In Search of Drugs That Modulate Aging
Where the mainstream of aging research is thinking about extending healthy life, these researchers are near entirely focused on traditional drug discovery and development with the aim of gently slowing the rate of aging. This will no doubt result in a great deal of new knowledge in the course of better understanding the molecular biology of nature means of life extension, such as calorie restriction, but it doesn't stand much of a chance of producing technologies that will allow you and I to live significantly longer. A drug to slightly slow aging that emerges 20 years from now will of little use to people already old, and only of marginal use for everyone else.
An important task to undertake today is convincing the mainstream of aging research to adopt the SENS view on aging: to work on rejuvenation therapies that repair the known underlying damage of aging, a much more effective approach that will result in treatments that do help the elderly and do significantly extend healthy life spans.
Once a backwater in medical sciences, aging research has emerged and now threatens to take the forefront. This dramatic change of stature is driven from 3 major events. First and foremost, the world is rapidly getting old. Never before have we lived in a demographic environment like today, and the trends will continue such that 20% percent of the global population of 9 billion will be over the age of 60 by 2050. Given current trends of sharply increasing chronic disease incidence, economic disaster from the impending silver tsunami may be ahead.A second major driver on the rise is the dramatic progress that aging research has made using invertebrate models such as worms, flies, and yeast. Genetic approaches using these organisms have led to hundreds of aging genes and, perhaps surprisingly, strong evidence of evolutionary conservation among longevity pathways between disparate species, including mammals. Current studies suggest that this conservation may extend to humans.
Finally, small molecules such as rapamycin and resveratrol have been identified that slow aging in model organisms, although only rapamycin to date impacts longevity in mice. The potential now exists to delay human aging, whether it is through known classes of small molecules or a plethora of emerging ones. But how can a drug that slows aging become approved and make it to market when aging is not defined as a disease? Here, we discuss the strategies to translate discoveries from aging research into drugs. Will aging research lead to novel therapies toward chronic disease, prevention of disease or be targeted directly at extending lifespan?
At least in mice resveratrol seems to extend max lifespan in obese(bringing it to normal nonobese levels), in alzheimer's like genetically altered mice and in senescent acelerated mice. Why it failed in a few studies to raise lifespan in normal mice is a good question, I would want to see more studies before ruling out the possibility.
As for other drugs related to aging there was the promising Bexarotene example, although there's been a failure to replicate it, if it's replicated it could show an interesting possibility. Originally this drug seemed to clear 50% of alzheimer's like plaques in 72hrs, suggesting that ramped up the existing repair and maintenance mechanisms could not only deal with the aging related accumulation of damage but could reverse it.
For some things like mitochondrial quality and intracellular molecular garbage, some mechanisms must exist that maintain long lived high metabolic activity single cells functional for what seems like indefinite periods. Whether it be some unknown means of processing molecular garbage or some means of exporting it, something must be in place. And if it is in place in long lived cells the same genes lie either dormant or less active in the rest of the body.