title: Time to talk SENS: critiquing the immutability of human aging.
abstract: Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus accumulates. This accumulating damage ultimately drives age-related degeneration. Interventions can be designed at all three stages. However, intervention in metabolism can only modestly postpone pathology, because production of toxins is so intrinsic a property of metabolic processes that greatly reducing that production would entail fundamental redesign of those processes. Similarly, intervention in pathology is a "losing battle" if the damage that drives it is accumulating unabated. By contrast, intervention to remove the accumulating damage would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely. We survey the major categories of such damage and the ways in which, with current or foreseeable biotechnology, they could be reversed. Such ways exist in all cases, implying that indefinite postponement of aging--which we term "engineered negligible senescence"--may be within sight. Given the major demographic consequences if it came about, this possibility merits urgent debate.
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, UK. ag24@gen.cam.ac.uk
authors.forename: Aubrey D N J
authors.initials: AD
authors.lastname: de Grey
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Ames
authors.forename: Julie K
authors.initials: JK
authors.lastname: Andersen
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Heward
authors.forename: Roger J M
authors.initials: RJ
authors.lastname: McCarter
authors.forename: Gregory
authors.initials: G
authors.lastname: Stock
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008017:Life Expectancy