Highlights in this article
The senescent cells are associated with aged-like inflamed microenvironment and increased risk of age-related organ disorders. However, the impact of senescent cells on the tissue repair process after injury was unclear. Dr. Muñoz Cánoves’s group in CNIC in Spain identified novel markers for senescent cells in vivo. Using this technique, scientists are able to isolate an enriched senescent population to study the functions of senescent cells in vivo. As senescent cells also emerge in damaged human muscle and disturbing tissue regeneration, these findings suggest that tissue regeneration including sarcopenia can be improved by eliminating senescent cells.
Background
Senescence is a process of cellular aging, which occurs naturally in all organisms. It is characterized by decreased growth, increased mortality, and increased risk for age-related diseases. During this process, cells become unable to divide, and instead accumulate damage that leads to a decrease in their function. Senescence is an important factor in the aging process, as it can cause cellular dysfunction, decreased tissue regeneration, and increased risk of age-related diseases. By contrast, it is also thought to play a role in tumor cell proliferation. In humans, senescence is associated with increased levels of inflammation and fibrosis, which can further impair tissue regeneration. Senescent cells are also found in the regenerative niche, and are thought to contribute to the decline in tissue regeneration that occurs with age. Understanding the molecular mechanisms of senescence is important for developing potential therapies to reduce its effects, and improve tissue regeneration.
Discovery
This study revealed that senescent cells are important components of the skeletal muscle regenerative niche, and their accumulation with age arrests tissue regeneration. They provide a technique for isolating in vivo senescent cells, define a senescence blueprint for muscle and uncover a non-productive function of senescent cells in regenerative niches that can be overcome. Their transcriptome, chromatin and pathway analyses using senescent cells revealed two universal senescence hallmarks (inflammation and fibrosis) across cell type, regeneration time and aging. They further demonstrated that reducing the burden of senescent cells, or reducing their inflammatory secretome, accelerates regeneration in both young and old mice. Their findings suggest that targeting senescent cells may be a promising strategy for improving muscle repair throughout life.
For more information:
Nature 2022 12/21
https://www.nature.com/articles/s41586-022-05535-x
Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration
Dr. Muñoz Cánoves’s website: