DNA Damage and Reproductive Aging

Researchers here dig into the mechanisms by which female capacity for reproduction diminishes with age. This produces an interesting data point to add to the debate over the degree to which nuclear DNA damage might be a contributing cause of aging:

A woman's eggs decline in quality and quantity as she ages, at least in part because an important DNA repair pathway becomes impaired. The pathway, which includes proteins encoded by the well-known BRCA genes, is supposed to repair double-strand breaks in DNA. But as women get older, the study found, repair mechanisms lose efficiency and reproductive cells accumulate damaged genes and often commit suicide.

While women are born with 1 million oocytes, only about 500 turn into full-fledged eggs over their lifetime. By the time women reach their early 50s, the remaining oocytes have almost completely degraded. Why the oocytes degrade so rapidly in comparison to other body tissues was a mystery.

[Researchers] first tested mouse and human oocytes for double-strand breaks and found that the damage increased significantly with age. They also looked at expression of several repair proteins in the cells. Expression of BRCA1 and a handful of other repair genes decreased with age. The results implied that dysfunction in DNA repair may lead to genomic damage seen in aging oocytes.

The researchers studied both mice and women with mutations in the BRCA1 [gene]. People with mutations in BRCA1 had lower oocyte reserves in their ovaries than those without the mutations, and mice with BRCA1 mutations had smaller litters of pups than wild type mice.

Link: http://www.the-scientist.com/?articles.view/articleNo/34375/title/Why-Women-s-Eggs-Don-t-Last/

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