title: Exercise, APOE genotype, and the evolution of the human lifespan.
abstract: Humans have exceptionally long lifespans compared with other mammals. However, our longevity evolved when our ancestors had two copies of the apolipoprotein E (APOE) ɛ4 allele, a genotype that leads to a high risk of Alzheimer's disease (AD), cardiovascular disease, and increased mortality. How did human aging evolve within this genetic constraint? Drawing from neuroscience, anthropology, and brain-imaging research, we propose the hypothesis that the evolution of increased physical activity approximately 2 million years ago served to reduce the amyloid plaque and vascular burden of APOE ɛ4, relaxing genetic constraints on aging. This multidisciplinary approach links human evolution with health and provides a complementary perspective on aging and neurodegenerative disease that may help identify key mechanisms and targets for intervention.
authors.affiliation: School of Anthropology, University of Arizona, Tucson, AZ 85721, USA. Electronic address: raichlen@email.arizona.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Raichlen
authors.affiliation: Department of Psychology, University of Arizona, Tucson AZ 85721, USA; Evelyn F. McKnight Brain Institute, University of Arizona, Tucson AZ 85721, USA; Arizona Alzheimer's Consortium, Phoenix AZ 85006, USA; Neuroscience and Physiological Sciences Graduate Interdisciplinary Programs, University of Arizona, Tucson AZ 85721, USA.
authors.forename: Gene E
authors.initials: GE
authors.lastname: Alexander
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D005075:Biological Evolution; D015444:Exercise / Q000502:physiology*; D005838:Genotype; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics
chemical_list: D001057:Apolipoproteins E
keywords: Alzheimer's disease; aerobic fitness; aging; apolipoprotein; dementia; vitamin D