Critiquing SENS on Nuclear DNA Damage

Ben Best here offers a critique of SENS, the Strategies for Engineered Negligible Senescence assembled by Aubrey de Grey, based on the absence of nuclear DNA damage from the list of things to repair: "Dr. de Grey asserts that repairing aging damage is a more effective approach than attempting to slow or prevent aging, and I agree with him. Being an ardent supporter of SENS has not stopped me from simultaneously being a critic of aspects of his program that I think are flawed or deficient. I will attempt to outline some of my criticisms in simple language, assuming that my readers have some knowledge of basic science. ... [a] fundamental concern that I have that a significant form of aging damage may be being ignored by SENS. ... There are many types of DNA damage, but for the purposes of this essay I will focus on breakage of both DNA strands - resulting in a gap in a chromosome. There are two mechanisms for repairing double-strand DNA breaks: Homologous Recombination (HR) and Non-Homologous End-Joining (NHEJ). HR usually results in perfect repair, but HR can only operate when cells are dividing. NHEJ is the more frequent form of double-strand break repair, but it is error-prone. NHEJ is the only DNA repair mechanism available for non-dividing cells. Even in cells that divide, 75% of double-strand breaks are repaired by NHEJ. ... It is hard to believe that it could be a coincidence that the most notorious 'accelerated aging' diseases are due to defective DNA repair. ... Nuclear DNA damage typically leads to mutation or DNA repair - or apoptosis or cellular senescence when DNA repair fails (a mechanism that is believed to have evolved for protection against cancer). But not all DNA damage is repaired, and NHEJ repair is often defective. Accumulating DNA damage and mutation can lead to increasingly dysfunctional cells." Everyone in the community should have a go at critiquing SENS - because doing so forces you to do some digging and think it through for yourself, at which point you'll find that many aspects of biotechnology and human cellular biology are not as intimidating or as hard to understand as they might appear at a distance.



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