In their pursuit of assessing biological aging, which pertains not solely to the number of years a person has lived but also to the wear and tear on their organs and cells, scientists have developed numerous tools. Many of these instruments function as epigenetic “clocks,” counting chemical markers on DNA that accumulate with age and stress exposure; however, their reliability is not always guaranteed.
Researchers have now engineered novel biological clocks, grounded in gene activity, that demonstrate accuracy in predicting lifespan and identifying characteristic signs of chronic diseases. The findings of this study have been published in the journal Nature.
This does not imply that it can precisely state the remaining days until one departs this mortal coil.
Nevertheless, the researchers discovered that their newly developed methodology is quite effective at estimating how far along in life an individual or animal is likely to be.
According to the research team, an algorithm based on biomarkers will prove beneficial for analyzing the pace of biological aging across various species, including humans, and for understanding when this aging process accelerates or decelerates.
These new biological clocks are referred to as transcriptomic clocks. They analyze RNA molecules, which translate genes into proteins, to discern which genes are active and which are inactive. As this activity fluctuates with age, the resulting information can serve as an aging indicator.
A significant innovation involved the compilation of a large dataset from four animal species—mice, rats, macaques, and humans—followed by a comparison of aging processes both between these animals and across different bodily parts.
“Aging and medical interventions impact health and mortality, yet the underlying molecular mechanisms of these changes remain unclear,” the researchers stated in their paper. “We developed multi-species, multi-tissue transcriptomic clocks of chronological age and mortality expectation based on over 11,000 samples from four mammalian species, addressing the need for interpretable aging biomarkers that generalize across organs and species while reflecting health status.”
The investigators found that genes associated with processes like healthy cell division and wound healing act as indicators of slower molecular aging, while genes linked to cell death and inflammation are markers of more rapid aging and an older biological age.
The obtained results were subsequently adapted to create new molecular clocks, which were then validated on alternative aging models and through statistical analysis.
These clocks were shown to correctly assess the deceleration or acceleration of biological aging, as well as mortality risk. By utilizing human blood samples, they could predict the time until death, alongside the most effective epigenetic clocks.
Furthermore, the method allowed for the identification of well-known aging contributors, such as chronic diseases, in animal models of these conditions and in patient tissue samples.
The researchers believe this novel approach may be simpler to use and more informative than epigenetic clocks that have been available since 2013.
The genetic signatures of aging turned out to be surprisingly similar across all four species, indicating a notable overlap. This similarity was also observed in several cell types, including muscle and blood cells.
“The same genes are associated with aging, for instance, in the liver and heart of rats and humans,” stated Alexander Tyshkovsky, the study’s lead author from Harvard Medical School. “Even though these cells perform vastly different functions and have entirely distinct origins, they still share common aging-related biomarkers.”
This commonality suggests that these biomarkers might be genuine indicators of aging, though it is not yet understood if they contribute to the aging process in any way.
“It has long been known that gene expression levels of genes protecting against and responding to cellular stress increase with age, suggesting adaptive responses rather than causal roles,” wrote João Pedro de Magalhães, a molecular biologist at the University of Birmingham.
While we have limited ability to alter the aging process itself, the speed at which our biological aging clocks operate can be influenced by several factors. A healthy diet can help slow them down, whereas illnesses and environmental pollution tend to accelerate them.
One potential application of this new analytical tool lies in evaluating the effectiveness of various interventions. It could be employed to study the impact of lifestyle changes or medications on biological aging without the necessity for lengthy tests or trials.
This remains an assessment tool, and in many cases, it will not supplant such tests or clinical trials; however, it can be utilized for early diagnosis.
Further development of this methodology still requires significant effort, including additional testing on more diverse populations and a more precise definition of aging markers, but it appears poised to become another valuable resource in aging research.
“This study reveals conservative signatures and a modular architecture of mortality regulation, providing a framework for quantifiable assessment and targeted intervention in the aging of cellular subsystems across species and tissues,” the researchers concluded.
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