Fight Aging!

This popular science article on the development and present use of epigenetic clocks mentions the view that the clocks will point the way to a better understanding of the causes of aging. I'm dubious that use of the clocks represents a better way forward to that goal than the approach of implementing the various rejuvenation therapies outlined in the SENS proposals. A potential rejuvenation therapy that affects just one potential root cause of aging in isolation will tell us a lot about the importance and validity of that cause; researchers are learning a great deal from the ability to selectively destroy senescent cells, for example. Even good correlations between epigenetic states and aging will, unfortunately, take a long time to pick apart into knowledge of which mechanisms influence those epigenetic states, and to what degree. All along, the challenge of aging has been that looking without intervening tells us little of the behavior of a very complicated, interacting system of many different degenerative processes.

No one knows entirely why epigenetic clocks work. Some but not all of the genes and molecular pathways involved have been identified, and researchers are still learning how DNA methylation patterns affect the behaviors and health of cells, tissues and organs. Researchers have begun seeking biological correlates for epigenetic aging. Perturbations of the biochemical pathways the body uses to sense its need for nutrients slow aging, they recently discovered, in accordance with the effects of calorie-restricted diets on aging. Derailing the workings of mitochondria speeds it up. The clock also tracks the maturation of stem cells. If these processes are connected at a deeper level, epigenetic clocks may reveal unifying mechanisms for aging, researchers wrote in a 2022 paper.

What those unifying mechanisms might be or why methylation status tracks aging so well, however, is yet to be fully determined. "We don't really know if epigenetic clocks are causally linked with aging." Even if they are, epigenetic clocks are almost certainly measuring only part of what occurs during aging. "Whether they are actually measuring more than a single dimension of biological age is not clear. This is part of the problem here - the conflation of epigenetic age with biological age. Those are not equivalent in my view."

Researchers speculate that the methylation changes reflect a loss of cellular identity with age. All cells in the body have the same DNA, so what makes a liver cell a liver cell and a heart cell a heart cell is the pattern of gene expression, which epigenetics controls. As changes in methylation accumulate with age, some of those controls might be lost, replaced by re-emerging developmental programs that should be switched off. Nonetheless, methylation clocks have limited clinical uses at present. People can buy a readout of their biological age from various commercial sources, but not only are the results often inconsistent, they lack clinical relevance because the clocks were meant for group-level analyses in research. They are not built to be predictive at an individual level.

Link: https://www.quantamagazine.org/epigenetic-clocks-predict-animals-true-biological-age-20220817/