The associations between biological markers of aging and appetite loss across adulthood: retrospective case-control data from the INSPIRE-T study.

Appetite loss is a common clinical condition in older adulthood, but how this condition associates with biological aging remains unknown. The present study aims to examine the associations of biological aging markers with appetite loss in community-dwelling people aged 21 to 102 years. This retrospective case-control study used baseline data from the INSPIRE-T cohort in Toulouse, France. Each of the 49 cases with appetite loss was sex- and age-matched to two controls without appetite loss (n = 147; median age of 79 years, interquartile range: 19.5; 67% women). Appetite loss was assessed using a single yes-no question from the World Health Organization´s Integrated Care for Older People screening tool. Biomarkers (first- and second-generation DNA methylation-based epigenetic clocks [Horvath, Hannum, PhenoAge, and GrimAge], the inflammatory aging clock iAge, and Adenosine triphosphatase inhibitory factor 1-IF1) were derived from blood samples. Logistic regression analyzed the associations of these markers with appetite loss. In fully adjusted models, accelerated aging using GrimAge was the only biomarker associated with appetite loss (Odds Ratio = 1.21, 95% Confidence Interval: 1.03, 1.43). When stratified by age (≤ 65 years vs. > 65 years) and sex, this association remained significant only in individuals over 65 years and men. Future research is needed to explore the potential mechanisms involved, as well as how other biological drivers of aging (e.g., cell senescence, deregulated nutrient sensing) relate to appetite loss.