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
  • 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. [email protected].
  • 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. [email protected].
  • 8. Shenzhen Bay Laboratory, Shenzhen, China. [email protected].
  • # 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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