Researchers at the RIKEN Center for Integrative Medical Sciences (IMS) have found several age-related changes in the lipid metabolism of mice, in various organs and both sexes. One of the changes they observed was the accumulation of certain lipids produced by gut bacteria throughout the body as the mice aged. They also identified a sex difference in the kidneys and identified a gene responsible for it. This research has the potential to improve our understanding of chronic age-related conditions such as Alzheimer’s disease, atherosclerosis, kidney disease, and cancer.The metabolism of mice was studied and researchers found that there were changes in the accumulation of certain lipids in the body as the mice aged. They also found a difference in the kidneys between male and female mice, and identified a gene responsible for this difference. The study, published in Nature Aging, has the potential to improve our understanding of chronic age-related conditions such as Alzheimer’s disease, atherosclerosis, kidney disease, and cancer.
Lipids, which are fats or oils, are important for storing energy in our bodies and have other functions as well. Additionally, they act as signaling molecules in various biological processes.Atoms and molecules are the building blocks of all matter, including living organisms. They are essential for various biological processes, such as metabolism and cell structure. However, as we age, our metabolism slows down, leading to difficulties in weight management. This slowdown in metabolism is particularly evident in the breakdown of biomolecules like lipids and sugars. Despite knowing this for more than five decades, the precise impact of changes in lipid metabolism on lifespan and overall health is still not fully understood. Hiroshi Tsugawa and his team at RIKEN IMS conducted a recent study to address this gap in knowledge. They believe that before we can comprehend the effects of lipid metabolism on aging, we must first understand the specific changes that occur in great detail. By doing so, we can then begin to uncover potential connections between aging and lipid metabolism.Researchers used mice to create an atlas of age-related changes in lipid metabolites to better understand lipid metabolism and human health. Using a state-of-the-art technique to capture multiple snapshots of the mouse lipidome, which includes all lipid metabolites present in a biological sample, the researchers discovered an increase in BMP type lipids with age in the kidneys, liver, lungs, muscles, spleen, and small intestine of the mice. These lipids are important for cholesterol transport and breaking down biomolecules within cellular recycling centers called lysosomes. The researchers believe that age-related lysosomal damage may cause cells to produce more BMPs, which could have negative effects.The researchers looked into how gut bacteria can affect the lipidome, which is responsible for metabolic changes like increasing cholesterol derivatives in the kidney. They found that while gut bacteria produced many unique lipids, only sulfonolipids increased with age in the liver, kidney, and spleen. Other lipid metabolites from gut bacteria were not detected in these peripheral tissues. The next phase of research will involve testing the structure and physiological effects of the gut bacteria-derived sulfonolipids because this type of lipid is known to regulate immune responses.functions,” says Tsugawa.
The scientists also discovered that as mice age, there are differences in lipid levels based on sex, particularly in the kidneys. In older male mice, the lipid metabolite galactosylceramide was found in higher levels than in older females. This difference was linked to an increased expression of the UGT8 gene in male mice. Understanding these sex-specific metabolic differences could provide insight into susceptibility to age-related diseases in humans.
“Our research has thoroughly examined the changes in the lipidome that occur as mice age. In doing so, we have created a comprehensive guide that will be useful as a reference for future studies.””Increasing our understanding of the lipidome in mice is a crucial step in understanding aging,” explains Tsugawa. “We should also expand this research to study the human lipidome and microbiome.” These findings emphasize the significance of comprehending how lipid metabolism changes as we grow older, and the potential for targeting the lipidome in the development of treatments for age-related diseases.
