Human Hippocampal Neurogenesis Persists throughout Aging

  • Cell Stem Cell. 2018 Apr 5;22(4):589-599.e5. doi: 10.1016/j.stem.2018.03.015.
Maura Boldrini  1 ,  Camille A Fulmore  2 ,  Alexandria N Tartt  2 ,  Laika R Simeon  2 ,  Ina Pavlova  3 ,  Verica Poposka  4 ,  Gorazd B Rosoklija  5 ,  Aleksandar Stankov  4 ,  Victoria Arango  6 ,  Andrew J Dwork  7 ,  René Hen  8 ,  J John Mann  6
Affiliations
  • 1. Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Molecular Imaging and Neuropathology, NYS Psychiatric Institute, New York, NY 10032, USA. Electronic address: [email protected].
  • 2. Division of Molecular Imaging and Neuropathology, NYS Psychiatric Institute, New York, NY 10032, USA.
  • 3. Division of Integrative Neuroscience, NYS Psychiatric Institute, New York, NY 10032, USA.
  • 4. Institute for Forensic Medicine, Ss. Cyril & Methodius University, Skopje 1000, Republic of Macedonia.
  • 5. Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Molecular Imaging and Neuropathology, NYS Psychiatric Institute, New York, NY 10032, USA; Macedonian Academy of Sciences & Arts, 2, Ss. Cyril & Methodius University, Skopje 1000, Republic of Macedonia.
  • 6. Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Molecular Imaging and Neuropathology, NYS Psychiatric Institute, New York, NY 10032, USA.
  • 7. Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Division of Molecular Imaging and Neuropathology, NYS Psychiatric Institute, New York, NY 10032, USA; Macedonian Academy of Sciences & Arts, 2, Ss. Cyril & Methodius University, Skopje 1000, Republic of Macedonia.
  • 8. Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA; Department of Pharmacology, Columbia University, New York, NY 10032, USA; Division of Integrative Neuroscience, NYS Psychiatric Institute, New York, NY 10032, USA.
PMID: 29625071 DOI: 10.1016/j.stem.2018.03.015
Abstract

Adult hippocampal neurogenesis declines in aging rodents and primates. Aging humans are thought to exhibit waning neurogenesis and exercise-induced angiogenesis, with a resulting volumetric decrease in the neurogenic hippocampal dentate gyrus (DG) region, although concurrent changes in these parameters are not well studied. Here we assessed whole autopsy hippocampi from healthy human individuals ranging from 14 to 79 years of age. We found similar numbers of intermediate neural progenitors and thousands of immature neurons in the DG, comparable numbers of glia and mature granule neurons, and equivalent DG volume across ages. Nevertheless, older individuals have less angiogenesis and neuroplasticity and a smaller quiescent progenitor pool in anterior-mid DG, with no changes in posterior DG. Thus, healthy older subjects without cognitive impairment, neuropsychiatric disease, or treatment display preserved neurogenesis. It is possible that ongoing hippocampal neurogenesis sustains human-specific cognitive function throughout life and that declines may be linked to compromised cognitive-emotional resilience.

Keywords
Ki-67; NeuN; PSA-NCAM; Sox2; dentate gyrus; doublecortin; granule cells; nestin; neural progenitor; volume.