title: Aging: progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes.
abstract: Different theories posit that aging is caused by molecular damage, genetic programs, continued development, hyperfunction, antagonistic pleiotropy alleles, mutations, trade-offs, incomplete repair, etc. Here, I discuss that these ideas can be conceptually unified as they capture particular facets of aging, while being incomplete. Their respective deleterious effects impact fitness at different levels of biological organization, adjusting progression through aging, rather than causing it. Living is associated with a myriad of deleterious processes, both random and deterministic, which are caused by imperfectness, exhibit cumulative properties, and represent the indirect effects of biological functions at all levels, from simple molecules to systems. From this, I derive the deleteriome, which encompasses cumulative deleterious age-related changes and represents the biological age. The organismal deleteriome consists of the deleteriomes of cells, organs, and systems, which change along roughly synchronized trajectories and may be assessed through biomarkers of aging. Aging is then a progressive decline in fitness due to the increasing deleteriome, adjusted by genetic, environmental, and stochastic processes. This model allows integration of diverse aging concepts, provides insights into the nature of aging, and suggests how lifespan may be adjusted during evolution and in experimental models.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D004777:Environment; D006801:Humans; D055442:Metabolome / Q000235:genetics*; D008954:Models, Biological; D010809:Physical Fitness; D013269:Stochastic Processes
keywords: Aging; Deleteriome; Evolution; Lifespan; Theories of aging