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What Does a Century Do to A Genome?

The difference between a newborn and a nonagenarian is more than skin deep, going all the way down to their genes — or at least a particular modifier of those genes, new research finds.
/ Source: LiveScience

The difference between a newborn and a nonagenarian is more than skin deep, going all the way down to their genes — or at least a particular modifier of those genes, new research finds.

The study found that while people's genes remain the same, modifications to the molecular structure of the genome, what's called the epigenome, change how much protein they produce, and as a result, how cells function.

Older individuals were found to have fewer of these modifications than newborns do, which could be linked to age-related changes to the body and mind, the researchers said. [ 7 Ways the Mind and Body Change With Age ]

Genetic changes

The epigenome is a molecular marking system that uses chemical signals to turn gene expression  up and down without altering the DNA sequence. In a sense, the epigenome is the genome's boss.

The most common epigenetic modification is known as a methylation, a process that adds a methyl group (one carbon atom with three hydrogen atoms attached) to a specific sequence of DNA. The addition of a methyl group to one of these sites decreases how often that gene is used to make its specific protein and to carry out one function or another.

Researchers knew that epigenetic modifiers of certain genes changed over time, but had never before looked at the entire epigenome — all 16 million methylation sites — at different times of life.

Young vs. old

To do so, the researchers took genetic samples from white blood cells of a centenarian and several individuals over 90, and from infants, and checked to see how many of the potential methylation positions had a methyl group attached. It turns out that the newborn had more methyl groups attached to their genomes than the older individuals did. Newborns had methyl groups in 80 percent of the possible DNA spots, compared with 73 percent for the nonagenarians.

The researchers also looked at the methylation pattern of younger adults, including a 26-year-old, whose methylation level was 77 percent, falling midway between that of the older person and the newborn.

"The middle-aged patients are in the middle between the newborn and the centenarians. They have a half-distorted epigenome, indicating that it is a gradual process," study researcher Manel Esteller, of the Bellvitge Biomedical Research Institute in Spain, told LiveScience in an email.

This could just be a factor of aging. As people age, the activity of the proteins that add these methyl groups may drop off, or may be sent to different parts of the genome by accident, Esteller said. If these proteins aren't working correctly, then when the genome is copied to make a new cell, the new cell might not have all the same methyl modifications as its parent cell.

Lifetime of changes

Over time the accumulation of these missing methylations could cause diseases, the researchers said. Specifically, the older person's white blood cells "start to express genes that are typical of other tissues and organs," Esteller said. For these cells, which help to defend against foreign invaders, this is bad and "interferes with the cellular functions."

These changes in white blood cells could cause the higher risk of infection found in older populations, Esteller said. Over time, other changes to cancer-related genes could also explain why older people are more prone to cancer.

The study was published today (June 11) in the journal Proceedings of the National Academy of Sciences.

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