This paper addresses the current uncertainty surrounding the characterization of senescent cells, particularly in the aging immune system. There is worry that current markers may not accurately identify senescent immune cells, and that other problematic populations exist. Immune system aging is complex, with various harmful populations like exhausted T cells and overly active microglia. The focus should be on obtaining an accurate understanding rather than solely testing clearance methods of certain immune cell subsets.
In young, healthy individuals, damaged cells can undergo cellular senescence, limiting dysfunctional cell spread. Senescent cells release a senescence-associated secretory phenotype (SASP) that attracts immune cells for clearance. However, when immune cells become senescent, clearing other senescent cells becomes ineffective, contributing to age-related dysfunction in various organs.
While T cells in aging individuals may exhibit cellular senescence similar to other cell types, common markers like CD27 and CD28 loss or upregulated KLRG-1 do not accurately identify true senescent cells. Utilizing specific cellular senescence markers like p16 and p21 is crucial for accurate identification. Future studies should delve into the functional properties of senescent T cells at different differentiation stages, exploring whether earlier stage T cells can also become senescent and contribute to age-related diseases. These questions demand further investigation.