SIRT6 and NF-kB link suggests aging is active process
Stanford researchers have revealed a link between two aging-related pathways, which will be published in the 9 January 2009 issue of Cell .
Researchers from Stanford University revealed today that they have found a link between SIRT6 and NF-kB – that the aging-related processes influenced by NF-kB are under the control of SIRT6, suggesting that aging is a deliberate, active process as opposed to the idea that it’s simply the accumulation of wear and tear over time.
“There is a genetic process that has to be on, and enforced, in order for aging to happen. It’s possible that those rare individuals who live beyond 100 years have a less-efficient version of this master pathway, just as children with progeria — a genetic aging disease — may have components of this pathway that are more active,” said Howard Chang, MD, PhD, associate professor of dermatology at the school and a member of Stanford’s Cancer Center.
SIRT6 is a member of the Silent Information Regulator proteins known as sirtuins that have been a major focus of life-extension efforts in recent years due to their enhanced expression in proven anti-aging modalities like caloric restriction. Little is mentioned about SIRT6 in anti-aging circles, however, with most of the attention focused on SIRT1, which is thought to be stimulated by chemicals like resveratrol.
Little is known about SIRT6, but Dr Katrin Chua, assistant professor of endocrinology, gerontology and metabolism at Stanford, has been studying it for several years. Sirtuins are involved in keeping the genome stable, making sure the correct genes are being expressed and unnecessary genes suppressed. A breakdown in this function is thought to be one of the root causes of aging, as increasing genetic dysregulation is thought to be the cause of the pathological effects of age.
Now, in addition to this function, Chang and Chua have found that SIRT6 regulates gene expression itself by binding to and inhibiting the ability of another protein, NF-kB, to stimulate the expression of genes that make cells age.
It’s been well established that NF-kB is strongly implicated in the aging process, and in searching for therapies to retard aging, the ability to inhibit NF-kB is a good sign. Blocking NF-kB in the skin cells of elderly mice causes these cells to behave as if they were young.
“It seems that an important job of SIRT6 is to restrain NF-kB and limit the expression of genes associated with aging. We’ve been interested in the activity of regulatory genes such as NF-kB during aging for several years now, and we were quite happy to find this very clear biochemical connection between these two pathways,” said Dr Chang.
Mice lacking SIRT6 die young, experiencing a rapid degeneration at about 4 weeks of age that coincides with elevated levels of NF-kB. When NF-KB is simultaneously blocked, the mice are able to live somewhat longer.
So, it seems that SIRT6 might be part of our aging-clock and NF-kB its instrument of death. Obviously, the story is much more complicated, but this seems to be an extremely exciting new lead in the search for what controls the aging process. I’m going to go and do some reading about SIRT6!
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