Pathophysiological implications of cellular senescence and prospects for novel anti-aging drugs / 生理学报

ABSTRACT

Chronological aging is the leading risk factor for human diseases, while aging at the cellular level, namely cellular senescence, is the fundamental driving force of organismal aging. The impact of cellular senescence on various life processes, including normal physiology, organismal aging and the progress of various age-related pathologies, has been largely ignored for a long time. However, with recent advancement in relevant fields, cellular senescence has become the core of aging biology and geriatric medicine. Although senescent cells play important roles in physiological processes including tissue repair, wound healing, and embryonic development, they can also contribute to tissue dysfunction, organ degeneration and various pathological conditions during adulthood. Senescent cells exert paracrine effects on neighboring cells in tissue microenvironments by developing a senescence-associated secretory phenotype, thus maintaining long-term and active intercellular communications that ultimately results in multiple pathophysiological effects. This is regarded as one of the most important discoveries in life science of this century. Notably, selective elimination of senescent cells through inducing their apoptosis or specifically inhibiting the senescence-associated secretory phenotype has shown remarkable potential in preclinical and clinical interventions of aging and age-related diseases. This reinforces the belief that senescent cells are the key drug target to alleviate various aging syndromes. However, senescent cells exhibit heterogeneity in terms of form, function and tissue distribution, and even differ among species, which presents a challenge for the translation of significant research achievements to clinical practice in future. This article reviews and discusses the characteristics of senescent cells, current targeting strategies and future trends, providing useful and valuable references for the rapidly blooming aging biology and geriatric medicine.