Effects of varying levels and differing durations of calorie restriction on cellular and synaptic proteins, as well as the inflammatory state of the female mouse brain

Abstract

Aging is an inevitable and complicated process leading to functional decline. Regarding brain aging, cognitive decline takes place in multiple domains, including learning, memory, executive functions, motor coordination, and language. At the cellular and molecular level, age-related cognitive decline is elucidated with certain hallmarks, including aberrant neuronal network, stem cell exhaustion, glial cell activation, and inflammation. Calorie restriction (CR) is a widely-utilized approach for coping with aging’s detrimental effects even though there is no one agreed way for the application of CR. In this study, varying levels of CRs were applied for differing durations to MMTV-TGF-alpha female mice. The study initiated when mice were 10-weeks of age (Baseline) and carried out until 49/50 weeks of age and 81/82 weeks of age. There were four dietary groups named Adlibitum (AL; control), Chronic Calorie Restriction (CCR), Intermittent Calorie Restriction - Restriction (ICR-R), and Intermittent Calorie Restriction -Refeed (ICR-RF). The study’s first aim was to show age-related changes in the cellular and synaptic proteins and the inflammatory state of the female mice’s brains. The second aim of the study is to demonstrate the effects of varying levels of CR implemented for the short-term and the long-term manner on the same hallmarks. Our findings showed both chronic- or intermittent- CR altered the synaptic integrity proteins against brain aging at the long-term period (81/82 weeks) compared to the short-term (49/50 weeks) period except for PSD-95. Similarly, both chronic- or intermittent- CR showed an attenuative impact on the pro-inflammatory markers, but IL-6 was affected only by CCR at the same periods. Furthermore, an age-related imbalance between neurogenesis and astrogliogenesis was shown based on DCX and GFAP. Both chronic- or intermittent- CR showed a compensatory effect on it acting through astrogliogenesis, even though it was not statistically significant.