Clinical studies planned to determine if metabolic biomarkers predictive of mortality can be used to identify people at risk for developing disease.
Germany’s Max Planck Institute for Biology of Aging is a renowned centre of excellence for its work in the study of how we age. One of its newest labs studies the genetic mechanisms underlying healthy aging in humans, as well as identifying and validating biomarkers of healthy aging.
Longevity.Technology: The lab’s leader is Dr Joris Deelen, the man behind the key 2019 study, which found a set of metabolic biomarkers that may help predict mortality. We caught up with him recently to find out more about his work in this area and beyond.
As much of the institute’s work focuses on animal models, Deelen’s lab was founded with the goal of doing more research in humans. His work in metabolomic biomarkers is the lab’s highest profile body of research conducted in recent years.
“We first looked at normal clinical markers that were already used in the clinic and looked how these could relate to longevity and healthy aging,” says Deelen. “For example, when you go to the clinic, you get your blood taken to check glucose, triglycerides and other standard things. But we found that these biomarkers are not optimal for information about healthy aging.”
Metabolomics and mortality
Deelen and his colleagues then started to shift their focus towards metabolomics, and joined forces with Finnish health tech company Nightingale Health, which offers a comprehensive metabolomic analysis platform. Together, they collaborated on a huge study of more than 40,000 people, looking at how certain metabolites influence mortality.
“We also wanted to know which biomarkers work independently from each other, and we ultimately came up with a with a set of 14 biomarkers that seem to be very predictive for mortality,” says Deelen, whose next step is to set up further clinical studies. “We want to see if we can actually use these biomarkers in the clinic to identify vulnerable people – not just people that are at risk of dying, but also at risk for developing diseases. And then, if we can identify those people, can we treat them preventatively?”
While the initial study only used mortality as its outcome, Deelen says that the biomarkers can also tell us a lot more about our health in general.
“It seems that if you have a bad profile of these biomarkers, you are potentially at risk for developing age-related diseases,” he explains. “So that’s why we want to go into the clinic, because we know that these markers are better than the current clinical markers, and we want to see if we can convince doctors and others to start using them.”
Clinical study planned
The forthcoming clinical study will be much smaller, probably including around 100 patients. The one-year study will also incorporate an interventional aspect, with input from specialists like dieticians and physiotherapists.
“It will be a more tailored intervention, not like a drug study, it will really be personal,” says Deelen. “We already know from other studies that there isn’t one intervention that fits everybody, but we need the intervention component, because we want to see how things change over time and if we can prevent some things from happening.”
Deelen is also interested to learn how his work in metabolic biomarkers compares with things like epigenetic clocks.
“Will epigenetics say something different, or will they all say the same things?” he wonders. “I suspect that the metabolome only provides part of the picture, and the epigenome another part. And when we combine them, and maybe also add proteome-based or other biomarkers, then we can get a more complete picture, and we get better in identifying the individuals at risk, because that’s our goal.”
The genetics of longevity
On the genetic side of his work, Deelen is keen to explore how specific genetic variations could potentially lead to longer lifespan.
“There are examples of specific families that are very long-lived, and we think there is a genetic component that explains it,” he says. “We’re now trying to use this genetic data to functionally characterise the variants that we identify – both in cell models and in model organisms.”
“So we identify this variant in this very old people, and I’m looking in the lab, how they influence the metabolic processes, in cells and in animals, and then hopefully, that will give us information about how it would also work in humans.”
Last year, Deelen published a paper on the genetics of aging, which identified 10 new variants, including five that had not been previously reported as having genome-wide significance.
“We decided to use the phenotypes of whether a person lives to an exceptional old age, the lifespan of a person’s parents, and a person’s disease-free lifespan, and then combine these three together to see which genetic variants are doing something with all three,” he says. “We identified several new variants, and we also identified that they are specifically targeting haem metabolism (blood iron).”
“After exploring this further, we found that it seems to be that if you have genetic variation that makes your blood iron high, you have increased risk of dying earlier, and of having a worse healthspan.”
Deelen’s next step is to learn how these genetic variations functionally work at the cellular level.
“The ideal situation would be that we would then find a shared mechanism or multiple mechanisms that are encoded in the genome of these long-lived people, so we can then target these mechanisms with specific kinds of drugs.”
