Natural killer cell-based senotherapy: a promising strategy for healthy aging

One of the most significant risk factors for diseases is aging. Interestingly, some organisms, such as naked mole-rats and most turtles, do not exhibit typical aging-like symptoms or increased mortality as they become older. These aspects indicate that aging is not necessarily an essential event for animal life and are avoidable. Overcoming aging would free humans from age-associated diseases (AADs) and prolong lifespans. Recent studies have demonstrated that one of the causes of age-related organ dysfunction is excessive chronic inflammation caused by the accumulation of senescent cells (SNCs) and their senescence-associated secretory phenotypes (SASPs). Therefore, the development of drugs and medication to remove SNCs is ongoing. Natural killer (NK) cells are integral components of the innate immune system that are critical for clearing SNCs. Beyond this direct function, NK cells also orchestrate innate and adaptive immunity responses to survey and eradicate these compromised cells. Consequently, preserving NK cell function throughout the aging process is paramount for mitigating AADs and promoting robust health in later life. Simultaneously, NK cell-based senotherapy presents compelling avenues for addressing the multifaceted challenges associated with SNC accumulation and aging. Recent investigations into adoptive NK cell-based senotherapy have demonstrated considerable promise in rejuvenating immunosenescence, facilitating SNC elimination. The accumulating evidence provides a promising proof-of-concept for adoptive NK cell-based senotherapy, indicating its potential as a development in longevity therapeutics.