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

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.