Cellular Senescence Biomarker p16 INK4a + Cell Burden in Thigh Adipose is Associated with Poor Physical Function in Older Women

Jamie N. Justice, Heather Gregory, Tamar Tchkonia, Nathan K. Lebrasseur, James L. Kirkland, Stephen B. Kritchevsky, Barbara J. Nicklas

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background Ample evidence implicates cellular senescence as a contributor to frailty and functional decline in rodents, but considerable effort remains to translate these findings to human aging. Methods We quantified senescence biomarker p16 INK4a -expressing cells in thigh adipose tissue obtained from older women previously enrolled in a 5-month resistance training intervention, with or without caloric restriction (RT ± CR, n = 11 baseline, 8 pre-post-intervention pairs). Women in this subsample were older (72.9 ± 3.4 y) and overweight/obese (body mass index: 30.6 ± 2.4 kg/m 2). p16 INK4a + cells were identified from 12 to 20 random visual fields/sample at 20× magnification (immunohistochemical, nuclear staining) and were present in all adipose samples. Results Cross-sectional associations were observed between p16 INK4a + cell burden and physical function, including grip strength (r = -0.74), 400-m walk time (r = 0.74), 4-m gait speed (r = -0.73), and self-perceived mobility (r = -0.78) (p ≤.05). These relationships remained significant after independent adjustments for age and adiposity (p ≤.05). p16 INK4a + cell abundance was lower following the intervention (pre: 5.47 ± 3.4%, post: 2.17 ± 1.1% count p16 INK4a + cells, p ≤.05). Conclusions These results provide proof-of-concept that p16 INK4a + cells in thigh adipose are associated with physical function, and may be sensitive to change with RT ± CR in overweight/obese older women.

Original languageEnglish (US)
Pages (from-to)939-945
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume73
Issue number7
DOIs
StatePublished - Jun 14 2018

Keywords

  • Biology of aging
  • Caloric restriction
  • Exercise
  • Mobility

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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