Project description:We performed a factorial experiment examining the effects of calorie restriction (CR) and exercise (EX) in mice. CR mice received 70% of calories but 100% of all other nutrients compared to AL mice. Food consumption, weight gain, and physical activity levels were recorded for 6 weeks. Diet and exercise treatments, both alone and in combination, had significant effects on body composition and levels of physical activity. Affymetrix oligo microarrays were used to determine global gene expression patterns in mammary gland total RNA. CR and EX had some overlapping but primarily unique effects on mammary gene expression, with CR affecting a much larger number of genes. The gene changes presented suggest that CR and EX influence mammary gland development and potentially carcinogenesis through distinct pathways. Keywords: 2 X 2 factorial mouse experiment; ad lib; calorie restriction; exercise; exercise + calorie restriction. Endpoints: body composition; bone density; gene expression in mammary gland
Project description:Advanced age is one of the most recognizable risk factors for dry eye. Dry eye disease affects millions worldwide and can result from age-related lacrimal gland dysfunction, which correlates with a decline in lacrimal gland secretory cell function and chronic inflammation. This study investigated the potential of calorie restriction to maintain LG and ocular surface health. Adult female C57BL/6J mice were subjected to a 40% calorie restriction for four months, starting at 6–7 months and continuing until 10–11 months. These mice were compared to controls fed ad libitum. Bulk RNA sequencing of lacrimal glands, conjunctiva and cornea subjected to calorie restriction compared to ad libitum revealed significant differentially expressed genes (DEGs). Pathways enriched in the upregulated DEGs indicate enhanced circadian rhythm, secretory functions and lipid metabolism. These findings were confirmed using individual qPCR reactions and western blotting. In contrast, pathways enriched in the downregulated DEGs were associated with immune cell activation, adaptive immune responses, extracellular matrix remodeling, and metalloproteinase activity. Histological sections of calorie-restricted lacrimal glands revealed reduced mononuclear cell infiltration and fewer positive cells for CD4, CD19, and MHC II compared to libitum lacrimal glands. Calorie restriction also prevented age-related corneal barrier dysfunction and mitigated age-related conjunctival goblet cell loss, hallmarks of dry eye disease. These findings suggest that calorie restriction supports lacrimal gland and ocular surface health by reducing inflammation and extracellular matrix remodeling and by enhancing the lacrimal glands secretory function.
Project description:Calorie restriction (CR) extends lifespan by modulating the mechanisms involved in aging. We quantified the hepatic proteome of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated which signaling pathways were most affected.
Project description:Calorie restriction (CR) enhances stem cell self-renewal in various tissues, including the mammary gland. The hypothesis propelling this study states that similarly to their intestinal counterparts, mammary epithelial stem cells are insulated from sensing changes in the energy supply and, for that matter, depend on signals from a specific niche. Combined in vivo, in vitro and in silico studies identified macrophages and secreted CSF1 as the energy sensor and paracrine transmitter, respectively, of the CR inducing effect on mammary stem cell self-renewal.