Esther Ugo Alum, Sylvester Chibueze Izah, Daniel Ejim Uti, Okechukwu Paul-Chima Ugwu, Peter A Betiang, Mariam Basajja, Regina Idu Ejemot-Nwadiaro
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Although senescence plays advantageous roles in tissue regeneration and tumor suppression, its accumulation leads to aging-related illnesses and functional deterioration.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Targeting cellular senescence offers a promising avenue for promoting healthy aging and mitigating age-linked diseases. 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引用次数: 0
摘要
背景：细胞衰老是衰老的一个基本特征，其标志是细胞周期的永久停止和促炎介质的释放。虽然衰老在组织再生和肿瘤抑制中发挥着有利的作用，但它的积累会导致衰老相关疾病和功能退化。目的：本文综述了细胞衰老的过程，其对衰老和年龄相关疾病的影响，以及调节衰老以促进健康衰老的新治疗策略。方法：通过对细胞衰老、其分子途径和治疗干预的同行评议研究进行全面的文献综述。重点放在衰老学，同形学和生活方式干预，调节衰老相关的途径。选取2014-2025年间在Scopus、Web of Science和PubMed上发表的研究。结果：最近的发现强调了细胞衰老在衰老和病理中的双重功能。衰老相关分泌表型（SASP）促进慢性炎症和组织功能障碍，将衰老与年龄相关疾病联系起来，包括心血管疾病、痴呆和代谢紊乱。治疗策略，包括抗衰老药物（专门根除衰老细胞的药物）和senomorphics（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希望。值得注意的是，给药间隔（间歇或连续）影响治疗效果和不良事件，如血小板减少症。此外，衰老生物标志物（如p16^INK4a， β-半乳糖苷酶）的临床验证的状态和局限性仍然是翻译的主要障碍。生活方式干预，如卡路里限制和运动也被确定为衰老途径的天然调节剂。结论：靶向细胞衰老为促进健康衰老和减轻年龄相关疾病提供了一条有希望的途径。对衰老调节干预的持续研究可能会带来新的治疗方法，旨在延长健康寿命和寿命。
Targeting Cellular Senescence for Healthy Aging: Advances in Senolytics and Senomorphics.
Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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