Senescent T Cells Cause Changes in Fat Tissue that are Harmful to Long-Term Health

There is a much greater awareness in the scientific community of the importance of cellular senescence to aging. Senescent cells are influential in the progression of many facets of aging and age-related disease, and a new industry is working to produce senolytic therapies to clear senescent cells from old tissues. Further, there is funding and interesting for investigations of the many specific ways in which senescent cells cause harm. The open access paper noted here is an example of this sort of research, which the inflammatory signaling of senescent T cells is implicated as a contributing cause of detrimental age-related changes in fat tissue metabolism.

It has become evident that adipose tissue plays an endocrine function, not merely an energy reservoir pool, and exerts a fundamental influence on metabolic regulation. Adipose tissue is classified as white adipose tissue (WAT) and brown adipose tissue (BAT). BAT has been considered a key for thermogenesis to maintaining body temperature, while WAT stores and releases lipids and is involved in promoting inflammation. BAT "whitening" refers to acquisition of white adipocyte characteristics with enlarged lipid droplets and loss of normal structure and function of brown adipocyte. Age-related alteration in adipose tissues is manifested on the distribution and composition, as well as a decline in adipose tissue quality and function.

Immune cells particularly T cells accumulate in adipose tissue with advancing age, and there exists a cross talk between T cell and preadipocyte, contributing to age-related adipose tissue remodeling. Here, we compared the difference in morphology and function of adipose tissue between young (3-month-old) and old (18-month-old) mice and showed the phenomenon of brown adipose tissue (BAT) "whitening" in old mice. Flow cytometry analysis suggested an increased proportion of T cells in BAT of old mice comparing with the young and exhibited senescent characteristics.

We take advantage of coculture system to demonstrate directly that senescent T cells inhibited brown adipocyte differentiation of preadipocytes in adipose tissue. Mechanistically, both in vitro and in vivo studies suggested that senescent T cells produced and released a higher level of IFN-γ, which plays a critical role in inhibition of preadipocyte-to-brown adipocyte differentiation. Taken together, the data indicate that senescent T cell-derived IFN-γ is a key regulator in brown adipocyte differentiation.

Link: https://doi.org/10.3389/fcell.2021.637424

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