Mechanisms of Hippocampal Aging and the Potential for Rejuvenation

Annu Rev Neurosci. 2017 Jul 25;40:251-272. doi: 10.1146/annurev-neuro-072116-031357. Epub 2017 Apr 24.


The past two decades have seen remarkable progress in our understanding of the multifactorial drivers of hippocampal aging and cognitive decline. Recent findings have also raised the possibility of functional rejuvenation in the aged hippocampus. In this review, we aim to synthesize the mechanisms that drive hippocampal aging and evaluate critically the potential for rejuvenation. We discuss the functional changes in synaptic plasticity and regenerative potential of the aged hippocampus, followed by mechanisms of microglia aging, and assess the cross talk between these proaging processes. We then examine proyouth interventions that demonstrate significant promise in reversing age-related impairments in the hippocampus and, finally, attempt to look ahead toward novel therapeutics for brain aging.

Keywords: adult neurogenesis; exercise; heterochronic parabiosis; microglia; neuroinflammation; synaptic plasticity.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Hippocampus / physiology*
  • Humans
  • Neurogenesis / physiology
  • Neuronal Plasticity / physiology
  • Rejuvenation / physiology*