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

Author

Listed:
  • Jie Sun

    (Shenzhen University
    Shenzhen University
    Shenzhen Bay Laboratory)

  • Ming Wang

    (Shenzhen University
    Shenzhen University)

  • Yaqi Zhong

    (Shenzhen University)

  • Xuan Ma

    (Shenzhen University)

  • Shimin Sun

    (Shenzhen University)

  • Chenzhong Xu

    (Shenzhen University
    Shenzhen University)

  • Linyuan Peng

    (Shenzhen University)

  • Guo Li

    (Central South University)

  • Liting Zhang

    (Shenzhen University)

  • Zuojun Liu

    (Shenzhen University
    Shenzhen University)

  • Ding Ai

    (Tianjin Medical University)

  • Baohua Liu

    (Shenzhen University
    Shenzhen University
    Shenzhen Bay Laboratory)

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.

Suggested Citation

  • Jie Sun & Ming Wang & Yaqi Zhong & Xuan Ma & Shimin Sun & Chenzhong Xu & Linyuan Peng & Guo Li & Liting Zhang & Zuojun Liu & Ding Ai & Baohua Liu, 2022. "A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34801-9
    DOI: 10.1038/s41467-022-34801-9
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    References listed on IDEAS

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