NK Cell-Mediated Clearance of Senescent Cells

A feature of physiological ageing is the accumulation of senescent cells. These cells, which have been detected in bone and skin samples obtained from older adults [90,91], reside in a state of irreversible cell cycle arrest, yet remain viable and meta- bolically active. Via their secretion of growth factors, pro-inflammatory cytokines, and proteases, senescent cells compromise tissue homeostasis and function, and their presence has been causally implicated in the development of such age- associated conditions as sarcopenia and cataracts [92].

Several studies have demonstrated a role for innate immune cells in the recognition and clearance of senescent cells [93, 94]. Of interest, via granule exocytosis, NK cells elicit potent cytotoxicity towards senescent cells [11]. As NK cells from older adults exhibit impaired perforin release upon target cell stimulation [33], NK cell immunosenescence may be one mechanism by which to explain the accumulation of senescent cells in aged tissue [11].

An emerging field of research in the area of senescence is the development of senolytics, a class of drugs aimed at selectively eliminating senescent cells. Recently, it was reported that a single-dose of senolytic drugs significantly reduced the number of senescent cells in multiple tissues of aged mice, resulting in amongst other things, improved functionality and the delayed onset of age-related symptoms and pathologies [95]. Whilst holding promise for combating the effects of ageing, seno- lytics will not reverse age-related changes in the immune system. Thus, should future studies prove that NK cells from older adults exhibit reduced cytotoxicity towards senescent cells, then an alternative to senolytics could be the therapeutic enhancement of NKCC, an approach that would restore the physiological route of senescent cell removal.

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