Targeting Cellular Senescence for Healthy Aging: Advances in Senolytics and Senomorphics

Cellular senescence is a fundamental characteristic of aging, marked by permanent cell cycle cessation and the release of pro-inflammatory mediators. Although senescence plays advantageous roles in tissue regeneration and tumor suppression, its accumulation leads to aging-related illnesses and functional deterioration.

This review examines the processes of cellular senescence, its effects on aging and age-related disorders, and emerging therapeutic strategies to modulate senescence for promoting healthy aging.

A thorough literature review was performed using peer-reviewed studies on cellular senescence, its molecular pathways, and therapeutic interventions. Emphasis was placed on senolytics, senomorphics, and lifestyle interventions that modulate senescence-associated pathways. Studies published in Scopus, Web of Science and PubMed between 2014-2025 were selected.

Recent discoveries underscore the dual function of cellular senescence in aging and pathology. The senescence-associated secretory phenotype (SASP) fosters chronic inflammation and tissue dysfunction, connecting senescence to age-related diseases including cardiovascular conditions, dementia, and metabolic disorders. Therapeutic strategies, including senolytics (drugs that specifically eradicate senescent cells) and senomorphics (compounds that suppress SASP without killing cells), show promise in preclinical and clinical studies. Notably, dosing interals (intermittent vs continuous) influence both therapeutic efficacy and adverse events such as thrombocytopenia. Additionally, the state and limitations of clinical validation of aging biomarkers (eg, p16^INK4a, β-galactosidase) remain major hurdles for translation. Lifestyle interventions such as calorie restriction and exercise have also been identified as natural modulators of senescence pathways.

Targeting cellular senescence offers a promising avenue for promoting healthy aging and mitigating age-linked diseases. Continued research into senescence-modulating interventions may lead to novel therapeutics designed to prolong healthspan and lifespan.