Aging and mortality has been a fascinating topic of interest recently, particularly in the field of epigenetics. What are the chemical DNA markers of age? Can we look at someone’s epigenome to determine their risk for death? Could we reverse these epigenetic tags to restore youth or undo the pesky physical characteristics and diseases that come with getting old? And are there lifestyle changes we may need to make to epigenetically improve our own health?
Although we are far from achieving and applying “fountain of youth” ideals in therapies or controlled drugs, researchers are beginning to pinpoint certain genes that epigenetic tags attach to, which are connected to aging and health. For example, earlier studies have shown that there’s a link between a particular histone modification known as histone acetylation and physiological alterations related to age, among other things.
In a new study, researchers from Germany created an epigenetic risk profile, predicting one’s likelihood of death based on the epigenetic mechanism known as DNA methylation at particular genes. Furthermore, their results show that smoking may be the most epigenetically detrimental lifestyle activity.
For fourteen years, a team of scientists headed by Hermann Brenner from the German Cancer Research Center in Heidelberg along with their colleagues from the Saarland Cancer Registry and the Helmholtz Research Center for Environmental Health in Munich investigated DNA methylation and what it reveals about someone’s health and his or her mortality risk.
DNA methylation is one of the most popular epigenetic mechanisms and is defined as the addition of a methyl group to DNA, which is catalyzed by an epigenetic enzyme known as DNA methyltransferase (DNMT). This chemical tag is known to suppress gene expression and can be brought upon by lifestyle and environmental factors.
The group looked rigorously at the DNA of blood cells from 1,900 participants and searched for a statistical link connecting methylation levels and the individuals’ survival. From over 500,000, they narrowed down 58 CpGs, which are a combination of certain building blocks of DNA, that very strongly linked methylation status to mortality. Looking at these marks could theoretically tell us whether someone is more or less at risk to die, but this type of research has a long way to go before it is able to make steadfast conclusions.
The Strongest Lifestyle Risk Factor
The CpG islands were located in areas that previous research has already connected to diseases. Twenty two of these locations were actually identical to the methylation positions that the lead scientist, Brenner, and his team had uncovered in a previous study on smoking and epigenetics. According to their results, smoking tobacco is the strongest factor that leaves methyl marks on genes related to disease and morbidity.
“It appears worthwhile pointing out that prevention of or intervention on smoking-related [DNA methylation] changes may provide major improvement in premature death prevention, given the reversibility of smoking-induced methylomic aberrations,” the researchers reported.
“The good news is that the level of DNA methylation is not written in stone,” Brenner added. “Unlike mutations in the DNA building units, it is reversible. That means, for example, that an unfavorable methylation status may change after smoking cessation and the mortality risk may drop again significantly.”
Epigenetic Risk Profile
The researchers selected ten CpGs which exhibited the strongest association with mortality and constructed a mortality risk score. These associations are independent from the “epigenetic clock”, recently coined by Steve Horvath and his team, and offer new insight into precise genes and areas that account for morbidity risk.
Individuals in the study whose DNA showed an unfavorable methylation profile at five or more of these sites on the genome had a 7 times greater risk of death within the 14 year study period, compared to those who had normal methylation at those sites.
Additionally, they found that this epigenetic risk profile was a more accurate way to determine lifespan than all other previously established genetic risk profiles based on changes to the genome.
“We were surprised that the methylation status of only ten positions of our genome correlates so strongly with all-cause mortality,” said Brenner. “We found even stronger links to mortality from cardiovascular diseases. Now it is important to find out which prevention measures are most effective to achieve a beneficial impact on the methylation profile and mortality.”
In moving forward with epigenetic aging research, it will be helpful to keep in mind that an accelerated internal epigenetic clock may lead to an earlier death for some regardless of lifestyle and that different ethnic groups may epigenetically age slower. Even with all the unknowns surrounding these studies, it’s an exciting time for the study of epigenetics and aging.
Source: Zhang, Y. (2017). DNA methylation signatures in peripheral blood strongly predict all-cause mortality. Nature Communications, 8: 14617.
Reference: Koh. DNA labels predict mortality. Deutsches Krebsforschungszentrum. 20 Mar 2017. Web.