Abstract
Caloric restriction (CR) can attenuate the general loss of health observed during aging, being one of the mechanisms involved the reduction of hormonal alteration, such as insulin and leptin. This change could also prevent age-specific fluctuations in brain monoamines, although few studies have addressed the effects of CR on peripheral hormones and central neurotransmitters exhaustively. Therefore, the variations in brain monoamine levels and some peripheral hormones were assessed here in adult 4-month old and 24-month old male Wistar rats fed ad libitum (AL) or maintained on a 30% CR diet from four months of age. Noradrenaline (NA), dopamine (DA), serotonin (5-HT) and its metabolites were measured by high-performance liquid chromatography with electrochemical detection (HPLC-ED) in nine brain regions: cerebellum, pons, midbrain, hypothalamus, thalamus, hippocampus, striatum, frontal cortex, and occipital cortex. In addition, the blood plasma levels of hormones like corticosterone, insulin and leptin were also evaluated, as were insulin-like growth factor 1 and other basal metabolic parameters using enzyme-linked immunosorbent assays (ELISAs): cholesterol, glucose, triglycerides, albumin, low-density lipoprotein, calcium and high-density lipoprotein (HDLc). CR was seen to increase the NA levels that are altered by aging in specific brain regions like the striatum, thalamus, cerebellum and hypothalamus, and the DA levels in the striatum, as well as modifying the 5-HT levels in the striatum, hypothalamus, pons and hippocampus. Moreover, the insulin, leptin, calcium and HDLc levels in the blood were restored in old animals maintained on a CR diet. These results suggest that a dietary intervention like CR may have beneficial health effects, recovering some negative effects on peripheral hormones, metabolic parameters and brain monoamine concentrations.
Highlights
Caloric restriction (CR) can attenuate the general loss of health observed during aging, being one of the mechanisms involved the reduction of hormonal alteration, such as insulin and leptin
The concentration of neurotransmitters and their metabolites was assessed in each brain region and in general, the concentration of monoamines differed between old CR and ad libitum (AL) animals
In this study, maintaining a CR diet from 4-months of age ameliorated the decline in monoamines in specific brain areas, as well as the increase in plasma leptin and insulin associated with aging
Summary
Caloric restriction (CR) can attenuate the general loss of health observed during aging, being one of the mechanisms involved the reduction of hormonal alteration, such as insulin and leptin This change could prevent age-specific fluctuations in brain monoamines, few studies have addressed the effects of CR on peripheral hormones and central neurotransmitters exhaustively. The insulin, leptin, calcium and HDLc levels in the blood were restored in old animals maintained on a CR diet These results suggest that a dietary intervention like CR may have beneficial health effects, recovering some negative effects on peripheral hormones, metabolic parameters and brain monoamine concentrations. Age-related impairment of brain function is associated with other physiological changes, including alterations of peripheral hormones like insulin14, leptin[15] and insulin-likegrowth factor 1 (IGF-1)[16], as well as increased levels of stress hormones like c orticosterone[17]. Despite the relationship between CR, monoamines and peripheral hormones, no studies have yet combined and correlated these elements, analyzing their relationships in different brain areas
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