Three links in aging and longevity #2

The Journal of the American Medical Association (JAMA) is one of the top, most influential US medical journals. Now it’s featuring some aging and longevity related articles, out of which we recommend two.

Aging, Cell Senescence, and Chronic Disease

Consistent with cellular senescence being a fundamental process that drives aging and its consequences, senolytics extend life span in mice as well as health span, the period of life when individuals are independent and free of major disability. In mice equivalent to 80-year-old humans, treatment with dasatinib plus quercetin increases survival by 36% and does so without increasing the period of morbidity at the end of life. Senolytics also prevented or alleviated the accelerated onset of physical dysfunction, delayed age-related chronic diseases including cancers, and prevented the decreased survival caused by transplanting senescent cells into mice. In preclinical studies, senolytics delay, prevent, or alleviate multiple age- and senescence-related conditions, including frailty, age-related osteoporosis, and numerous other conditions.

Aging as a Biological Target for Prevention and Therapy

Maximal life expectancy for humans is theorized to be about 115 years. Since the average life expectancy in the United States is currently approximately 80 years old, 35 years have yet to be realized. Centenarians not only live longer than most individuals, they also have an extra 20 to 30 years of health as well as a shorter period of morbidity at the end of life. Some of the mechanisms underlying these extra health years have been discovered. Diet, exercise, and other lifestyle factors can certainly extend health, but to achieve the extraordinarily extended health of centenarians, drugs will likely be necessary. Some of the drugs mentioned above have shown interesting effects in humans. Metformin has shown particular promise in humans as well as in animal models, with published clinical trials and cohort studies reporting substantial reductions (up to 30%) in the risk of type 2 diabetes, cardiovascular disease, and cognitive decline. Similar reductions have been reported for cancer, dementia, and total mortality in observational studies. Metformin has shown an excellent safety profile across more than 60 years of use and is an inexpensive generic drug for treatment of type 2 diabetes.

Finally, a detailed Medium piece on the context and relevance and strategy behind the upcoming metformin trial:

The Safe, Boring, and Extremely Cheap Drug That Could Cure Aging

For all its importance to the emerging science on aging, metformin is a very boring drug. Even the name of the upcoming clinical trial has all the inherent hype of a wet blanket: TAME, an acronym that stands for “Targeting Aging with Metformin.” On its face, it seems unlikely that such a plain little pharmaceutical would be the focus of such a critical trial. Since the patent is expired, no drug company stands to make billions off it, and it’s certainly not going to make anyone live forever. Even Barzilai, who has essentially staked his career on the lifespan-extending prospects of metformin, has a hard time mustering a lot of enthusiasm about the drug itself. “Metformin is basically the first and the weakest drug that will delay aging,” he says.