A Glb1-2A mCherry reporter monitors and predicts lifespan of middle-aged mice
As CAD, AD and cancer demonstrate, aging increases the risk of developing disease. Understanding the mechanisms of aging will improve early diagnosis and may provide strategies to prevent and treat diseases. Biomarkers that are specific for in vitro mammalian cell culture senescence have been well defined, but those that are specific for in vivo systemic aging/senescence remain rare. We generated a Glb1+/m targeted allele at Glb1 that encodes b galactosidase. The GAC signals indicate Glb1 levels. The live-imaged GAC signals are linearly related to chronological age. However, this correlation is only seen in mice between 9-13 months of age. A high GAC level at the MA stage is associated with cardiac hypertrophy, and shorter lifespan. GAC was also exponentially elevated in BLM-induced pathological lung fibrous tissue. This in vivo mouse reporter can monitor systemic ageing and organ dysfunction in a way that is closely related to lifespan. It provides a system ideal for studying anti-aging mechanisms and developing antiaging manipulations.
Both the upregulation of SAb-gal staining and the elevated transcription of p16Ink4a are well-established biomarkers of cellular senescence17. The former has led to the development of live-imaging aged reporter mice20. It is interesting to note that a high level of p16Ink4a (as indicated by luciferase) predicts cancer rather than longevity. In vivo, SAb-gal is not widely used as a tissue senescence indicator. It is relatively easy to get positive SAb-gal staining in the kidney and adipose tissues, but more difficult in the blood vessels and heart. SAb-gal staining did not detect many positive cells in older individuals26. This raises the issue of whether SAbgal is a marker for in vivo cell senescence, or if in fact the percentage of in-vivo senescent cellular population is very low.
Source:
https://www.nature.com/articles/s41467-022-34801-9
