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

Jie Sun, Ming Wang, Yaqi Zhong, Xuan Ma, Shimin Sun, Chenzhong Xu, Linyuan Peng, Guo Li, Liting Zhang, Zuojun Liu, Ding Ai and Baohua Liu ()
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Jie Sun: Shenzhen University
Ming Wang: Shenzhen University
Yaqi Zhong: Shenzhen University
Xuan Ma: Shenzhen University
Shimin Sun: Shenzhen University
Chenzhong Xu: Shenzhen University
Linyuan Peng: Shenzhen University
Guo Li: Central South University
Liting Zhang: Shenzhen University
Zuojun Liu: Shenzhen University
Ding Ai: Tianjin Medical University
Baohua Liu: Shenzhen University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The 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.

Date: 2022
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DOI: 10.1038/s41467-022-34801-9

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