Emerging cellular senescence-centric understanding of immunological aging and its potential modulation through dietary bioactive components

Abstract

Immunological aging is strongly associated with the observable deleterious effects of human aging. Our understanding of the causes, effects, and therapeutics of aging immune cells has long been considered within the sole purview of immunosenescence. However, it is being progressively realized that immunosenescence may not be the only determinant of immunological aging. The cellular senescence-centric theory of aging proposes a more fundamental and specific role of immune cells in regulating senescent cell (SC) burden in aging tissues that has augmented the notion of senescence immunotherapy. Now, in addition, several emerging studies are suggesting that cellular senescence itself may be prevalent in aging immune cells, and that senescent immune cells exhibiting characteristic markers of cellular senescence, similar to non-leucocyte cells, could be among the key drivers of various facets of physiological aging. The present review integrates the current knowledge related to immunosenescence and cellular senescence in immune cells per se, and aims at providing a cohesive overview of these two phenomena and their significance in immunity and aging. We present evidence and rationalize that understanding the extent and impact of cellular senescence in immune cells vis-à-vis immunosenescence is necessary for truly comprehending the notion of an ‘aged immune cell’. In addition, we also discuss the emerging significance of dietary factors such as phytochemicals, probiotic bacteria, fatty acids, and micronutrients as possible modulators of immunosenescence and cellular senescence. Evidence and opportunities related to nutritional bioactive components and immunological aging have been deliberated to augment potential nutrition-oriented immunotherapy during aging.

Exploring the emerging bidirectional association between inflamm‐aging and cellular senescence in organismal aging and disease

“…Moreover, many of these supporting observations are largely based on preclinical assessments, and studies exclusively focused on understanding inflamm‐aging vis‐à‐vis cellular senescence are rare. Thus, clinical trials within the specific purview of inflamm‐aging and cellular senescence should be pursued. The already intricate relationship between immunosenescence and inflamm‐aging 140 is further complicated by the presence of cellular senescence in immune cells per se 141 . In this regard, it needs to be conclusively determined whether or not the subtle activation of cellular senescence manifests as SASP in senescent immune cells and that how it impacts the contribution of innate immune cells to inflamm‐aging (especially considering immune adaptation). SASP is a strong promoter of inflamm‐aging.…”

“…The already intricate relationship between immunosenescence and inflamm‐aging 140 is further complicated by the presence of cellular senescence in immune cells per se 141 . In this regard, it needs to be conclusively determined whether or not the subtle activation of cellular senescence manifests as SASP in senescent immune cells and that how it impacts the contribution of innate immune cells to inflamm‐aging (especially considering immune adaptation).…”