Androgen receptor gene polymorphism and biological age markers in men

Abstract

Abstract Inter-individual differences in aging rates may stem from the trade-offs between reproductive effort and somatic maintenance, with higher reproductive effort potentially reducing healthspan and lifespan. In men, these trade-offs are thought to be regulated by androgens, where high androgen levels incur biological costs. However, the relationship between androgen levels, health, and aging is complex, and the role of androgen receptor (AR) sensitivity in aging remains unclear. Thus, this study aimed to investigate whether genetic polymorphisms in the AR gene, related to receptor affinity and androgen sensitivity, predict biological age in men. The analyses included 131 healthy men (mean age: 35.4, age range 30–45). Biological age was assessed using physiological markers, including klotho, inflammatory markers, oxidative stress, total antioxidant capacity, and DHEA/S levels. AR sensitivity was estimated based on CAG repeat length in exon 1 of the AR gene (AR CAGn), with shorter repeats indicating higher sensitivity. The independent effect of testosterone (T) level, as well as its potential interaction with AR CAGn, was also verified. Chronological age, body adiposity, lifestyle factors, and cortisol levels were controlled for. Results showed no relationship between AR CAGn and biological age markers, directly or through interaction with T levels. Findings suggest that lifetime testosterone fluctuations, influenced by environmental and health factors, may obscure the link between AR CAGn and reproductive/somatic investment, ultimately affecting the aging rate.