September 29, 2009

Near Term Prospects for Increased Longevity

NY Times: “In five or six or seven years,” said Christoph Westphal, Sirtris co-founder [Sirtis was bought by GlaxoSmithKline for $720 million], “there will be drugs that prolong longevity.” [H/T Michael Annisimov, Accelerating Future]

SRT-501, the company’s special formulation of resveratrol, is being tested against two cancers, multiple myeloma and colon cancer that has spread to the liver. A chemical mimic of resveratrol, known as SRT-2104, is in a Phase 2 trial for Type 2 diabetes, and in a Phase 1 trial in elderly patients. (Phase 1 trials test for safety, Phase 2 for efficacy.)

Dr. Gallagher said that unpublished tests in mice showed that another chemical mimic, SRT-1720, increased both health and lifespan; after two years, twice as many mice taking the drug were alive compared with the undosed animals. Resveratrol itself has not been shown to increase lifespan in normal mice, although it does so in obese mice, laboratory roundworms and flies.

Sirtris has so far been doubly fortunate. No severe side effects have yet emerged from the clinical trials. The company has also been lucky in having apparently picked the right horse, or at least a good one, in a fast-developing field.

Sirtuins may not be the most important genes for longevity, Dr. Sinclair conceded at the conference, because the pathways controlled by the sirtuins, TOR and the others “all talk to each other, often by feedback loops.”

Many theories of aging attribute senescence to the inexorable buildup of mutations in a person’s DNA. Dr. Sinclair said that in his view “aging can be reversed” because the DNA mutations did not directly cause aging.

SRT1720 effect on mice

Mice without SRT1720 ran for roughly half a mile. Mice given 100 mg ran roughly seven-tenths of a mile. And mice on 500 mg of SRT1720 were able to run a full mile, twice the distance of untreated mice.

Here is an earlier article about Rapamycin being able to extend the lifespan of elderly mice by 9-13%. Rapamycin has known toxicities, such as fungal infections and pneumonia, the drug should not be taken by the general population as a kind of universal fountain of youth. So they need to find an equivalent to Rapamycin's positive effects and have them work in humans and not have the downsides.

SENS research and website

SENS is an acronym for "Strategies for Engineered Negligible Senescence". It is best defined as an integrated set of medical techniques designed to restore youthful molecular and cellular structure to aged tissues and organs. Essentially, this involves the application of regenerative medicine to the problem of age-related ill-health. However, regenerative medicine is usually thought of as encompassing a few specific technologies such as stem cell therapy and tissue engineering, whereas SENS incorporates a variety of other techniques to remove or obviate the accumulating damage of aging.

Currently, SENS comprises seven major types of therapy addressing seven major categories of aging damage, and you will find details of these therapies throughout this section of the website.

SENS Timeline and milestones

This is the first major SENS milestone, and I believe it will be achieved with laboratory mice. The degree of control that I consider sufficient is the ability to take a cohort of mice of a strain whose normal life expectancy is three years, do nothing to them until they are two years old, and get them to live an average of three more years, i.e., triple their remaining life expectancy. I often call this "Robust Mouse Rejuvenation," or RMR. My estimate for the time until this milestone is reached, if there is adequate funding, is ten years from now; almost certainly not as soon as seven years, but very likely to be less than 20 years. If funding is sluggish this could be doubled.

The second major SENS milestone, and it can reasonably be defined as the arrival of therapies that confer a postponement and repair of human aging proportional to that described for mice in milestone 1, i.e., a tripling of our remaining life expectancy with therapies initiated on our late fifties or so. Inevitably I call this "Robust Human Rejuvenation" or RHR.

My estimate for the time until this milestone is reached, starting from the time that the mouse target is achieved, is 15 years; almost certainly not as soon as five years, and could be as many as 100 years. Note that this time I make no caveats about funding, because I think it is inconceivable that shortage of funds will be allowed to slow down this work once milestone 1 is achieved.

When we reach milestone 2, those with access to the relevant therapies will have an absolutely non-increasing risk of death per unit time — they will not age. This is because we will be identifying, characterising and solving aspects of aging that appear at progressively later ages, faster than they progress to a life-threatening state. We have no idea at present what we will need to do to keep 200-year-olds hale and hearty, but that's OK, because we won't need that information for at least another 100 years. If we just pay attention to things that begin to appear in 180-year-olds as soon as we have any, as well as in 80-year-old chimpanzees as soon as we have them, and given the amount of effort we'll be putting in, our chances of perpetually keeping one step ahead of the problem are very good.
At present, the risk of death per unit time that Westerners experience in their early teens is such that if it were maintained indefinitely we would live to around 1000 years on average. (This calculation has been done many times with different data and some people get 700, some 1200; 1000 is a fair consensus.)

So 9-13% improvement in the lifespan of elderly with a procedure that has side effects has been achieved in the lab. The first SENS goal is 300% improvement in the lifespan of elderly mice. There has been 0.1 to 0.2 years of improvement in lifespace enhancement in humans for decades because of the improved treatment of various diseases and general improvements in health. Individuals can choose a healthy lifestyle (exercise, proper diet, do not smoke) and have a good chance to increase their lifespan by ten years over not following a good lifestyle.

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