Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain

Matthew T Buckley; Eric D Sun; Benson M George; Ling Liu; Nicholas Schaum; Lucy Xu; Jaime M Reyes; Margaret A Goodell; Irving L Weissman; Tony Wyss-Coray; Thomas A Rando; Anne Brunet

doi:10.1038/s43587-022-00335-4

Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain

Nat Aging. 2023 Jan;3(1):121-137. doi: 10.1038/s43587-022-00335-4. Epub 2022 Dec 19.

Authors

Matthew T Buckley^#^{1

2}, Eric D Sun^#^{1

3}, Benson M George^{4

5}, Ling Liu^{6

7}, Nicholas Schaum⁶, Lucy Xu^{1

8}, Jaime M Reyes^{9

10

11}, Margaret A Goodell^{9

10

11}, Irving L Weissman^{5

12

13

14}, Tony Wyss-Coray^{6

15

16}, Thomas A Rando^{6

16

17

7

18}, Anne Brunet^{19

20

21}

Affiliations

¹ Department of Genetics, Stanford University, Stanford, CA, USA.
² Genetics Graduate Program, Stanford University, Stanford, CA, USA.
³ Biomedical Informatics Graduate Program, Stanford University, Stanford, CA, USA.
⁴ Stanford Medical Scientist Training Program, Stanford University, Stanford, CA, USA.
⁵ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
⁶ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Department of Neurology, UCLA, Los Angeles, CA, USA.
⁸ Department of Biology, Stanford University, Stanford, CA, USA.
⁹ Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
¹⁰ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
¹¹ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
¹² Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA, USA.
¹³ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
¹⁴ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁵ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
¹⁶ Glenn Center for the Biology of Aging, Stanford University, Stanford, CA, USA.
¹⁷ Neurology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
¹⁸ Broad Stem Cell Research Center, UCLA, Los Angeles, CA, USA.
¹⁹ Department of Genetics, Stanford University, Stanford, CA, USA. abrunet1@stanford.edu.
²⁰ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. abrunet1@stanford.edu.
²¹ Glenn Center for the Biology of Aging, Stanford University, Stanford, CA, USA. abrunet1@stanford.edu.

^# Contributed equally.

Abstract

The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic regions for two interventions-heterochronic parabiosis and exercise. Aging clocks revealed that heterochronic parabiosis and exercise reverse transcriptomic aging in neurogenic regions, but in different ways. This study represents the first development of high-resolution aging clocks from single-cell transcriptomic data and demonstrates their application to quantify transcriptomic rejuvenation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aging* / genetics
Animals
Brain
Cellular Senescence
Mice
Neurogenesis
Rejuvenation*

Abstract

Publication types

MeSH terms

Grants and funding