Aging increases the risk of suffering cancer and cardiovascular and neurodegenerative diseases But its cellular and molecular mechanisms are still not well understood, and people of the same age can age at different rates without knowing why. Identifying biomarkers of aging is a great scientific challenge.
Now, an international study published this Wednesday in Nature has just presented innovative ‘molecular clocks’ capable of estimating age and life expectancy in multiple species of mammals.
To find biomarkers associated with aging, until now scientists have analyzed epigenetic modifications (non-genetic alterations) in DNA, but the new study has examined the transcriptome (the set of RNA molecules of an organism) of 11,000 tissue samples from humans, rodents and primates and has found conserved universal molecular signatures of aging (identical or very similar between species).
The study, led by Harvard University (United States) and carried out by researchers from Canada, Germany, Japan, Russia and Switzerland, has discovered that processes such as inflammation and senescence intensify over the years, while vital functions related to tissue regeneration tend to decrease.
The authors believe that identifying these specific biological processes could help improve health in old age and prolong longevity.
11,000 transcriptomes
By analyzing more than 25 types of tissues from mice, rats, macaques and humans, the researchers found conserved transnscriptomic signatures between species and cell types, allowing the identification of several genetic biomarkers of aging and mortality in mammals.
The authors observed a greater expression of genes related to death, that is, those associated with senescence (the decline of cell division), inflammation and apoptosis (programmed cell death) that were more activated in aged cells.
On the contrary, they observed a conserved decrease in the gene expression of regenerative processes such as those associated with healing, cell differentiation and extracellular matrix synthesis, which decreased their activity in all species and cell types with chronological aging.
The authors used these data to develop their own multi-tissue, multi-species molecular clocks to both assess chronological age and predict expected mortality.
They then validated these models using statistical approaches and against existing animal and cellular aging models.
The clocks predicted time to death with comparable accuracy to second-generation epigenetic clocks.
In addition, the real-time nature of transcriptomes on epigenetic data also allows the effectiveness of life-prolonging interventions to be assessed at the molecular level, the study notes.
Expert opinions
In a complementary ‘News & Views’ article also published in the journal Nature, João Pedro de Magalhães, from the University of Birmingham (United Kingdom), points out that the markers identified in this study “could help researchers specify which processes are modulated by interventions or diseases”, a valuable metric that is not visible through current methods.
However, he warns, further research is necessary to unravel exactly how these biomarkers are related to aging and whether they are the cause or simply consequences of the process.
Along the same lines, in statements to the SMC scientific resources platform, Ana Guerrero, Ramón y Cajal researcher at the Institute of Neurosciences of the University of Barcelona, believes that these findings could be useful to help identify people at greater risk of developing age-related diseases and refine their clinical follow-up.
Even so, he emphasizes, “the results should be interpreted with caution, since they probably reflect both driving mechanisms of aging and consequences of it,” therefore, he proposes studying these biomarkers in centenarians.
Also speaking to the SMC, Nabil Djouder, from the Spanish National Cancer Research Center (CNIO), points out that the observational nature of the study prevents us from knowing whether the transcriptional changes are a consequence or cause of aging and although it represents an important conceptual advance, “its clinical impact remains limited and will depend on demonstrating predictive utility and the ability to guide interventions in real contexts.”
For Martí Durán Ferrer, from the Biomedical Epigenomics group at IDIBAPS, the study shows that aging is a very complex process that advances at different rates in each organ and tissue.
“We have molecular aging clocks based on DNA methylation (epigenetics), blood plasma proteins (proteomics) and now also gene expression (transcriptomics). The challenge now is to understand what each molecular layer gives us and take advantage of this information to design therapeutic strategies that improve the natural aging process.”