title: Greater organ involution in highly proliferative tissues associated with the early onset and acceleration of ageing in humans.
abstract: Domination of cell proliferation over cell death is a driving force for carcinogenesis, whereas reduced cell proliferation and increased cell death are characteristic of ageing. We employed published data to estimate representative mean values of cell turnover times for 31 different organs and tissues in adult humans and animals (when data in humans were lacking) as well as functional mass loss for 5 organs, accounting for actual mass loss and tissue conversion to fat, in humans over the adult period, age 25 to 70. We found that greater actual and functional mass loss was significantly associated (P=0.001 and P<0.0001, respectively) with the log of shorter cell turnover times. We propose that this is characteristic of stem cell exhaustion and replicative senescence. In addition, we provide quantitative evidence that, in many organs, involution is evident even in young adults. On the basis of published mass measurements of major organs, by analysis of covariance, we identified examples of significant (P≤0.05), accelerated actual or functional mass loss and ageing from early to late adulthood. We hypothesise and quantitatively demonstrate that functional mass loss accelerates with ageing by incorporating the contribution of actual mass loss, tissue conversion to fatty or fibrous tissue, and the presence of apoptotic, necrotic and senescent cells. We propose that mass loss, linked to replicative senescence, is an evolutionary adaptation that effectively limits cancer in young adults, as mass loss is first apparent soon after the end of the growth period, accelerating in the more elderly as biological conditions deviate away from those prevailing in youth, when the selective pressure on pleiotropic genes is greatest.
authors.affiliation: RPRI Branch, AECL, Chalk River Laboratories, Chalk River, ON, Canada. Electronic address: Richard.Richardson@mcgill.ca.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Richardson
authors.affiliation: Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. Electronic address: daallan@ottawahospital.on.ca.
authors.forename: David S
authors.initials: DS
authors.lastname: Allan
authors.affiliation: RPRI Branch, AECL, Chalk River Laboratories, Chalk River, ON, Canada. Electronic address: yleplanet@gmail.com.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Le
mesh_terms: D000375:Aging / Q000473:pathology*; D019588:Aging, Premature / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D006801:Humans; D009929:Organ Size / Q000502:physiology
keywords: Accelerated ageing; Cell death; Evolution; Human; Proliferation