How does the body know how old it is? - Josh Mitteldorf
The mainstream SENS program is premised on the assumption that the body becomes damaged with age, and it is up to us to fix it because the body cannot repair itself. But there has always been a subculture within the SENS community, those of us who believe that the body retains a latent capacity for repair. There exists the possibility that the major hallmarks of senescence can be addressed using signal molecules to instruct the body to behave as though it were a younger age, that appropriate repairs would then be undertaken as they were when the body was young, obviating the need to engineer artificial fixes for each separate form of damage. This possibility deserves investigation, first because there is evidence to support it, and second because, if it pans out, it will offer a shortcut to longevity, achieving SENS goals with less complication and expense. If we take this idea seriously, it implies that the body knows how old it is, and adjusts its biochemistry accordingly - in other words, the metabolism is modulated by an internal clock. Our task is to understand that clock well enough to intervene and reset it to an earlier age. One clock that has been proposed is based on telomere length. In fact, we know that telomere length is the primary aging clock for some protozoans. Over the last decade, we have learned that mortality risk correlates negatively with telomere length (adjusted for age) in man and most other mammals and birds. Evidence that this association is causal is supplied by recent experiments in which telomerase is demonstrated to rejuvenate telomerase knock-out mice. Another candidate aging clock is implemented through gene expression. Experiments with heterochronic parabiosis - linking the circulatory systems of old and young mice - suggest that proteins circulating in the blood may have the power to rejuvenate as well. The documented differences in gene expression between old and young people may be a driver of senescence and not merely a systemic response. Gene expression is controlled locally within a cell by methylation of cytosine, by acetylation of histones, among other modifiers; central control of gene expression from outside the cell is managed through circulating transcription factors. Direct manipulation of a chromosome’s methylation state is not currently possible, but is theoretically feasible. It is an intriguing possibility that the transcription state constitutes a biological clock which can be reset, instructing an old body to behave like a young body.