Heterochronic parabiosis regulates the extent of cellular senescence in multiple tissues

Matthew J. Yousefzadeh, John E. Wilkinson, Brian Hughes, Namrata Gadela, Warren C. Ladiges, Nam Vo, Laura J. Niedernhofer, Derek M. Huffman, Paul D. Robbins

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

An increase in the burden of senescent cells in tissues with age contributes to driving aging and the onset of age-related diseases. Genetic and pharmacologic elimination of senescent cells extends both health span and life span in mouse models. Heterochronic parabiosis in mice has been used to identify bloodborne, circulating pro- and anti-geronic factors able to drive or slow aging, respectively. However, whether factors in the circulation also regulate senescence is unknown. Here, we measured the expression of senescence and senescence-associated secretory phenotype (SASP) markers in multiple tissues from 4- to 18-month-old male mice that were either isochronically or heterochronically paired for 2 months. In heterochronic parabionts, the age-dependent increase in senescence and SASP marker expression was reduced in old mice exposed to a young environment, while senescence markers were concurrently increased in young heterochronic parabionts. These findings were supported by geropathology analysis using the Geropathology Grading Platform that showed a trend toward reduced hepatic lesions in old heterochronic parabionts. In summary, these results demonstrate that senescence is regulated in part by circulating geronic factors and suggest that one of the possible mediators of the rejuvenating effects with heterochronic parabiosis is through the reduction of the senescent cell burden.

Original languageEnglish (US)
Pages (from-to)951-961
Number of pages11
JournalGeroScience
Volume42
Issue number3
DOIs
StatePublished - Jun 1 2020

Bibliographical note

Funding Information:
This work was supported by R21 AG055026 (DMH), R01 AG044376 (NV), U19 AG056278 (LJN, WCL, PDR), PO1 AG043376 (PDR, LJN), R01 AG063543 (LJN), R56 AG059676 (LJN), R56 AG4059675 (PDR), P01 AG062412 (PDR, LJN)?and the American Federation for Aging Research (DMH), as well as the Einstein Nathan Shock Center (P30 AG038072) and Einstein Cancer Center (P30 CA013330). MJY is supported by The Irene Diamond Fund/American Federation on Aging Research Postdoctoral Transition Award. The authors would like to thank Mariah Witt for editing the manuscript.

Funding Information:
This work was supported by R21 AG055026 (DMH), R01 AG044376 (NV), U19 AG056278 (LJN, WCL, PDR), PO1 AG043376 (PDR, LJN), R01 AG063543 (LJN), R56 AG059676 (LJN), R56 AG4059675 (PDR), P01 AG062412 (PDR, LJN) and the American Federation for Aging Research (DMH), as well as the Einstein Nathan Shock Center (P30 AG038072) and Einstein Cancer Center (P30 CA013330). MJY is supported by The Irene Diamond Fund/American Federation on Aging Research Postdoctoral Transition Award. The authors would like to thank Mariah Witt for editing the manuscript.

Publisher Copyright:
© 2020, American Aging Association.

Keywords

  • Aging
  • Cellular senescence
  • Geropathology
  • Parabiosis
  • SASP

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