bent or another. EVERYONE is getting this issue wrong, so we may as well say so. That may seem uncharitable and uninspiring, but then so is our situation.

Posted by: Ben at June 4, 2012 5:17 AM

What are the bad side effects of Metformin? I have been taking it for quite a while and find no noticable SE, and my fasting glucose has dropped, but intermittent fasting, while easy, did nothing for that. Rapmycin I know about and don't want to take. But your objection to Metformin seems odd.

Life Extension Foundation is pretty big on Metformin. What do you know that they don't?

Posted by: Lynn Johnson at November 13, 2012 4:57 PM
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