Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Nat Aging. 2022 Jul;2(7):635-643. doi: 10.1038/s43587-022-00243-7. Epub 2022 Jul 18.
To define metrics of phenotypic aging, it is essential to identify biological and environmental factors that influence the pace of aging. Previous attempts to develop aging metrics were hampered by cross-sectional designs and/or focused on younger populations. In the Baltimore Longitudinal Study of Aging (BLSA), we collected longitudinally across the adult age range a comprehensive list of phenotypes within four domains (body composition, energetics, homeostatic mechanisms and neurodegeneration/neuroplasticity) and functional outcomes. We integrated individual deviations from population trajectories into a global longitudinal phenotypic metric of aging and demonstrate that accelerated longitudinal phenotypic aging is associated with faster physical and cognitive decline, faster accumulation of multimorbidity and shorter survival. These associations are more robust compared with the use of phenotypic and epigenetic measurements at a single time point. Estimation of these metrics required repeated measures of multiple phenotypes over time but may uniquely facilitate the identification of mechanisms driving phenotypic aging and subsequent age-related functional decline.
为了定义表型衰老的指标，确定影响衰老速度的生物和环境因素至关重要。以前开发衰老指标的尝试受到了横断面设计和/或仅关注年轻人群的阻碍。在巴尔的摩纵向衰老研究（BLSA）中，我们在成人年龄范围内收集了四个领域（身体成分、能量学、内稳态机制和神经退行性变/神经可塑性）和功能结果的综合表型列表。我们将个体偏离人群轨迹的情况整合到一个综合的纵向表型衰老指标中，并证明加速的纵向表型衰老与更快的身体和认知能力下降、更多的多种疾病累积和更短的生存时间有关。与在单个时间点使用表型和表观遗传测量相比，这些关联更为稳健。这些指标的估计需要随着时间的推移多次测量多种表型，但可能特别有助于确定驱动表型衰老和随后与年龄相关的功能下降的机制。
