High calorie diet background alters the expression of sirtuins in the testes of mice under caloric restriction

Abstract Caloric restriction (CR) is considered one of the most efficient interventions that extend lifespan and healthspan by delaying the onset of many age-related diseases in a variety of organisms. CR appears to activate sirtuins, which in turn modulate a wide range of cellular activities related to pathophysiological conditions such as stress and inflammation, DNA repair, apoptosis, and the processes of aging. In this work we aimed to determine whether CR can counteract the detrimental effects of a high-calorie diet (HCD) on the mRNA and protein levels of sirtuins in testes of a murine experimental model. We report in here that short-term CR increased the mRNA and protein expression of all sirtuins in the animals previously feed standard food. However, short-term CR failed to activate sirtuins in the animals previously fed an HCD for a period of 4 months. Moreover, histologic analysis of adipocyte/lipid infiltration by oil red O assay, in the mice testis, showed that the highest lipid content was found in the animals with an HCD background, exposed to CR. Mechanistic actions, as well as substrates that modify sirtuins transcriptional and translational expression in the mice male reproductive system, are still not well understood. We believe that deeper insights into how the potential selective modulation of SIRT family members and sirtuins activators affect the different organs, individually and as a whole system will eventually led to the development of preventative and therapeutic strategies to promote health and longevity.