Alum Esther Ugo, Izah Sylvester Chibueze, Uti Daniel Ejim, Ugwu Okechukwu Paul-Chima, Betiang Peter A, Basajja Mariam, Ejemot-Nwadiaro Regina Idu
Department of Research Publications, Kampala International University, Kampala, Uganda.
Department of Community Medicine, Faculty of Clinical Sciences, Bayelsa Medical University, Yenagoa, Bayelsa, Nigeria.
Drug Des Devel Ther. 2025 Sep 19;19:8489-8522. doi: 10.2147/DDDT.S543211. eCollection 2025.
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.
细胞衰老为衰老的基本特征，其标志为细胞周期永久性停滞以及促炎介质的释放。尽管衰老在组织再生和肿瘤抑制中发挥有益作用，但其积累会导致与衰老相关的疾病和功能衰退。
本综述探讨细胞衰老的过程、其对衰老及衰老相关疾病的影响，以及为促进健康衰老而调节衰老的新兴治疗策略。
使用关于细胞衰老、其分子途径和治疗干预的同行评审研究进行了全面的文献综述。重点关注调节衰老相关途径的衰老细胞溶解剂、衰老细胞形态调节剂和生活方式干预措施。选取了2014年至2025年间发表于Scopus、科学网和PubMed的研究。
最近的发现强调了细胞衰老在衰老和病理学中的双重作用。衰老相关分泌表型（SASP）促进慢性炎症和组织功能障碍，将衰老与包括心血管疾病、痴呆和代谢紊乱在内的衰老相关疾病联系起来。治疗策略，包括衰老细胞溶解剂（特异性清除衰老细胞的药物）和衰老细胞形态调节剂（抑制SASP而不杀死细胞的化合物），在临床前和临床研究中显示出前景。值得注意的是，给药间隔（间歇性与连续性）会影响治疗效果和诸如血小板减少等不良事件。此外，衰老生物标志物（如p16^INK4a、β-半乳糖苷酶）临床验证的现状和局限性仍然是转化的主要障碍。卡路里限制和运动等生活方式干预措施也已被确定为衰老途径的天然调节剂。
针对细胞衰老为促进健康衰老和减轻与年龄相关疾病提供了一条有前景的途径。对衰老调节干预措施的持续研究可能会带来旨在延长健康期和寿命的新型疗法。
