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Why do we age? Genomes of baby and 103-year-old may offer clue

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Why do we get decrepit as we age? Why does skin wrinkle, why do joints decay, organs stiffen and the brain atrophy and the body just generally stop working at its tip-top best, until ... the inevitable?

Scientists don’t know the answer but are exploring various theories. An interesting study comparing the genome of a newborn baby boy to that of a 103-year-old man may offer some clues.

The idea: Aging might be caused by decay in the precise way our genes are chemically programed.

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In the body, genes are decorated with little chemical tags to make sure each one is active only when and where it’s supposed to be active. That pattern will differ from cell to cell: You don’t want genes responsible for bone-formation turned on in the liver, nor those that carry instructions for making hair do their thing inside white blood cells. And so on.

One could imagine it would be bad news if this careful tagging started to fall apart. The new study, conducted by scientists in Spain and published in the journal Proceedings of the National Academy of Sciences, found what looks like decay in this careful regulation.

Specifically, the scientists looked at methylation -- the attachment of methyl groups -- of DNA. Methylation occurs at many sites in the genome and has the effect of turning down activity of a gene.

The researchers analyzed the genome of the baby’s white blood cells (obtained from cord blood). They found more than 16 million spots where methyl groups had been attached to the baby’s DNA.

But when they did the same thing with the old man’s DNA (obtained from his white blood cells), they found nearly 500,000 fewer sites with methyl groups attached. The sites weren’t as densely methylated either.

The scientists got a similar result when they looked in a larger group of 19 Caucasian newborns and 19 Caucasian nonogarians (average age 92.6). And they found an intermediate level of methylation when they examined the white-blood-cell DNA of 19 middle-aged people (average age about 60).

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The scientists went on to take a closer look at a few specific genes where they’d spotted changes in methylation in their samples and found that the activity of the genes that had been depleted in methyl groups was, indeed, changed. And they noted that some of the genes -- such as two called Sirtuin 5 and Sirtuin 7 -- are thought from other studies to be involved in the biology of aging.

That sirtuin-aging story is complex, mind you -- it’s a whole family of genes, and a recent study suggested that sirtuins may not be as key to the fountain of youth as had been supposed before. On the other hand, another recent study suggested that one of the sirtuin family expanded lifespan in mice.

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