A look at Rapamycin the life extending drug with some serious drawbacks.

If any drug has performed consistently and unequivocally well in anti-aging trials, it’s rapamycin. Dr. Matt Kaeberlein’s Dog Aging Project is among the most recent trials investigating its longevity-promoting potential in mammals, but it’s also been the subject of numerous trials in mice, worms, flies and yeast. And although it acts through a mechanism which has been most closely associated cancer prevention, this drug appears to stave off all maladies related to aging.

Even more encouraging are the indications that it could be beneficial well into old age. Trials done in the National Aging Institute’s ITP, a testing protocol that collects its data from three independent labs, found that when mice started rapamycin treatment at 600 days old (roughly 60 in human years), they lived an average of 11% longer than control counterparts. Longevity interventions that hold up well even in late-life are few and far between, and even the traditionally successful method of caloric restriction has limited utility when begun late.

Coincidentally, some think that caloric restriction works via the same pathway as rapamycin: by inhibiting the enzyme mTOR. Among its numerous functions, mTOR helps to drive cell growth and proliferation. Halting out of control cell division is key to cancer prevention, and so it’s not too surprising that rapamycin treatment counters development of certain types of tumors by inhibiting mTOR. It can have detrimental effects on nutrient sensing, the factor behind metabolic diseases like diabetes, by promoting activation of insulin receptors. And since mTOR is responsible for increasing energy consumption and cellular metabolism, it can also produce oxidative stress by way of the free radicals created by overactive mitochondria.

A review of senescent cell removal therapies.

Aging at the cellular level is called “cell senescence”, and it contributes profoundly to whole-body aging. The most promising near-term prospects for a leap in human life expectancy come from drugs that eliminate senescent cells. Programs in universities and pharmaceutical labs around the world are racing to develop “senolytic” drugs, defined as agents that can kill senescent cells with minimal harm to normal cells.

Apoptosis is cell suicide, and (from the perspective of the full organism) it’s the best thing that can happen to senescent cells. The authors of this newest Dutch study ask how it is that senescent cells escape apoptosis.

FOXO is a protein that controls gene expression, a master transcription factor associated with aging and development. (It is the homolog in mammals of the pivotal life extension protein first identified in worms as DAF16 in the 1990s.) FOXO4 activiation in a cell can block apoptosis. P53 is the most common trigger of apoptosis, the first protein biochemists usually think of in connection with apoptosis. P53 has multiple functions in the cell nucleus, but as a trigger for apoptosis, it works through the mitochondria. FOXO4 binds to p53 and blocks its induction of apoptosis.

DNA damage reversed in mice. Humans are next.

Scientists reverse aging in mice by repairing DNA damage. Human trials are on the cards in the next six months.