Cellular senescence is a fundamental biological phenomenon featuring an irreversible cell-cycle arrest coupled with persistent metabolic activity and the release of pro-inflammatory factors (collectively termed as the senescence-associated secretory phenotype or SASP). Although transient senescence performs important homeostatic roles, e.g., in the context of tissue repair, embryogenesis and tumor suppression, the accumulation of senescent cells during life ultimately promotes aging and is a major cause of an increasing number of age-associated chronic diseases. This review summarizes the molecular biology of cell senescence by discussing the roles of genomic instability, telomere shortening, oxidative stress, mitochondrial perturbation and p53/p21 and p16INK4a/RB signaling pathways in inducing senescence. It also reveals how senescent cells influence tissue homeostasis, immune regulation and chronic inflammation to promote cardiovascular disease, neurodegenerative diseases; cancer and other aging relate maladies. Moreover, cutting-edge senotherapeutic strategies such as senolytics, senomorphics, regenerative medicine and personalized therapy to improve healthspan and reduce the burden of age-related diseases life are examined. It focuses on emerging technologies, biomarker discovery and precision medicine that can further improve early diagnosis and therapeutic efficacy. Taken together, the dual physiological and pathophysiological nature of cellular senescence offers a solid foundation for novel anti-aging therapies to protect human health during aging.