Obesity and Aging Share Biological Pathways Linked to Longevity Risk
Obesity and aging may be biologically interconnected processes that contribute to accelerated functional decline and increased mortality risk, according to Dominik Thor, PhD, MSc, during his session, “Normal BMI and Body Weight: The Keys for Longevity,” presented at Music City SCALE 2026.
Exploring how excess adiposity influences hallmarks of aging and emphasizing the importance of metabolic health and functional capacity over body mass index (BMI) alone, Dr Thor presented data that overweight and obesity are consistently associated with higher all-cause mortality; however, the relationship between BMI and health outcomes varies by age and metabolic status.
Dr Thor reviewed the concept of metabolically healthy obesity (MHO), a phenotype characterized by obesity without abnormalities in glucose metabolism, lipid profiles, blood pressure, or systemic inflammation. While MHO may initially appear lower risk, he stated that many individuals transition to metabolically unhealthy obesity within 5 to 10 years. Long-term outcomes remain associated with increased cardiovascular disease and mortality.
He highlighted that “aging is a multifactorial process, not a singular one,” and noted that obesity and aging share multiple biologic mechanisms. These include telomere attrition, mitochondrial dysfunction, impaired nutrient sensing, altered proteostasis, cellular senescence, and chronic inflammation.
Dr Thor described obesity-related inflammation as contributing to “inflammaging,” a chronic pro-inflammatory state associated with tissue damage and organ dysfunction during aging. Excess nutrient exposure may also accelerate mitochondrial damage and dysregulate pathways involved in metabolism and cellular repair.
A 2025 study found that long-term obesity beginning in adolescence or childhood was associated with accelerated biologic aging in young adults. These findings support the concept that obesity may influence aging trajectories early in life.
Discussing the age-related differences in BMI interpretation, Dr Thor remarked that in younger adults, higher BMI consistently correlates with elevated mortality risk. In older adults, however, the relationship weakens, reflecting factors such as frailty, sarcopenia, and illness-related weight loss. This phenomenon has contributed to discussion of the so-called “obesity paradox.”
As a result, he argued that clinicians should prioritize muscle mass and functional health rather than relying exclusively on BMI. Recommendations included measuring waist circumference and waist-to-hip ratio, assessing metabolic markers, and incorporating grip strength and functional testing into routine evaluation.
Dr Thor concluded that clinicians should “prioritize preserving/building muscle and reducing visceral fat rather than weight alone.”
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Reference
Thor D. Normal BMI and body weight: the keys for longevity. Presented at: Music City SCALE Symposium; May 13–17, 2026; Nashville, TN.
