This fascinating open access paper investigates a role in aging for DNA fragments that have escaped the cell nucleus, for underlying reasons probably related to stochastic nuclear DNA damage, but yet to be comprehensively explored. They may contribute to cellular senescence and the chronic inflammation generated by senescent cells, and this is accomplished by activating an innate immune sensor, cGAS-STING. This innate immune mechanism is already strongly linked to the bad behavior of senescent cells. The most interesting portion of the work here is the prospect for cleaning up extranuclear DNA fragments via some form of molecular therapy, and therefore dampening the consequence. The researchers demonstrate a proof of principle, and it would be interesting to see this explored further in naturally aging mice.
Subclinical but heightened inflammation is observed in aging tissues, and in the blood of older adults in large epidemiologic studies, with consistently higher basal levels of C-reactive protein and abundant pro-inflammatory cytokines. Such alteration is often viewed as non-cell autonomous, for example senescent cells, which increase with aging, may modulate inflammation through secretion of cytokines (i.e., senescence-associated secretory phenotype, SASP. The
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