Two people of very different ages can have a similar level of biological aging in their brains. Such an occurrence is possible because aging and metabolic health follow two distinct pathways that influence brain health. While it is known that the brain changes as we get older, a recent study analyzing more than 3,000 brain scans found that metabolic issues affect the brain through a different biological pathway than aging does.
The researchers found that the two axes operate independently of one another, meaning a person can be relatively young yet experience brain changes associated with poor metabolic health. These changes, driven by metabolic factors, were also linked to real-world cognitive performance.
People with poorer metabolic health generally struggled more with tasks that required cognitive flexibility, or the ability to shift between competing demands. The association was strongest in females.
The aging axis affects the brain by eroding its structural integrity. This includes thinning of the brain’s outer layer and vascular dysfunction, which slows the flow of blood through the brain’s vessels. The metabolic axis works differently. Instead of one main driver, it has an army of factors, including body weight, blood pressure and cholesterol, all acting together.
Their shared effect is a drop in cerebral perfusion, that is, less blood actually reaching the brain.
The findings are published in PLOS Biology.
Identifying brain-body markers
The brain and body are deeply connected. However, when scientists study aging, both components are examined separately, leading to an incomplete picture of the biological processes involved.
This disconnect stands out when considering that routine clinical markers such as BMI, blood pressure, blood lipids and glucose-related measures are easy to collect, yet it is still unclear how well they reflect brain health. In contrast, advanced MRI techniques can directly capture brain structure, connectivity and blood flow in detail, but they remain largely absent from routine clinical care.
The researchers set out to identify simple, easily obtained markers that could reliably reflect a person’s brain health. To do this, they first examined what basic health and background information might reveal about the brain. They then looked at which MRI-based brain measures—covering structure, activity and blood flow—are most closely linked to different aspects of physical health.
The team collected data from two large cohorts: 597 participants from the Human Connectome Project–Ageing (HCP–A), ages 36 to 100, to identify the main biological patterns linking body health and brain health, and 3,013 participants from the UK Biobank, ages 51 to 83, to test whether those patterns held in a separate group of people. Then they applied an advanced statistical tool called Partial Least Squares (PLS) to find relationships between the body data and all the brain data.
The researchers found that brain health is shaped not just by aging, but by two separate and independent “axes”: one linked to aging itself and the other to metabolic health. These patterns were seen in both males and females. Aging affects different regions of the brain, whereas poor metabolic health primarily targets the brain’s blood supply.
The researchers noted that the independent nature of both axes makes metabolic health a modifiable risk factor. While one cannot stop aging, people can manage their weight, cholesterol and blood pressure to protect the brain’s blood supply and, in turn, its health.
Future research using broader biomarker panels might help uncover deeper links between the body and the brain beyond metabolism. Until then, the findings make it clear that metabolic health is not just about the heart or diabetes, as it is directly tied to brain blood flow and cognition. As a modifiable factor, it deserves a more central place in public health messaging around brain health.
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Publication details
Asa Farahani et al, Aging and metabolism contribute separately to brain–body health, PLOS Biology (2026). DOI: 10.1371/journal.pbio.3003856
Journal information:
PLoS Biology
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