title: The roles of cellular and organismal aging in the development of late-onset maladies.
abstract: Numerous disorders, including neurodegenerative diseases and certain types of cancer, manifest late in life. This common feature raises the prospect that an aging-associated decline in the activity of cellular and organismal maintenance mechanisms enables the emergence of these maladies in late life stages. Accordingly, the alteration of aging bears the promise of harnessing the mechanisms that protect the young organism to prevent illness in the elderly. The identification of aging-regulatory pathways has enabled scrutiny of this hypothesis and revealed that the alteration of aging protects invertebrates and mammals from toxic protein aggregation linked to neurodegeneration and from cancer. Here we review the current knowledge on the regulation of aging at the cellular and organismal levels, delineate the mechanistic links between aging and late-onset disorders, describe efforts to develop compounds that protect from these maladies by selectively manipulating aging, and discuss future research directions and possible therapeutic implications of this approach.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University School of Medicine, 91120 Jerusalem, Israel; email: ehudc@ekmd.huji.ac.il.
authors.forename: Filipa
authors.initials: F
authors.lastname: Carvalhal Marques
authors.forename: Yuli
authors.initials: Y
authors.lastname: Volovik
authors.forename: Ehud
authors.initials: E
authors.lastname: Cohen
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology
keywords: dietary restriction; insulin/IGF-1 signaling; neurodegeneration; proteostasis; proteotoxicity; stress resistance