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

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

  • Nat Commun. 2022 Nov 17;13(1):7028. doi: 10.1038/s41467-022-34801-9.
Jie Sun # 1 2 3,  Ming Wang # 1 2,  Yaqi Zhong # 1,  Xuan Ma 1,  Shimin Sun 1,  Chenzhong Xu 1 2,  Linyuan Peng 1,  Guo Li 4,  Liting Zhang 1,  Zuojun Liu 1 2,  Ding Ai 5,  Baohua Liu 6 7 8
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory for Systemic Aging and Intervention (SKL-SAI), School of Basic Medical Sciences, Shenzhen University, Shenzhen, 518055, China.
  • 2 Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, National Engineering Research Center for Biotechnology (Shenzhen), International Cancer Center, Shenzhen University, Shenzhen, 518055, China.
  • 3 Shenzhen Bay Laboratory, Shenzhen, China.
  • 4 Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  • 5 Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
  • 6 Shenzhen Key Laboratory for Systemic Aging and Intervention (SKL-SAI), School of Basic Medical Sciences, Shenzhen University, Shenzhen, 518055, China. ppliew@szu.edu.cn.
  • 7 Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, National Engineering Research Center for Biotechnology (Shenzhen), International Cancer Center, Shenzhen University, Shenzhen, 518055, China. ppliew@szu.edu.cn.
  • 8 Shenzhen Bay Laboratory, Shenzhen, China. ppliew@szu.edu.cn.
  • # Contributed equally.
PMID: 36396643 DOI: 10.1038/s41467-022-34801-9
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.

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