title: Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options.
abstract: Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, loss of proteostasis, cellular senescence and adult stem cell exhaustion. However, whether and how these instigators of aging interrelate or whether they have one root cause is currently largely unknown. Rare human progeroid syndromes and corresponding mouse mutants with resolved genetic defects highlight the dominant importance of genome maintenance for aging. A second class of aging-related disorders reveals a cross connection with metabolism. As genome maintenance and metabolism are closely interconnected, they may constitute the main underlying biology of aging. This review focuses on the role of genome stability in aging, its crosstalk with metabolism, and options for nutritional and/or pharmaceutical interventions that delay age-related pathology.
authors.affiliation: Department of Genetics, Erasmus University Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands; email: w.vermeij@erasmusmc.nl , j.hoeijmakers@erasmusmc.nl , j.pothof@erasmusmc.nl.
authors.forename: Wilbert P
authors.initials: WP
authors.lastname: Vermeij
authors.affiliation: Department of Genetics, Erasmus University Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands; email: w.vermeij@erasmusmc.nl , j.hoeijmakers@erasmusmc.nl , j.pothof@erasmusmc.nl.
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.affiliation: Department of Genetics, Erasmus University Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands; email: w.vermeij@erasmusmc.nl , j.hoeijmakers@erasmusmc.nl , j.pothof@erasmusmc.nl.
authors.forename: Joris
authors.initials: J
authors.lastname: Pothof
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D051379:Mice; D013577:Syndrome
keywords: DNA damage; DNA repair; age-related diseases; antiaging interventions; frailty; progeria