The clock is ticking on all our lives; we just don't know when it will stop.
Scientists have devised a host of tools in their attempts to gauge biological aging – not just how many birthdays a person has had, but how worn out their organs and cells are.
Many of these tools are epigenetic 'clocks', which tally chemical marks on DNA that accumulate with age and stress, but they aren't always reliable.
Now, researchers have developed a new clock based on gene activity that accurately predicts lifespan and captures hallmarks of chronic disease.
That's not to say it can tell you exactly how many days you've got left before you shuffle off this mortal coil.
But researchers found that their newly developed technique did pretty well at estimating how far through life a person or animal probably is.
According to the research team, the biomarker-based algorithm is going to be useful for analyzing rates of biological aging across species, including humans, and understanding when this aging speeds up or slows down.
The new clock is what's known as a transcriptomic clock: It analyzes RNA molecules that translate genes into proteins to figure out which genes are turned on and off. As this activity changes as we get older, the information can be used as a signature of aging.
One of the key innovations here was gathering a large set of data across four species – mice, rats, macaques, and humans – and then comparing aging processes between animals, and between different parts of the body.
"Aging and interventions modulate health and mortality, yet the underlying molecular mechanisms of this modulation remain unclear," write the researchers in their published paper.
"We developed multi-species, multi-tissue transcriptomic clocks of chronological age and expected mortality across more than 11,000 samples from four mammals, addressing the need for interpretable aging biomarkers that generalize across organs and species, while reflecting health status."
The team found genes associated with processes such as healthy cell division and wound repair acted as signs of slower molecular aging, while genes linked to cell death and inflammation were markers of faster aging and an older biological age.
These findings were then adapted into the new molecular clock, which was validated against other aging models and through statistical analysis.
The clock was shown to correctly assess slower or faster biological aging, as well as mortality risk. With human blood samples, it could predict time to death as well as the best epigenetic clocks.
What's more, it picked up known contributors to aging, such as chronic disease, in animal models of those diseases and tissue samples from human patients.
The researchers think this new approach could be easier to work with and more informative than epigenetic clocks, which have been around since 2013.
The genetic signs of aging were surprisingly conserved across all four species, which means they matched up to a notable degree. This consistency was shared across multiple cell types too, including muscle and blood cells.
"The same genes are associated with aging in, for example, liver and heart in rats and humans," the lead author of the study, bioinformaticist Alexander Tyshkovskiy from Harvard Medical School, told Jackie Flynn Mogensen at Scientific American.
"Even though the cells have very different functions, very different origins, they still share the same aging-related biomarkers."
That commonality suggests these biomarkers may be genuine signs of aging, though we don't know if they are contributing to aging in any way.
"The expression levels of genes that protect against and respond to cellular stress have long been known to increase with age, which is suggestive of adaptive responses, rather than causal drivers," João Pedro de Magalhães, a molecular biologist at the University of Birmingham, writes in a commentary on the study.
"It is therefore uncertain whether transcriptomic signatures drive age-
ing, result from it or represent compensatory mechanisms."
There's not much we can do about much of the aging process, but we do several factors affect how fast our biological aging clocks tick. A healthy diet can help slow them down, while disease and pollution tend to speed them up.
One way that this new analysis tool promises to be helpful is in testing the effects of different interventions. It could be used to see how lifestyle changes or drugs were impacting biological aging, without lengthy tests or trials.
It's still an estimation tool, and wouldn't replace those tests or clinical trials in a lot of cases, but could be used for early assessments.
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There's still plenty to do to develop this technique, including further testing on more diverse human populations and teasing out measurements of aging more precisely, but it looks like it could be another important resource for research into aging.
"This study reveals conserved signatures and a modular architecture of mortality regulation, providing a framework for quantifying and targeting aging of cellular subsystems across species and tissues," the researchers write.
The research has been published in Nature.