Is Obesity Accelerated Aging? A Physiologic Perspective-Is Obesity Accelerated Aging? A Physiologic Perspective

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Video Summary

The session examined how obesity and aging interact to alter adipose tissue and liver function.<br /><br />Annabelle Wang described age-related changes in fat-cell populations. In male mice, visceral fat expands during midlife through both adipocyte enlargement and the emergence of new adipocytes. Her lab identified an age-specific committed pre-adipocyte population with heightened capacity to proliferate and form fat cells; blocking LIF-receptor signaling reduced this activity and visceral fat expansion. In brown fat, aging increased inflammatory IL-1β signaling, which was linked to lower UCP1 expression and reduced thermogenic responsiveness. Blocking glucocorticoid-receptor signaling improved cold response in aged mice.<br /><br />Ko Du focused on liver-cell senescence in metabolic dysfunction-associated steatotic liver disease (MASLD). His team developed gene signatures to identify senescent and biologically aged hepatocytes. These cells accumulate as disease advances, lose normal metabolic functions, and release signals that promote inflammation, fibrosis, and senescence in neighboring liver cells. A candidate senolytic reduced senescent-cell burden and improved liver pathology in mice. The team also found evidence that aged, diseased hepatocytes experience ferroptotic stress; inhibiting ferroptosis reduced senescence, inflammation, and fibrosis in aged mice.<br /><br />Together, the talks highlighted cell-population changes and aging-related stress pathways as potential contributors to metabolic disease, while identifying possible targets for intervention.

Keywords

obesity

aging

adipose tissue

visceral fat

pre-adipocyte

brown fat

UCP1

MASLD

hepatocyte senescence

ferroptosis