Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, United States of America; Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Boston, MA 02114, United States of America.
Department of Psychological and Brain Sciences, University of California, Santa Barbara 93111, United States of America.
Horm Behav. 2024 Sep;165:105631. doi: 10.1016/j.yhbeh.2024.105631. Epub 2024 Sep 3.
Telomere length (TL) is an important cellular marker of biological aging impacting the brain and heart. However, how it is related to the brain (e.g., cognitive function and neuroanatomic architecture), and how these relationships may vary by sex and reproductive status, is not well established. Here we assessed the association between leukocyte TL and memory circuitry regional brain volumes and memory performance in early midlife, in relation to sex and reproductive status. Participants (N = 198; 95 females, 103 males; ages 45-55) underwent structural MRI and neuropsychological assessments of verbal, associative, and working memory. Overall, shorter TL was associated with smaller white matter volume in the parahippocampal gyrus and dorsolateral prefrontal cortex. In males, shorter TL was associated with worse working memory performance and corresponding smaller white matter volumes in the parahippocampal gyrus, anterior cingulate cortex, and dorsolateral prefrontal cortex. In females, the impact of cellular aging was revealed over the menopausal transition. In postmenopausal females, shorter TL was associated with poor associative memory performance and smaller grey matter volume in the right hippocampus. In contrast, TL was not related to memory performance or grey and white matter volumes in any memory circuitry region in pre/perimenopausal females. Results demonstrated that shorter TL is associated with worse memory function and smaller volume in memory circuitry regions in early midlife, an association that differs by sex and reproductive status. Taken together, TL may serve as an early indicator of sex-dependent brain abnormalities in early midlife.
端粒长度（TL）是生物衰老的一个重要细胞标志物，它会影响大脑和心脏。然而，TL 与大脑（例如认知功能和神经解剖结构）的关系，以及这些关系如何因性别和生殖状态而异，目前还没有得到很好的确定。在这里，我们评估了白细胞 TL 与记忆回路区域脑体积和记忆表现之间的关系，并探讨了其与性别和生殖状态的关系。研究对象（N=198；95 名女性，103 名男性；年龄 45-55 岁）接受了结构磁共振成像和语言、联想和工作记忆的神经心理学评估。总的来说，较短的 TL 与海马旁回和背外侧前额叶皮质的白质体积较小有关。在男性中，较短的 TL 与较差的工作记忆表现以及海马旁回、前扣带皮层和背外侧前额叶皮质的白质体积较小有关。在女性中，细胞衰老的影响在绝经过渡期间显现出来。在绝经后女性中，较短的 TL 与联想记忆表现较差以及右侧海马灰质体积较小有关。相比之下，TL 与任何记忆回路区域的记忆表现或灰质和白质体积均无相关性。研究结果表明，在中年早期，较短的 TL 与较差的记忆功能和记忆回路区域的体积较小有关，这种关联因性别和生殖状态而异。总之，TL 可能是中年早期性别依赖性大脑异常的早期指标。
