A Cellular Senescence-Centric Integrated Approach to Understanding Organismal Aging

Abstract: Aging remains the fundamental cause of the increased rate of morbidity and mortality in the elderly. Despite continuing research, an integrative and holistic understanding of the molecular mechanisms and effects of aging is still elusive. This presents a major challenge in biogerontology, and therefore novel strategies aimed at integrating the multifaceted nature of aging for the identification and development of successful therapeutic targets are highly desirable. At present, cellular senescence, immunosenescence, and gut microbiota dysbiosis are key known modulators of aging. However, a cellular senescence-centric integrative view that relates to the seemingly distinct processes of immunosenescence and gut microbiota dysbiosis can be envisaged, which implies a more inclusive and targetable understanding of aging. The present manuscript discusses the emerging evidence and significance of cellular senescence vis-à-vis immunosenescence and gut microbiota dysbiosis in the development of potential anti-aging therapies. Underlying interconnections and mechanisms amongst these individual modulators have been deliberated to present a more coherent and tangible understanding of biological aging. It is emphasized that aging be studied within the integrative purview of these processes that may ultimately help devise a new inclusive and consolidated theory of aging with well-defined therapeutic targets.