Exercise, APOE genotype, and the evolution of the human lifespan

David A. Raichlen, Gene E. Alexander

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations


Humans have exceptionally long lifespans compared with other mammals. However, our longevity evolved when our ancestors had two copies of the apolipoprotein E (APOE) e{open}4 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 e{open}4, 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.

Original languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalTrends in Neurosciences
Issue number5
StatePublished - May 2014


  • Aerobic fitness
  • Aging
  • Alzheimer's disease
  • Apolipoprotein
  • Dementia
  • Vitamin D

ASJC Scopus subject areas

  • General Neuroscience


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