A new and as-yet-unpublished study proposes a causative link between advanced glycation endproducts (AGEs) and DNA damage, potentially explaining the link between diabetes (where frequent blood glucose spikes cause accelerated formation of AGEs) and male infertility. The authors of the study focus on sperm, but the result suggests that AGEs may play a role DNA damage in other tissues as well. Since DNA damage is widely believed to play a causative role in the aging process, follow-up experiments could provide the long-awaited smoking gun connecting AGEs to fundamental mechanisms of aging — and breathe new life into the longstanding search for a clinical use for AGE-breaking compounds like Synvista‘s alagebrium.
(Hat tip to Longevity Meme.)
To be clear, tho’, what the press report says is not (as one might think, and as John Bayes once hypothesized (1) that glycation somehow directly damages the DNA, but that in the sperm of diabetics, the transcription of unspecified DNA repair enzymes was depressed. Leaving aside proteomics issues etc, this could very well result not from anything directly to do with glycation, but to the inhibition of DNA repair secondary to oxidative stress, which is elevated in diabetes & which is documented to impair several forms of DNA damage, presumably by dysregulating transcription thru’ REDOX-sensitive transcription factors etc.
Still damned interesting!
1. Baynes JW.
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2: Itzkowitz SH, Yio X.
Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation.
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Oxidative mutagenesis, mismatch repair, and aging.
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PMID: 15744047 [PubMed – in process]
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