Adiponectin and aging: Mechanistic insights, clinical paradox, and therapeutic horizons

Adiponectin is an adipose tissue-derived peptide hormone that exerts beneficial metabolic effects in many tissues throughout the body. It is most well-known for its ability to enhance insulin sensitivity and dampen chronic inflammation. The impact of age on adiponectin is controversial; levels of adiponectin in circulation in older individuals have been linked to both positive and negative effects. This review integrates genetic, mechanistic, and therapeutic perspectives on adiponectin in aging. Specific considerations that might explain the "adiponectin paradox" are described and discussed. We present potential future applications of adiponectin-based strategies to prevent age-related metabolic dysfunctions and lower the risk for age-related chronic conditions. • Adiponectin has been implicated in aging and the onset of age-related disease • Adiponectin resides at the interface of metabolism and inflammaging • Tissue-specific actions reveal complexity in Adiponectin’s restorative actions • Adiponectin signaling protects multiple tissues from age-associated decline • Adiponectin signaling agonists as therapeutics in metabolic and age-related disease