The researchers RIKEN Center for Integrative Medical Sciences (IMS) report that they found numerous changes in lipid metabolism in mice across organs and genders. Natural aging The cause was the selective accumulation throughout the body of certain lipids produced by intestinal bacteria with age, as well as sex differences in the kidneys and the genes that cause them.
Lipids are essential for energy storage in the body and also serve as signaling molecules and components of cell membranes. Metabolism slows with age, which can lead to weight gain and makes weight loss more difficult as we age. This has been known for over 50 years, but it is still unclear how changes in lipid metabolism affect health and lifespan. In this study, we aimed to determine what these changes actually are, before exploring the link between lipid metabolism in aging and human health.
Using cutting-edge technology, the researchers took multiple snapshots of lipid membranes in rodents and found that BMP-type lipids increased with age in the animals’ liver, lungs, spleen, muscles, small intestine, and kidneys. These lipids play a key role in cholesterol transport and the breakdown of biomolecules in the lysosomal cellular recycling center. According to the researchers, age-related damage to lysosomes may cause cells to produce more BMPs, leading to further metabolic changes, such as an increase in cholesterol derivatives in the kidneys.
When investigating the effects of gut bacteria on lipid membranes, the researchers found that although gut bacteria produce many structurally unique lipids, only sulfonolipids increased with age in the spleen, kidney and liver. Surprisingly, other groups of gut bacterial-derived lipid metabolites were never detected in these peripheral tissues.
“Because this type of lipid is known to be involved in regulating immune responses, the next step in our research will be to examine sulfonolipids derived from gut bacteria to investigate their structures and physiological functions,” Tsugawa says.
Age-related sex differences in lipid composition, especially in the kidney, were observed in mice, with aged male mice exhibiting higher levels of the lipid metabolite galactosylceramide than aged female mice, and this difference was due to increased expression of the UGT8 gene, which is only present in male mice.
Uncovering such sex-specific metabolic differences may provide insight into susceptibility to age-related human diseases and improve our understanding of chronic age-related conditions. This study highlights the importance of understanding how lipid metabolism changes with age and demonstrates the potential for targeting lipids when designing therapies for age-related diseases.
“Our study has comprehensively revealed the changes in lipid composition that occur with age in mice, creating an atlas that will be an important global resource,” Tsugawa says. “Next, this type of research must be extended to human lipid composition and microbiomes.”
