MTORC1 signaling pathway changes under the effect of caloric restriction in the hippocampus of male Wistar rats

Abstract

Caloric restriction (CR) is widely known for delaying age-related changes, but its duration and onset can significantly alter its protective potential. One of the underlying mechanisms of the effect of CR on aging is considered to be mTOR pathway, an important player in nutrient sensing and regulation of cellular metabolism. Adult, middle-aged, and old male Wistar rats were exposed to CR (60% of AL) to study the effect of CR of early (EOCR) and late onset (LOCR). Ad libitum (AL) fed animals were used to test the effects of aging and as age-matched controls for the effect of CR. Western blot was used to analyze the expression of proteins involved in the signaling cascade of mTOR complex 1 (mTORC1) in rat hippocampus. At 18 months of age, EOCR led to a decrease in phosphorylation of mTOR S2448, whereas LOCR led to its increase at 24 months of age. pAkt T308 was decreased with LOCR at 18 months, while at 24 months EOCR and LOCR increased its phosphorylation. LOCR also led to an increased phosphorylation of p70S6K1 at 24 months of age. Although EOCR led to a decrease in phosphorylation of mTOR at 18 months of age, this effect was lost at 24 months, and was also not affecting the activation of the two kinases targeting mTOR S2448. Negative effect of short-term LOCR at 24 months was consistent in all examined proteins suggesting a caution when implementing CR later in life.