Unveiling Age-Related Lipid Alterations

Researchers from the RIKEN Center for Integrative Medical Sciences (IMS) revealed various age-related alterations in mice's lipid metabolism across both organs and sexes. As the mice grew older, they selectively accumulated specific lipids generated by gut bacteria throughout their bodies.

They also uncovered a sex difference in kidneys and the gene that causes it. This study, published in Nature Aging, might help researchers better understand chronic age-related conditions such as Alzheimer’s disease, atherosclerosis, renal disease, and cancer.

Lipids, which are commonly found in the form of fats or oils, are necessary components for the body to store energy, among other things. Furthermore, lipids function as signaling molecules and membrane components.

Metabolism, or the breakdown of biomolecules such as lipids and sugars into their constituent components, slows as we age, which helps explain why it is easier to acquire weight and more difficult to lose it.

Although this has been known for over 50 years, it is still unknown how alterations in lipid metabolism, in particular, impact longevity and health. Hiroshi Tsugawa and his team at RIKEN IMS reasoned in their latest study that understanding the real changes in great detail is important before properly answering this issue.

Only then can scientists begin to investigate connections between aging lipid metabolism and human health. To achieve this, scientists employed mice to create an atlas of age-related alterations in lipid metabolites.

Using a cutting-edge approach to obtain several snapshots of the mouse lipidome (all lipid metabolites present in a biological sample), the researchers discovered that BMP-type lipids increased with age in the mice’s kidneys, liver, lungs, muscles, spleen, and small intestine.

These lipids serve important functions in cholesterol transport and biomolecule breakdown in cellular recycling units known as lysosomes.

Age-related lysosomal damage may cause cells to produce more BMPs, which might lead to other metabolic alterations, such as an increase in cholesterol derivatives in the kidney.

The researchers also looked into the effect of gut bacteria on the lipidome and discovered that, while gut bacteria produced numerous structurally distinct lipids, only sulfonolipids increased with age in the liver, kidney, and spleen. In fact, no additional lipid compounds from gut bacteria were found in these peripheral tissues.

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.”

Hiroshi Tsugawa, Associate Professor, RIKEN Center for Integrative Medical Sciences

The researchers also discovered age-related sex variations in the mouse lipidome, notably in the kidneys. Older male mice had greater amounts of the lipid metabolite galactosylceramide than older females.

This disparity was attributable to greater expression of the UGT8 gene in male mice. Understanding sex-specific metabolic changes like these should help people better understand their vulnerability to age-related diseases.

Tsugawa stated, “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. Next, we must extend this type of study to the human lipidome and microbiome.”

The findings emphasize the significance of knowing how lipid metabolism varies with age and the possibility of targeting the lipidome when developing treatments for age-related diseases.