Cellular Senescence Biomarker p16INK4a+ Cell Burden in Thigh Adipose is Associated With Poor Physical Function in Older Women

J Gerontol A Biol Sci Med Sci. 2018 Jun 14;73(7):939-945. doi: 10.1093/gerona/glx134.

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 p16INK4a-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/m2). p16INK4a+ 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 p16INK4a+ 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). p16INK4a+ cell abundance was lower following the intervention (pre: 5.47 ± 3.4%, post: 2.17 ± 1.1% count p16INK4a+ cells, p ≤ .05).

Conclusions: These results provide proof-of-concept that p16INK4a+ cells in thigh adipose are associated with physical function, and may be sensitive to change with RT ± CR in overweight/obese older women.

Publication types

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

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Adipose Tissue / physiopathology*
  • Adiposity
  • Aged
  • Aging / metabolism*
  • Aging / pathology
  • Aging / physiology*
  • Biomarkers / metabolism
  • Body Mass Index
  • Caloric Restriction
  • Cellular Senescence
  • Cross-Sectional Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Female
  • Frail Elderly
  • Frailty / metabolism
  • Frailty / pathology
  • Frailty / physiopathology
  • Humans
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / physiopathology
  • Overweight / metabolism
  • Overweight / pathology
  • Overweight / physiopathology
  • Physical Functional Performance
  • Resistance Training
  • Thigh

Substances

  • Biomarkers
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16