Making Senescent Cells Glow In Vivo

Currently there is some debate over whether the initial markers used to detect senescent cells, such as as senescence-associated β-galactosidase and P16 expression, are general enough across cell types and specific enough to senescent cells for all uses in research and clinical development. Nonetheless, these markers are well known and the efficiency of senolytic treatments that clear senescent cells does appear to be measurable this way. Greater convenience in that measurement is always useful: at present, the state of the art involves biopsies and post-mortem tissue histology. Here researchers take a step forward by producing a mouse lineage in which senescence-associated β-galactosidase expression is associated with fluorescence, allowing for more cost-effective investigation of cellular senescence and its treatment.

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.

Link: https://doi.org/10.1038/s41467-022-34801-9

Comments

Hello everybody.
Today is 20 years exactly of the first post on this website.

https://www.fightaging.org/archives/2002/11/ Posted on 29 November 2002.

Can we say to Reason big "thank you" for his enormous, professional, non-stopping, patient job to fight aging please?

Kind regards
Let's live longer to live forever.

Alek Ales (Alexei)

Posted by: Alek Ales at November 29th, 2022 3:03 PM

AGREED! Thank you Reason for your all of your work in fighting aging. From your thoughtful comprehensive reviews of the latest longevity research innovations; to your proactive work in developing longevity therapeutics; to making connections across disciplines, backgrounds and geography; you have really helped advance the entire field.

Posted by: Edward F Greenberg at December 8th, 2022 2:59 PM
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