The geroscience hypothesis proposes that underlying biological processes, such as the accumulation of senescent cells, have deleterious effects on multiple tissues and increase the risk of many chronic conditions with aging. Senescent cells produce heterogenous biomarkers, also called senescence-associated secretory phenotype (SASP). Circulating concentrations of senescence biomarkers may reflect an underlying burden of senescent cells in various tissues. Plasma levels of these proteins have been associated with increased mortality and poorer physical function. The associations of them with the incidence of major age-related conditions including heart failure, cardiovascular disease, stroke, and dementia, have not been studied. We measured 35 senescence biomarkers in baseline plasma samples from 1678 participants aged 70–79 years old in the longitudinal Health ABC cohort study. Clinical outcomes were ascertained and validated over an average 11.5 year follow-up. In models adjusted for age, sex, and race, higher levels of most of senescence biomarkers were associated with increased risk of all-cause mortality, mobility limitation, and heart failure. Several were also associated with an increased risk of coronary heart disease, stroke, and dementia. Very few were associated with the risk of cancer. Proteins that were selected by Lasso regression for each outcome that commonly included GDF15 and IL6, significantly improved the prediction of mortality, mobility limitation, and heart failure compared with age, sex, and race alone. These results indicate that levels of senescence biomarkers predict an increased risk of several age-related clinical outcomes and may identify individuals most likely to benefit from senotherapeutics.

老年科学假说提出，潜在的生物过程，例如衰老细胞的积累，对多种组织有有害影响，并随着衰老而增加许多慢性病的风险。衰老细胞产生异质性生物标志物，也称为衰老相关分泌表型 （SASP）。衰老生物标志物的循环浓度可能反映了各种组织中衰老细胞的潜在负担。这些蛋白质的血浆水平与死亡率增加和身体机能变差有关。尚未研究它们与主要年龄相关疾病（包括心力衰竭、心血管疾病、中风和痴呆）发病率的关联。在纵向健康 ABC 队列研究中，我们测量了 1678 名年龄在 70-79 岁之间的参与者的基线血浆样本中的 35 种衰老生物标志物。在平均 11.5 年的随访中确定和验证了临床结果。在根据年龄、性别和种族调整的模型中，大多数衰老生物标志物的较高水平的与全因死亡、活动受限和心力衰竭的风险增加有关。一些还与冠心病、中风和痴呆的风险增加有关。极少数与癌症风险相关。与 单独使用年龄、性别和种族相比，通过 Lasso 回归为每个结果（通常包括 GDF15 和 IL6）选择的蛋白质显着改善了对死亡率、活动受限和心力衰竭的预测。这些结果表明，衰老生物标志物水平可预测多种与年龄相关的临床结果的风险增加，并可能确定最有可能从新疗法中受益的个体。