School of Public Health, Fudan University, 130 Dongan Road, Shanghai, 200032, China.
Shanghai Municipal Center for Disease Control and Prevention, Shanghai, 200336, China.
Geroscience. 2021 Apr;43(2):645-654. doi: 10.1007/s11357-020-00320-y. Epub 2021 Jan 19.
It is well established from previous cross-sectional studies that telomeres shorten with age. However, due to a considerable inter-individual variation in telomere length (TL), its relationship with biological aging is difficult to unpick. Longitudinal repeated assessments of TL changes within individuals should augment our understanding of TL dynamics in aging. This study disentangles within- and inter-individual effects of age on leukocyte telomere length (LTL) dynamics in a large population-based cohort of older adults. A total of 4053 subjects aged 50 and older from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Relative LTL (T/S ratio) was measured at baseline (2009-2010) and follow-up (2017-2018) by quantitative real-time polymerase chain reaction. We used linear random slope models to analyze LTL dynamics in relation to age and sex and within-subject centering method to distinguish within- versus between-subject effects. We observed LTL shortening in 66.32%, maintenance in 11.23%, and elongation in 22.45% of the study participants. LTL declined significantly with age both cross-sectionally and longitudinally. More importantly, the longitudinal decline in LTL was much greater than the cross-sectional decline (- 0.017 (p < 0.001) versus - 0.002 (p < 0.001) per year). Furthermore, women had a lower within-subject LTL shortening rate than men (- 0.014 versus - 0.020 per year, p < 0.001). The within-individual longitudinal decline in LTL was much greater than the inter-individual cross-sectional decline, indicating that chronological age might impose a greater impact on LTL shortening than other influencing factors combined. Moreover, women showed a lower within-individual LTL shortening rate than men.
已有大量横断面研究证实端粒会随年龄增长而缩短。然而，由于端粒长度（TL）个体间存在较大差异，其与生物衰老的关系难以厘清。对个体内 TL 变化的纵向重复评估应增进我们对衰老过程中端粒动态的理解。本研究在一个大型基于人群的老年队列中，剖析了年龄对白细胞端粒长度（LTL）动态变化的个体内和个体间效应。本研究共纳入了来自世界卫生组织老龄化和成人健康研究（SAGE）上海队列的 4053 名 50 岁及以上的受试者。在基线（2009-2010 年）和随访（2017-2018 年）时，通过实时定量聚合酶链反应测定相对端粒长度（T/S 比值）。我们采用线性随机斜率模型分析了端粒长度与年龄和性别之间的动态变化关系，并采用个体内中心化方法来区分个体内和个体间效应。我们发现，66.32%的研究参与者的端粒长度缩短，11.23%的端粒长度维持不变，22.45%的端粒长度延长。端粒长度在横断面和纵向上均随年龄显著缩短。更重要的是，端粒长度的纵向下降幅度明显大于横断面下降幅度（-0.017（p<0.001）与-0.002（p<0.001）/年）。此外，女性的个体内端粒长度缩短率低于男性（-0.014 与-0.020/年，p<0.001）。个体内纵向端粒长度下降幅度明显大于个体间横断面下降幅度，表明与其他影响因素综合作用相比，时间年龄对端粒缩短的影响可能更大。此外，女性的个体内端粒长度缩短率低于男性。
