Study Protocol Published for GendAge Trial to Investigate Age- and Sex-Dependent Responses to Caloric Restriction

The newly published GendAge Weight Loss Study protocol details a controlled feeding trial designed to investigate whether age, sex, and hormone replacement therapy status dictate physiological and metabolic responses to caloric restriction.

Researchers from the University of Aberdeen and the University of Edinburgh published the protocol for the GendAge Weight Loss Study in the journal Nutrition Bulletin.

The controlled feeding study will evaluate 75 younger and older men and women to determine if the metabolic effects of calorie restriction (CR) on fat mass, energy expenditure, and glucose homeostasis are dependent on age and sex.

The study aims to investigate whether estrogen acts as a modulator of the response to CR, building on preliminary animal and human data indicating that younger females are more resistant to CR-induced fat loss and reductions in energy expenditure than males, a resistance that diminishes in post-menopausal cohorts.

Additionally, the protocol outlines plans to test whether hormone replacement therapy (HRT) use in post-menopausal women restores a CR response profile similar to that observed in younger females.

Energy expenditure and body composition will be evaluated using gold-standard techniques, including doubly labelled water, paired with blood and abdominal adipose tissue sampling to analyze underlying endocrine mechanisms.

Existing dietary and weight management guidelines typically fail to account for sex or age, despite clear lifespan-related physiological differences in metabolic health between men and women.

Identifying the role of sex hormones in CR resistance or sensitivity could establish a biological foundation for personalized dietary interventions, directly supporting clinical approaches to healthy aging and obesity management.

By utilizing robust techniques like doubly labelled water and adipose tissue biopsies, the study aims to move past observational correlations to map precise hormonal and metabolic pathways.

The findings may guide stratification strategies in clinical trials for metabolic and anti-obesity therapeutics, showing developers how to control for hormonal and age-related variables that impact metabolic rate.

Better understanding of the intersection of reproductive aging and metabolic health supports the therapeutic rationale for targeting metabolic signaling pathways in specific age and gender cohorts.

The completion of the GendAge controlled dietary intervention trial in the 75-participant cohort and the subsequent publication of findings detailing the physiological and hormonal data.