Psychology, School of Social Sciences, National Technological University, 48 Nanyang Avenue, Singapore 639798.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore 119559; Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601.
Neurobiol Aging. 2022 Jul;115:60-69. doi: 10.1016/j.neurobiolaging.2022.03.015. Epub 2022 Mar 31.
Telomere shortening is theorized to accelerate biological aging, however, this has not been tested in the brain and cognitive contexts. We used machine learning age-prediction models to determine brain/cognitive age and quantified the degree of accelerated aging as the discrepancy between brain and/or cognitive and chronological ages (i.e., age gap). We hypothesized these age gaps are associated with telomere length (TL). Using healthy participants from the ADNI-3 cohort (N = 196, Age=70.7), we trained age-prediction models using 4 modalities of brain features and cognitive scores, as well as a 'stacked' model combining all brain modalities. Then, these 6 age-prediction models were applied to an independent sample diagnosed with mild cognitive impairment (N = 91, Age=71.3) to determine, for each subject, the model-specific predicted age and age gap. TL was most strongly associated with age gaps from the resting-state functional connectivity model after controlling for confounding variables. Overall, telomere shortening was significantly related to older brain but not cognitive age gaps. In particular, functional relative to structural brain-age gaps, were more strongly implicated in telomere shortening.
端粒缩短被认为会加速生物衰老，但这在大脑和认知环境中尚未得到验证。我们使用机器学习的年龄预测模型来确定大脑/认知年龄，并量化加速衰老的程度，即大脑和/或认知年龄与实际年龄之间的差距（即年龄差距）。我们假设这些年龄差距与端粒长度（TL）有关。使用 ADNI-3 队列中的健康参与者（N=196，年龄=70.7），我们使用 4 种大脑特征和认知评分模式以及结合所有大脑模式的“堆叠”模型来训练年龄预测模型。然后，将这 6 种年龄预测模型应用于独立的轻度认知障碍诊断样本（N=91，年龄=71.3），以确定每个受试者的特定模型预测年龄和年龄差距。在控制混杂变量后，静息态功能连接模型的年龄差距与 TL 最密切相关。总的来说，端粒缩短与大脑衰老而不是认知衰老差距显著相关。特别是，与结构脑年龄差距相比，功能脑年龄差距与端粒缩短的关系更为密切。
