Ahiawodzi Peter, Fitzpatrick Annette L, Djousse Luc, Ix Joachim H, Kizer Jorge R, Mukamal Kenneth J
Department of Public Health, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA.
Departments of Family Medicine, Epidemiology, and Global Health, University of Washington, Seattle, WA, USA.
Metabol Open. 2020 Sep 7;8:100058. doi: 10.1016/j.metop.2020.100058. eCollection 2020 Dec.
Telomeres shorten as organisms age, placing limits on cell proliferation and serving as a marker of biological aging. Non-esterified fatty acids (NEFAs) are a key mediator of age-related metabolic abnormalities. We aimed to determine if NEFAs are associated with telomere length in community-living older adults.
We cross-sectionally studied 1648 participants of the Cardiovascular Health Study (CHS) who underwent concomitant telomere length measurement from a sample of 4715 participants who underwent measurement of circulating total fasting NEFAs in stored specimens from their 1992-3 clinic visit. We used linear regression and inverse probability weighting to model telomere length as a function of NEFAs with adjustment for age, gender, race, clinic, BMI, marital status, smoking status, alcohol intake, diabetes status, years of education, hypertension status, prevalent cardiovascular disease, C-reactive protein, total adiponectin, albumin, fetuin-A, fasting insulin, eGFR, total cholesterol, HDL-cholesterol, triglycerides, and general health status.
Higher NEFAs were significantly associated with shorter telomere length, after adjusting for age, gender, race, and clinic site (β = -0.034; SE = 0.015; = 0.02). Estimates remained similar in fully adjusted models where each SD of NEFA increment was associated with 0.042 kilobase (kb) pairs shorter telomere length (standard error = 0.016; = 0.007); for comparison the coefficient for a single year of age in the same model was -0.017. These results were similar in strata of sex, and waist circumference although they tended to be strongest among participants in the youngest tertile of age (β = -0.079; SE = 0.029; P = 0.01).
In this population-based cohort of community-living elders, we observed a significant inverse association between NEFAs and telomere length. If confirmed, NEFAs may represent a promising target for interventions to slow biological aging.
随着生物体衰老,端粒会缩短,这限制了细胞增殖,并作为生物衰老的一个标志。非酯化脂肪酸(NEFAs)是与年龄相关的代谢异常的关键介质。我们旨在确定NEFAs是否与社区居住的老年人的端粒长度相关。
我们对心血管健康研究(CHS)的1648名参与者进行了横断面研究,这些参与者同时进行了端粒长度测量,该样本来自4715名参与者,他们在1992 - 1993年诊所就诊时,对储存样本中的循环总空腹NEFAs进行了测量。我们使用线性回归和逆概率加权法,将端粒长度作为NEFAs的函数进行建模,并对年龄、性别、种族、诊所、体重指数、婚姻状况、吸烟状况、饮酒量、糖尿病状况、受教育年限、高血压状况、心血管疾病患病率、C反应蛋白、总脂联素、白蛋白、胎球蛋白A、空腹胰岛素、估算肾小球滤过率、总胆固醇、高密度脂蛋白胆固醇、甘油三酯和总体健康状况进行了调整。
在调整了年龄、性别、种族和诊所地点后,较高的NEFAs与较短的端粒长度显著相关(β = -0.034;标准误 = 0.015;P = 0.02)。在完全调整的模型中,估计值仍然相似,其中NEFA每增加一个标准差,端粒长度就会缩短0.042千碱基对(kb)(标准误 = 0.016;P = 0.007);作为比较,同一样模型中年龄每增加一岁的系数为 -0.017。这些结果在性别和腰围分层中相似,尽管在最年轻年龄三分位数的参与者中往往最为显著(β = -0.079;标准误 = 0.029;P = 0.01)。
在这个基于人群的社区居住老年人队列中,我们观察到NEFAs与端粒长度之间存在显著的负相关。如果得到证实,NEFAs可能代表了减缓生物衰老干预措施的一个有前景的靶点。