Image courtesy of Emory UniversitySupposedly, you're only as old as you feel. Still, the molecular changes that take place in cells during aging may have something to do with how old (or young) someone feels.

An international team of researchers has taken a step forward in unraveling these processes, by studying the changes in gene expression levels in blood in more than 15,000 people around the world. This was the largest human molecular aging study to date.
 
The results were published on Thursday, October 22 in Nature Communications.
 
The team was led by researchers at the Erasmus Medical Center in the Netherlands (Marjolein Peters, MSc. and Joyce van Meurs, PhD) and the National Heart Lung and Blood Institute's Framingham Heart Study (Andrew Johnson, PhD) in collaboration with the CHARGE consortium. This large meta-analysis drew upon several existing studies, including data from 359 individuals from the Grady Trauma Project, based at Emory University and Grady Memorial Hospital.
 
In addition, Karen Conneely, PhD, assistant professor of human genetics at Emory University School of Medicine, led a meta-analysis investigating relationships between DNA methylation, aging and gene expression in several of the participating cohorts.
 
"Gene expression levels" is a precise way of saying how active a gene is. Human cells each have genes that encode proteins needed by many tissues, but many of those genes are not active in any given cell. DNA methylation is a chemical modification that does not change the A-C-G-T information in DNA, but it does influence whether a gene is going to be active or silent.
 
The researchers identified 1,497 genes whose activity in blood cells tended to consistently go up or down with aging. About 1,450 of them were not known to be linked with aging from previous studies. The researchers divided these genes into several groups that work together in areas such as metabolism, DNA repair and immune function.
 
In addition, the researchers found that age-association changes in gene expression co-occur with changes in DNA methylation, mostly in regulatory regions called enhancers. Enhancers act as "dimmer switches" to regulate the expression of nearby or distant genes. Because methylation can be influenced by environmental factors (such as diet, exercise or smoking, for example) these findings are a starting point for more research on anti-aging interventions.
 
The research team also developed a new calculator for predicting biological age based on gene expression profiles. Participants with a biological age higher than their chronological age tended to have adverse disease risk profiles, such as higher blood pressure and or cholesterol levels. Conversely, some participants had a biological age that was lower than their chronological age. The calculator is a tool that could allow other researchers analyzing gene expression data from human studies to predict biological age and assess whether participants are aging faster or slower than expected.

Additional Emory authors include: Alicia K. Smith, PhD, assistant professor of psychiatry and behavioral sciences and director of the psychiatric genetics core, and Genetics and Molecular Biology graduate student Elizabeth M. Kennedy.