If you look around at your friends and family, it is clear our biological clocks tick differently. Women tend to live longer than men do, some individuals can look years younger – or older – than their chronological age, and diseases can affect our aging process.
The University of California, San Diego School of Medicine led a new study, published online in the journal Molecular Cell, that describes markers and a model that quantifies how aging occurs at the level of genes and molecules. This provides a more precise way to determine how old someone is, and also perhaps anticipate or treat ailments and diseases that come with the passage of time.
“It’s well known that people age at different rates,” said Kang Zhang, MD, PhD, professor of ophthalmology and human genetics at the Shiley Eye Center and director of the Institute for Genomic Medicine, both at UC San Diego. “Some people in their 70s look like they’re in their 50s, while others in their 50s look like they’re in their 70s.”
Precisely quantifying the actual rate of aging in individuals and identifying markers has been challenging, however. Researchers have been looking at telomeres, for example. Telomeres are repeating nucleotide sequences that cap the ends of chromosomes which shorten with age. The researchers have found that other factors, such as stress, can affect the telomeres as well.
Dr. Zhang and his colleagues, including scientists from Sage Bionetworks, UCSD Institute for Genomic Medicine, and Johns Hopkins University among others, focused on DNA methylation, which is a fundamental, life-long process in which a methyl group is added or removed from the cytosine molecule in DNA to promote or suppress gene activity and expression. More than 485,000 genome-wide methylation markers were measured in blood samples of 656 persons ranging in age from 19 to 101.
According to Zhang, this is a robust way of predicting aging that has subsequently been validated on a second sampling of several hundred blood samples from a separate cohort of human individuals.
The team found that a person’s “methylome”, which is the entire set of human methylation markers and changes across a whole genome, predictably varies over time. This provides a way to determine a person’s actual biological age from a blood sample.
“It’s the majority of the methylome that accurately predicts age, not just a few key genes,” said Trey Ideker, PhD, a professor of medicine and chief of the Division of Medical Genetics in the UC San Diego School of Medicine and professor of bioengineering in the Jacobs School of Engineering. “The methylation state decays over time along the entire genome. You look in the body, into the cells, of young people and methylation occurs very distinctly in some spots and not in others. It’s very structured. Over time, though, methylation sites get fuzzier; the boundaries blur.”
These boundaries do not blur, however, at the same rate in everyone. The researchers found that at the molecular level it was clear that individual bodies age at varying rates. Even within the same body, they said, different organs age differently. To add another layer of complication, cancer cells age at a different rate than their surrounding healthy cells. These findings have broad practical implications, for example, they could be used in forensics to determine a person’s age based only upon a blood or tissue sample.
Zhang says that one of the most profound findings of this study is that the methylome provides a measure of biological age, in other words, how quickly or slowly a person is experiencing the passage of time. This kind of information could have a potentially huge medical importance.
“For example, you could serially profile patients to compare therapies, to see if a treatment is making people healthier and ‘younger.’ You could screen compounds to see if they retard the aging process at the tissue or cellular level.”
By identifying lifestyle changes that might slow molecular aging, assessing an individual’s methylome state could improve preventive medicine. Ideker noted that much more research remains to be done, however.
“The next step is to look to see whether methylation can predict specific health factors, and whether this kind of molecular diagnosis is better than existing clinical or physical markers. We think it’s very promising,” Ideker said.