Physiological Approaches Targeting Cellular and Mitochondrial Pathways Underlying Adipose Organ Senescence

Abstract

The adipose organ is involved in many metabolic functions, ranging from the production of endocrine factors to the regulation of thermogenic processes. Aging is a natural process that affects the physiology of the adipose organ, leading to metabolic disorders, thus strongly impacting healthy aging. Cellular senescence modifies many functional aspects of adipose tissue, leading to metabolic alterations through defective adipogenesis, inflammation, and aberrant adipocytokine production, and in turn, it triggers systemic inflammation and senescence, as well as insulin resistance in metabolically active tissues, leading to premature declined physiological features. In the various aging fat depots, senescence involves a multiplicity of cell types, including mature adipocytes and immune, endothelial, and progenitor cells that are aging, highlighting their involvement in the loss of metabolic flexibility, one of the common features of aging-related metabolic disorders. Since mitochondrial stress represents a key trigger of cellular senescence, and senescence leads to the accumulation of abnormal mitochondria with impaired dynamics and hindered homeostasis, this review focuses on the beneficial potential of targeting mitochondria, so that strategies can be developed to manage adipose tissue senescence for the treatment of age-related metabolic disorders.

Oxidative Stress, Inflammation, and Mitochondrial Dysfunction: A Link between Obesity and Atrial Fibrillation

“…In the presence of mitochondrial dysfunction, there is a significant increase in the production of ROS, with consequences on mitochondrial and nuclear nucleic acids, membrane lipids and proteins, and the enzymes of the mitochondrial respiratory chain [124]. This entire process is significantly amplified by the aging of the adipose organ, which leads to alterations in adipogenesis, insulin resistance, abnormal adipokine secretion, inflammation, mitochondrial dysfunction, and cellular and tissue senescence [125,126].…”

Mitochondrial dynamics and metabolism across skin cells: implications for skin homeostasis and aging

“…Mitochondrial dysfunction in adipose tissue during aging is linked to cellular senescence, chronic inflammation, and decline in stem cell activity, as well as obesity and insulin resistance ( Woo et al, 2019 ; Ou et al, 2022 ). Senescent adipose progenitor cells display poor differentiation capacity associated with high expression levels of p53 and p16 INK4a , reduced insulin-dependent glucose transport, and hypertrophic expansion of adipocytes ( Krstic et al, 2018 ; de Lange et al, 2023 ).…”