Age-Related Changes In Lipid Metabolism

Lipids are essential for storing energy in our bodies, and among other jobs, they act as signaling molecules and as components of cell membranes. Metabolism slows down with age, which can lead to weight gain, and makes it more difficult to lose weight as we get older. This has been known for over five decades, however, how changes in lipid metabolism affect health and lifespan remains more unclear. This study set out to find what these actual changes were before looking for links between aging lipid metabolism and human health.

Using cutting-edge technology, the researchers took multiple snapshots of the rodent’s lipidomes and found that BMP-type lipids increased with age within the liver, lungs, spleen, muscles, small intestine, and kidneys of the animals. These lipids have important roles in cholesterol transport and the breakdown of biomolecules within lysosome cellular recycling centers. According to the researchers, age-related lysosomal damage could result in cells producing more BMPs leading to further metabolic changes like increasing cholesterol derivative in the kidneys. 

When investigating the impact of gut bacteria on the lipidome the researchers discovered that the gut bacteria produced many structurally unique lipids, but only sulfonolipids increased with age in the spleen, kidneys, and liver. Surprisingly, no other group of lipid metabolites from the gut bacteria was detected in these peripheral tissues at all. 

"As this kind of lipid is known to be involved in regulating immune responses, the next phase of our research will involve testing the gut bacteria-derived sulfonolipids to determine their structure and physiological functions," says Tsugawa.

Age-related sex differences were also found in the mouse lipidome, particularly within the kidneys, with levels of galactosylceramide lipid metabolites being more elevated in older male mice compared to older female mice. The difference was attributed to increased expression of the UGT8 gene which is only present in male mice. 

Discovering sex-specific metabolic differences such as this could offer insight into the susceptibility to age-related human diseases and may lead to a better understanding of chronic age-related conditions. This work highlights the importance of understanding how lipid metabolism changes as we age and points to the potential of targeting the lipidome when designing treatments for age-related diseases.

"Our research has comprehensively characterized the changes in the lipidome that occur in the mouse with aging. In doing so, we have created at atlas that will serve as an important global resource," says Tsugawa. "Next, we must extend this type of study to the human lipidome and microbiome."