Molecular bases of adipose tissue aging

Aging impacts each and every living organism. In higher organisms, it is an asynchronous process with its onset and pace varying among tissue types as well as among different cell types within a tissue. Adipose tissue is the largest energy depot in the body and is an endocrine organ responsible for metabolic homeostasis. Adipose tissue aging is marked by fat redistribution, with increased visceral and reduced subcutaneous fat observed as we age. At molecular level, aging in adipose tissue is a multifaceted process driven by diverse mechanisms, involving dysregulated adipogenic pathways, impaired thermogenesis, reduced regeneration, onset of senescence, and emergence of inflammation. Dysregulated adipogenic pathways introduce metabolic dysfunction by compromising lipid metabolism, leading to complications such as insulin resistance and diabetes. In addition, beige and brown adipose tissue dysfunction further aggravates the scenario by impacting thermogenesis. Moreover, a decline in regenerative potential due to loss of function in APSCs limits adipogenesis. Onset of senescence within adipose tissue disrupts local tissue homeostasis by impairing cellular function and increasing metabolic stress. Chronic inflammation in adipose tissue extends its effects beyond local disruption, contributing to systemic metabolic imbalances. Here, we discuss our current understanding of molecular mechanisms driving adipose tissue aging, highlighting their implications in metabolic health. Interventions, such as, senolytics, pharmacological modulators, and adipose tissue-specific approaches offer promising avenues for mitigating aging-related dysfunction in adipose tissue. Identifying potential therapeutic targets and their clinical translation for preserving adipose function is crucial for mitigating the metabolic complications associated with aging.