- A new study highlights that people with a biological age older than their chronological age have a higher risk of developing dementia and may develop the disease earlier in life.
- The findings suggest that individuals with both accelerated biological aging and genetic risk factors could be up to 10 times more likely to develop dementia.
- Using a blood-based ‘metabolomic aging clock’ could help identify those at risk before symptoms appear, and support earlier prevention strategies and improved recruitment for dementia clinical trials.
Biological age is a measure of how fast a person’s cells are aging, independent of their actual calendar, or chronological age. It estimates a person’s age by measuring biomarkers and can represent an individual’s overall health state.
While chronological age can only move forward, biological age can be younger or older than calendar age, depending on health and lifestyle factors.
Growing research suggests that a higher biological age, known as biological age acceleration, could serve as a reliable predictor of disease onset.
Now, new research led by scientists at King’s College London, in the United Kingdom, suggests a blood-based measure of biological age could help identify people at greater risk of developing dementia before clinical symptoms emerge.
Notably, the findings suggest that people whose biological age exceeded their chronological age were significantly more likely to develop dementia, particularly vascular dementia, and tended to develop the condition at a younger age.
Changes in these metabolites have previously been linked to age-related illnesses and premature mortality.
Using blood samples from more than 220,000 participants in the UK Biobank database, the research team calculated each individual’s biological age and compared it with their chronological age.
The resulting difference, called “MileAge delta,” indicated whether a person was aging faster or slower than expected.
Over the course of the study, nearly 4,000 participants developed dementia. The analysis suggests that those with a biological age exceeding their chronological age by more than one standard deviation, which accounted for roughly 16% of participants, had a 20% greater risk of developing dementia over time compared with people whose biological age was younger.
Notably, the risk was even more pronounced for vascular dementia, where accelerated biological aging was associated with a 60% higher likelihood of developing the disease.
Lead author Julian Mutz, PhD, King’s Prize Research Fellow at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, told Medical News Today he was not surprised by the strong link to vascular dementia.
“This partly reflects the type of data used to develop the metabolomic MileAge clock. The metabolites measured by the Nightingale Health metabolomics platform are predominantly lipids and lipoproteins, which are molecules closely linked to cardiovascular and metabolic health,” said Mutz.
“It is therefore not surprising that the clock is especially sensitive to vascular risk and by extension to vascular dementia,” he added.
While aging is the
The researchers discovered that combining biological aging data with genetic risk factors substantially improved dementia risk predictions.
Namely, individuals with advanced biological aging, who also carry two APOE4 gene variants, were up to 10 times more likely to develop dementia than the average participant in the study.
“The tenfold figure is striking but it is worth unpacking what is driving it,” Mutz explained to MNT. “APOE4 substantially raises risk and indeed is the strongest genetic risk factor for dementia. What our metabolomic clock adds is an additional non-genetic risk factor.”
“So while a tenfold increase is a very large, it reflects the combination of a powerful genetic risk factor with an indicator of biological aging. The important point is that these two sources of risk are complementary. And unlike genetic risk, metabolomic aging is potentially modifiable through lifestyle or clinical intervention.”
– Julian Mutz, PhD
The team also note that these two factors appear to act independently, suggesting distinct genetic and biological aging pathways linked to dementia.
While advancing age and genetic variants are known risk factor for dementia, the researchers emphasize that it is not an unavoidable condition.
Previous estimates suggest that approximately 45% of global dementia cases could be delayed or prevented through addressing modifiable risk factors, such as cardiovascular health, smoking, diet, exercise, and social isolation.
“The Lancet Commission on dementia identified 14 modifiable risk factors that together account for nearly 45% of dementia cases worldwide. Particularly relevant in the context of our study is reducing LDL cholesterol, given the metabolites included in our clock. Beyond that, the evidence supports increasing physical activity, quitting smoking and maintaining positive social relationships. Some of my other work on biological aging has looked at the impact of mental health conditions like depression, which are also risk factors for dementia. So the message is that there are multiple targets for reducing risk.”
– Julian Mutz, PhD
The researchers note that their findings could contribute to earlier diagnosis and intervention. Combining genetic and biological aging information could enable preventative strategies to help delay or even stop dementia in its tracks.
“The key message is that dementia risk is not determined by genetics alone. A substantial portion of risk is non-genetic and therefore potentially modifiable. That means there are things people can do — [such as] managing cardiovascular risk factors, staying physically active or looking after their mental health — that may slow biological aging and reduce their risk of dementia and other age-related diseases.”
– Julian Mutz, PhD
Based on their findings, the research team believe that blood plasma-based aging clocks could eventually become a practical tool for identifying higher-risk individuals in midlife, due to being minimally invasive and relatively scalable.
Additionally, the technology could also help to improve recruitment for clinical trials focused on dementia prevention or disease-modifying therapies.
“There are two ways this could help,” Mutz told MNT. “First, biological aging markers like MileAge could serve as outcome measures in trials.”
“Dementia takes many years to develop, which makes it difficult and expensive to use dementia incidence as a trial endpoint. A blood-based aging marker that can be measured at any time point could offer a practical way to assess whether an intervention likely impacts aging and, by extension, disease risk,” he added.
“Second,” Mutz detailed, “these markers could help identify and recruit individuals with older than expected biological age into trials, enriching the study population with people more likely to benefit from intervention.”
However, while the results are promising, the researchers caution that more research is still necessary before metabolomic aging clocks are introduced into routine clinical care. While the study highlighted an association between biological aging and dementia risk, it does not prove that accelerated biological aging directly causes dementia.
