Fats influence the speed of aging

Researchers at DZNE discovered that certain fatty substances are related to how fast humans are aging. To do so, they used a new high-tech examination method - and samples from the "Rhineland Study".

How old people get depends not least on lipids: These fat-like components of cells can transmit signals between cells - with far-reaching consequences. Researchers from DZNE and the University of Bonn recently found out in a large-scale investigation which lipids accelerate biological aging and which lipids slow it down. They published their results in the renowned scientific journal "Aging Cell". "Worldwide, life expectancy is steadily increasing," says Dr. Dan Liu, the publication’s lead author. "Our investigation can be a first step to promote healthy aging." For their research, the Bonn-based experts used blood samples from more than 4,000 participants of the Rhineland Study. "Our study, which is one of the most innovative population studies worldwide, thus demonstrates once again how valuable its data are for health research," says Prof. Monique Breteler, who heads the Rhineland Study at DZNE.

Lipids is a generic term for a large group of fat-like substances. Lipids play an important role in signal transmission between cells - and thus also in aging processes. In their study, Dan Liu and her colleagues have now for the first time examined more than 1,000 different fat molecules, from a total of 14 different classes, and broken down in detail which of the numerous lipids have an effect on aging. With this knowledge, new approaches can now be developed to better understand aging processes and perhaps even slow them down.

The study arose from an interesting observation: "It has been known for a long time that people age at different speeds. Two people can be the same age, but their age condition - the so-called biological age - can be different," says epidemiologist Dan Liu. While some people still appear almost youthful at an advanced age, they are healthy and can move without impairments, in others physical as well as mental abilities are quickly declining. Evidence that lipids play a role in this has existed for some time. The particular challenge for scientists lies in the quantity of different lipids, which all have to be examined individually. Dan Liu's team used blood samples from participants of the Rhineland study - and a new method in which state-of-the-art instruments screen each of these blood samples with unprecedented precision. Many hundreds of compounds were examined in the process - in all 4,181 study subjects. "So we had to work our way through massive data sets for the analysis, which alone was one of the hurdles in our work," Liu explains.

For each subject, the research team determined the biological age. They used epigenetic age estimation, the two most established methods of which are AgeAccelPheno and AgeAccelGrim. In these approaches, biological age is determined by analyzing DNA methylation. This is a change in DNA that does not alter the genetic information, but does affect gene expression, i.e. whether genes are “read” or not. Environmental influences - be it personal behavior such as diet and lifestyle, or the reaction to pollutants, for example - modify DNA methylation. Because DNA has a direct impact on physical processes, methylation can be used to draw conclusions about biological age.

The researchers now looked for a link between biological age and lipids. Their clear finding: Study participants with a high biological age, exhibited particularly high levels of certain lipids in their blood. Other lipids, in turn, were remarkably more frequent in those subjects who had aged more slowly.

"We were the first to combine such an in-depth analysis of blood samples with a very broad field of participants," the DZNE researchers say. This was only possible due to the large data base of the Rhineland Study, as the researchers made use of stored blood samples from study participants. "The design of the Rhineland Study is purposefully designed to collect biosamples and data as comprehensively and technologically advanced as possible, so that they can be used for numerous studies. That, along with its large sample size of currently more than 10,000 participants, makes this study unique," says Monique Breteler, the Rhineland Study's principal investigator.

One connection in particular caught the attention of the researchers: "The lipid profiles that we found to be associated with faster aging coincide with the lipid profiles that are also found in patients with neurodegenerative diseases such as Alzheimer's," says Dan Liu. So the particular lipids that are related to faster aging also appear to have an impact on neurodegeneration.

According to Dan Liu and her colleagues, a next step would be to test in model organisms how the faster aging processes actually take place. Thus, if the exposure to certain lipids changes, can this accelerate or slow down biological aging? And what role does nutrition play in this? The DZNE researchers are convinced that such a follow-up study could provide valuable information for strategies on how individuals can promote their health and also potentially lead to the development of new drugs that support healthy aging.

October 2023