The body has more than one clock, says new study
Researchers challenge the idea that biological ageing can be captured by a single universal clock. The evidence suggests that ageing is shaped by sex, organ and molecular system.
Imagine two people who are both 60. Chronologically, they are identical in age. Biologically, they may be anything but. One person’s brain may appear relatively young while their metabolic system shows signs associated with accelerated ageing. Another may have an older-appearing immune system but comparatively preserved brain biology.
Now add gender to the equation. The biological processes associated with ageing may not be distributed in exactly the same way in females and males. If so, a model that treats everyone as biologically equivalent could be smoothing away some of the very differences researchers are trying to detect.
That is the central proposition of a new multi-cohort and multi-researcher study published in Nature: Biological ageing may need to be measured in a way that accounts for both gender and organ, rather than assuming that one ageing clock can describe everyone.
To test that idea, researchers built 38 biological-ageing clocks covering 15 organ systems, drawing on three very different sources of biological information: proteins circulating in the blood, metabolites (small molecules that tell you what is happening in the body) and MRI measurements of organs. Crucially, they trained the models separately in females and males. They found that some aspects of ageing appear to be sex-specific, some appear to be organ-specific, and many are shared. That finding turns the biological-ageing clock from a simple measurement problem into a modelling problem.
What if there is no single biological age?
We know how old we are. It is the number on our birth certificate. But biological age is a different question. Scientists have been developing “ageing clocks” that try to estimate how old a person’s biology appears compared with others of the same chronological age. The hope is that these clocks might reveal why some people remain healthy into old age while others develop disease earlier. But there is a problem with the idea of a single number.
The study suggests that biological ageing may be better understood as a collection of different trajectories rather than a single score. Your brain could be ageing along one path, your immune system along another and your metabolic system along a third.
The researchers found that some ageing clocks worked better when females and males were modelled separately. This was particularly apparent for some measures involving body fat, the immune system and metabolism. But there was no universal advantage to splitting the sexes. In some cases, the separate models became less reliable because they had fewer people from which to learn.
Genes tell different stories
The researchers also looked at genetics and found 359 significant genetic associations across the ageing measures. Again, the patterns varied by sex and organ.
Some liver and metabolic ageing measures showed stronger genetic signals in females, while some immune, skin and spleen measures showed stronger signals in males. The interesting message is that different parts of the body may have different mixtures of genetic and environmental influences—and those mixtures may differ between females and males.
In other words, there may be no single genetic blueprint for ageing.
An older organ may have different causes
The researchers linked seven imaging-based ageing measures to 2,923 proteins circulating in the blood. The proteins associated with older-appearing organs differed between females and males. That does not mean scientists have discovered a “female ageing protein” or a “male ageing protein”.
Instead, it suggests that two people whose brains, for example, appear biologically older may have arrived at that state through different molecular pathways. That possibility could eventually matter for personalised medicine.
Can an ageing clock see disease coming?
Using long-term health records, the researchers found that some biological-ageing measures were associated with diseases that developed later, including high blood pressure, high cholesterol and type 2 diabetes. Associations were also found with several other conditions and with mortality.
But an association is not the same thing as causation. A clock may identify a biological state associated with disease without being the thing that causes the disease. Even sophisticated genetic analyses cannot by themselves prove that making an ageing clock look “younger” would prevent illness.
What about Alzheimer’s?
Among people who already had mild cognitive impairment, those with older-appearing brains were more likely to progress to Alzheimer’s disease. The association appeared in both men and women. But when the researchers directly compared the two groups, the difference between them was not statistically significant.
The end of the single ageing clock?
Hormones, menopause, hormone therapy, reproductive history, lifestyle and environmental exposures can all influence ageing. The genetic analyses also focused on people of European ancestry. Whether the same patterns apply across South Asian, African, East Asian, indigenous and other populations remains an open question. And the clocks still need extensive testing in independent populations. Instead of telling someone, “Your biological age is 63,” the future might describe something more nuanced:
Your brain is ageing along one trajectory, your metabolic system along another, and your immune system along a third. For now, ageing clocks remain research tools, not crystal balls.