A View of Aging Centered Around Mutation and Senescence
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Many researchers see stochastic mutational damage to nuclear DNA as an important mechanism in aging, above and beyond its contribution to cancer risk. The challenge has always been that there don’t seem to be enough mutations to explain significant harm, if the harm remains restricted to only the cell in which the mutation occurs. One way to explain how DNA damage causes more general issues is through clonal expansion of detrimental mutations that occur in stem and progenitor cells. Another possible explanation, presently being energetically explored by the research community, is that DNA damage can cause cellular senescence. In this case, just a few senescent cells can cause outsized amounts of harm in surrounding tissue through the potent mix of signals they secrete: generating inflammation, remodeling the extracellular matrix, changing the behavior of other cells for the worse, and so on. We’ll be seeing a great many papers like this one in the years ahead, I think.

stochastic mutational damage to nuclear DNAclonal expansion of detrimental mutationsstemprogenitorcellular senescencepotent mix of signalsextracellular matrix

During an organism’s lifetime, cells are constantly exposed to exogenous and endogenous stressful agents. Cells can cope with these stressors by various response mechanisms, or in case of irreversible

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