title: How does proliferative homeostasis change with age? What causes it and how does it contribute to aging?
abstract: The notion that there might be a cellular basis for aging stems from research that began several decades ago and was proposed to explain the loss of proliferative homeostasis, which is a hallmark of complex animals. Recent years have seen growing support for the idea that two cell fates-apoptosis and cellular senescence, both now well-established tumor suppressor mechanisms-may be important drivers of aging phenotypes and age-related disease. However, there remain many unanswered questions, some quite basic, about how these processes change with age and how they might contribute to aging. It is now clear that failures in apoptosis or senescence can result in hyperproliferative diseases such as cancer. Less is known about whether and how increased apoptosis or senescence can cause tissue degeneration and aging. In addition, there is now a growing recognition that cellular senescence can have cell-nonautonomous effects within tissues. New molecular tools and model organisms, some already on the horizon, will need to be developed to better understand the roles of apoptosis and cellular senescence in age-associated changes in proliferative homeostasis.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA. jcampisi@buckinstitute.org
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
authors.forename: John
authors.initials: J
authors.lastname: Sedivy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics; D051379:Mice; D023421:Models, Animal; D008967:Molecular Biology; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012680:Sensitivity and Specificity; D013234:Stem Cells / Q000502:physiology