A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice

• DOI: 10.1038/s41467-022-34801-9
• Publication Date: 2022-11-17T12:03:43Z
• Authors: Jie Sun; Ming Wang; Yaqi Zhong; Xuan Ma; Shimin Sun; Chenzhong Xu; Linyuan Peng; Guo Li; Liting Zhang; Zuojun Liu; Ding Ai; Baohua Liu
• Keywords: 0301 basic medicine; Aging; Glycoside Hydrolases; Science; Q; Longevity; Dasatinib; Article; 3. Good health; Mice; Bleomycin; 03 medical and health sciences; Genes, Reporter; Animals; Cellular Senescence

AbstractThe progressive decline of physiological function and the increased risk of age-related diseases challenge healthy aging. Multiple anti-aging manipulations, such as senolytics, have proven beneficial for health; however, the biomarkers that label in vivo senescence at systemic levels are lacking, thus hindering anti-aging applications. In this study, we generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter allele at the Glb1 gene locus, which encodes lysosomal β-galactosidase—an enzyme elevated in tissues of old mice. A linear correlation between GAC signal and chronological age is established in a cohort of middle-aged (9 to 13 months) Glb1+/m mice. The high GAC signal is closely associated with cardiac hypertrophy and a shortened lifespan. Moreover, the GAC signal is exponentially increased in pathological senescence induced by bleomycin in the lung. Senolytic dasatinib and quercetin (D + Q) reduce GAC signal in bleomycin treated mice. Thus, the Glb1-2A-mCherry reporter mice monitors systemic aging and function decline, predicts lifespan, and may facilitate the understanding of aging mechanisms and help in the development of anti-aging interventions.