Department of Neurology and National Center for Neurological Diseases, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Aging Cell. 2023 Dec;22(12):e13995. doi: 10.1111/acel.13995. Epub 2023 Sep 18.
Identifying the clinical implications and modifiable and unmodifiable factors of aging requires the measurement of biological age (BA) and age gap. Leveraging the biomedical traits involved with physical measures, biochemical assays, genomic data, and cognitive functions from the healthy participants in the UK Biobank, we establish an integrative BA model consisting of multi-dimensional indicators. Accelerated aging (age gap >3.2 years) at baseline is associated incident circulatory diseases, related chronic disorders, all-cause, and cause-specific mortality. We identify 35 modifiable factors for age gap (p < 4.81 × 10 ), where pulmonary functions, body mass, hand grip strength, basal metabolic rate, estimated glomerular filtration rate, and C-reactive protein show the most significant associations. Genetic analyses replicate the possible associations between age gap and health-related outcomes and further identify CST3 as an essential gene for biological aging, which is highly expressed in the brain and is associated with immune and metabolic traits. Our study profiles the landscape of biological aging and provides insights into the preventive strategies and therapeutic targets for aging.
确定临床意义以及可改变和不可改变的衰老因素需要测量生物年龄（BA）和年龄差距。利用英国生物库中健康参与者的身体测量、生化分析、基因组数据和认知功能等与生物医学特征相关的数据，我们建立了一个由多维指标组成的综合 BA 模型。基线时加速衰老（年龄差距>3.2 年）与循环系统疾病、相关慢性疾病、全因和特定原因死亡率的发生有关。我们确定了 35 个与年龄差距相关的可改变因素（p<4.81×10 ），其中肺功能、体重、握力、基础代谢率、估计肾小球滤过率和 C 反应蛋白的相关性最显著。遗传分析复制了年龄差距与健康相关结果之间的可能关联，并进一步确定 CST3 是生物衰老的关键基因，它在大脑中高度表达，并与免疫和代谢特征相关。我们的研究描绘了生物衰老的全景，为衰老的预防策略和治疗靶点提供了新的见解。
