Arguing for Rapamycin to Slow Aging

There is presently some debate over whether or not rapamycin actually slows aging - based on rigorous studies some researchers say yes, say no, it extends life in mice but only by reducing cancer risk. Rapamycin and various derivatives under development are presently the longevity enhancing drug candidates best supported by the evidence in laboratory mice, so there is probably a lesson to be learned here in regards to the soundness of the whole strategy of trying to slow aging via metabolic manipulation.

The researcher quoted here is a vocal proponent of one of the programmed theories of aging (the hyperfunction theory), so bear that in mind while reading his defense of rapamycin. His view is that it is absolutely the case that aging can be significantly impacted by intervening in genetic programs thought to be driving it, and suitable drugs are the first step on that road. This is the reverse of other side of the aging research community who see aging as caused by accumulated damage, and the accompanying metabolic changes as a reaction to that damage rather than its cause. Nonetheless there are some interesting arguments made here:

Making headlines, a thought-provocative paper by Neff, Ehninger and coworkers claims that rapamycin extends life span but has limited effects on aging. How is that possibly possible? And what is aging if not an increase of the probability of death with age. I discuss that the JCI paper actually shows that rapamycin slows aging and also extends lifespan regardless of its direct anti-cancer activities.

Found by chance on the mystical Easter island, the anti-aging drug rapamycin gave birth to numerous myths. This time, it is claimed that rapamycin prolongs lifespan and prevents aging-associated changes by aging-independent mechanisms, not by affecting aging itself. But what is then aging itself. Aging is an exponential increase of the probability of death with age. No one has died from health or without a cause. Most elderly humans die from age-related diseases, which are also called "natural causes", if a precise diagnosis is unnecessary. In mammals, death from aging means death from age-related diseases. Not only humans and other mammals but also aging worms and flies die from pathologies.

Age-related diseases are biomarkers of aging. The most common are cardiovascular diseases (associated with atherosclerosis, hypertension and cardiac hypertrophy), cancer, diabetes (and other complications of metabolic syndrome), Alzheimer and Parkinson diseases, macular degeneration and so on. Many manifestations of aging are not considered as diseases because they either develop in everyone (e.g. female menopause. The distinction is arbitrarily. For example, cancer-prone transgenic mice can exclusively die from cancer but still cancer is a disease.

Aging processes do not spring from nothing. They are continuations of normal cellular, tissue, organ and system functions in young animals. Unless miracle is possible, rapamycin must affect the same processes in old and young animals. And it does. Rapamycin extends life span independently of its anti-cancer effect and prevents cancer by slowing down aging. If rapamycin indeed prevents cancer by slowing aging (not by killing cancer cells), the prevention must be started before cancer is initiated. In other words, if rapamycin treatment is started too late in life, then its anti-cancer effect will be blunted. This was shown in cancer-prone p53+/- mice. The same was shown by Neff et al: rapamycin did not prevent cancer when the treatment was started at middle and old age. Thus, the JCI study confirms the notion that rapamycin delays cancer by slowing aging. Anti-cancer effects simply cannot be responsible for life extension by rapamycin.


Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.