Enhancing adipose tissue functionality in obesity: senotherapeutics, autophagy and cellular senescence as a target

• Published in: Biological research Vol. 57; no. 1; pp. 51 - 12
• Main Authors: Arias, Consuelo, Álvarez-Indo, Javiera, Cifuentes, Mariana, Morselli, Eugenia, Kerr, Bredford, Burgos, Patricia V
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.08.2024; BioMed Central; BMC
• Subjects: Adipocytes; Adipose Tissue; Adipose tissues; Aging; Animals; Autophagy; Autophagy - drug effects; Autophagy - physiology; Body fat; Cardiovascular disease; Cell cycle; Cell differentiation; Cellular Senescence - drug effects; Cellular Senescence - physiology; Chronic diseases; Chronic illnesses; Cytokines; Development and progression; Diabetes; DNA damage; Economic growth; Energy storage; Fatty acids; GDP; Genes; Gross Domestic Product; Homeostasis; Humans; Hyperplasia; Hypoxia; Inflammation; Insulin; Kinases; Metabolic disorders; Obesity; Obesity - drug therapy; Oxidative stress; Phenotypes; Physiology; Prevention; Proteins; Public health; Quality of life; Senescence; Senotherapeutics - pharmacology; Triglycerides; Type 2 diabetes; World health
• ISSN: 0717-6287; 0716-9760; 0717-6287
• DOI: 10.1186/s40659-024-00531-z

Obesity, a global health crisis, disrupts multiple systemic processes, contributing to a cascade of metabolic dysfunctions by promoting the pathological expansion of visceral adipose tissue (VAT). This expansion is characterized by impaired differentiation of pre-adipocytes and an increase in senescent cells, leading to a pro-inflammatory state and exacerbated oxidative stress. Particularly, the senescence-associated secretory phenotype (SASP) and adipose tissue hypoxia further impair cellular function, promoting chronic disease development. This review delves into the potential of autophagy modulation and the therapeutic application of senolytics and senomorphics as novel strategies to mitigate adipose tissue senescence. By exploring the intricate mechanisms underlying adipocyte dysfunction and the emerging role of natural compounds in senescence modulation, we underscore the promising horizon of senotherapeutics in restoring adipose health. This approach not only offers a pathway to combat the metabolic complications of obesity, but also opens new avenues for enhancing life quality and managing the global burden of obesity-related conditions. Our analysis aims to bridge the gap between current scientific progress and clinical application, offering new perspectives on preventing and treating obesity-induced adipose dysfunction.