Computational Health Center, Helmholtz Munich, Neuherberg, Germany.
Faculty of Biology, Ludwig Maximilian University, Martinsried, Germany.
Aging Cell. 2023 Oct;22(10):e13957. doi: 10.1111/acel.13957. Epub 2023 Aug 22.
Mechanistic insight into ageing may empower prolonging the lifespan of humans; however, a complete understanding of this process is still lacking despite a plethora of ageing theories. In order to address this, we investigated the association of lifespan with eight phenotypic traits, that is, litter size, body mass, female and male sexual maturity, somatic mutation, heart, respiratory, and metabolic rate. In support of the somatic mutation theory, we analysed 15 mammalian species and their whole-genome sequencing deriving somatic mutation rate, which displayed the strongest negative correlation with lifespan. All remaining phenotypic traits showed almost equivalent strong associations across this mammalian cohort, however, resting heart rate explained additional variance in lifespan. Integrating somatic mutation and resting heart rate boosted the prediction of lifespan, thus highlighting that resting heart rate may either directly influence lifespan, or represents an epiphenomenon for additional lower-level mechanisms, for example, metabolic rate, that are associated with lifespan.
对衰老机制的深入了解可能有助于延长人类的寿命;然而,尽管有大量的衰老理论,但人们对这一过程仍缺乏全面的了解。为了解决这个问题,我们研究了寿命与八个表型特征的关系,即窝仔数、体重、雌性和雄性性成熟、体细胞突变、心脏、呼吸和代谢率。支持体细胞突变理论,我们分析了 15 种哺乳动物及其全基因组测序得出的体细胞突变率,其与寿命呈最强的负相关。在这个哺乳动物队列中,所有其他表型特征都表现出几乎相同的强相关性,但静息心率对寿命的解释有额外的差异。整合体细胞突变和静息心率可以提高对寿命的预测,因此这表明静息心率可能直接影响寿命,或者代表与寿命相关的其他低水平机制(例如代谢率)的附带现象。