July 8th, 2026
The point of studying the biochemistry of very long-lived humans is to try to better understand which of the many underlying mechanisms of damage and dysfunction that drive degenerative aging are the most important and thus should be prioritized for the development of therapies. One can look at the differences in the sequences of proteins, expression of proteins, and the operation of metabolism and try to infer why those differences tend to exist more often in long-lived individuals, try to make a link to a known form of damage. The point is not to to try to emulate the specific biochemistry of long-lived individuals: all that will happen as a result of that is a modest decrease in pace of aging, while one will still wind up frail, greatly impacted by degeneration, and with a very high mortality rate. It is a small gain. We would like to engineer larger gains.
In today's open access paper, researchers find that SIRT6 variants that are more common in centenarians are protective because they reduce the burden of senescent cells in aged tissues. The response to that finding should be to ramp up development of more and better senotherapeutic research programs with the goal of selectively removing senescent cells from the aging body on an ongoing basis, or at the very least halting the harmful signaling that is the primary mechanism by which lingering senescent cells are disruptive to structure and function in surrounding tissues. The response should not be to deliver better versions of SIRT6 into patients via gene therapy, as this will be far less beneficial.
