Sticht Center for Healthy Aging and Alzheimer's Prevention, Internal Medicine - Gerontology and Geriatric Medicine, Wake Forest School of Medicine (WFSM), Winston-Salem, North Carolina.
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota.
J Gerontol A Biol Sci Med Sci. 2018 Jun 14;73(7):939-945. doi: 10.1093/gerona/glx134.
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.
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.
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).
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.
大量证据表明，细胞衰老是导致啮齿动物虚弱和功能下降的原因之一，但仍需要大量努力将这些发现转化为人类衰老。
我们定量测定了先前参加过 5 个月抗阻训练干预（有或无热量限制，RT ± CR，n = 11 个基线，8 个干预前后配对）的老年女性大腿脂肪组织中衰老生物标志物 p16INK4a 表达细胞。该亚组中的女性年龄较大（72.9 ± 3.4 岁）且超重/肥胖（体重指数：30.6 ± 2.4 kg/m2）。p16INK4a+细胞从 12 到 20 个随机视野/样本在 20×放大倍数下（免疫组织化学，核染色）被识别，并且存在于所有脂肪样本中。
在横断面研究中，p16INK4a+细胞负担与身体功能之间存在关联，包括握力（r = -0.74）、400 米步行时间（r = 0.74）、4 米步行速度（r = -0.73）和自我感知的移动能力（r = -0.78）（p ≤.05）。这些关系在独立调整年龄和肥胖程度后仍然显著（p ≤.05）。干预后 p16INK4a+细胞丰度降低（干预前：5.47 ± 3.4%，干预后：2.17 ± 1.1%，p16INK4a+细胞计数，p ≤.05）。
这些结果提供了概念验证，即大腿脂肪中的 p16INK4a+细胞与身体功能相关，并且可能对抗阻训练（RT ± CR）在超重/肥胖老年女性中的变化敏感。
