Aging is one SIRTainty in life: for uni- and multicelular lifeforms!

In Friday's issue of Cell magazine, an evolutionarily conserved protein, SIRT, takes the spotlight in the hit research drama, "Why we Weather with Age". Researchers from Harvard Medical school demonstrate that the part SIRT plays in DNA damage control during aging may be to blame for some of the ugly symptoms of growing old.

Mammalian protein SIRT, or SIR2 in unicellular yeast, normally sits on DNA to prevent unnecessary genes from being expressed in the wrong cells. Every gene is present in every cell in the body, but we wouldn't want our liver enzymes expressed in our brain cells. Thus, gene regulation is needed to determine the appropriate time and place for a gene to be expressed so that dangerous cellular consequences are avoided. SIR2 is a protein in yeast that has been known for years to silence inappropriate gene expression, but this key protein has another critical role to play during aging. SIRT is among the first responders to sites of DNA damage.

Needless to say, the older you get, the more DNA damage is present your cells: hence the wrinkles. So you might be grateful this Thanksgiving weekend that SIRT may be on task to fix those little DNA dings in your genetic machinery. Unfortunately, SIRT relocation to sites of DNA damage means the abandonment of its protective post on silenced genes. The unsilencing of unnecessary genes can have deleterious consequences for cells.

A consequence for aging yeast is sterility, which occurs when SIR2 goes AWOL to fix DNA damage, leaving a gene for sterility exposed and awaiting expression. This process has been studied well, but was thought to only be relevant to aging in yeast. Today's published findings by David Sinclair of Harvard Medical School and his colleagues demonstrate for the first time that the protective protein SIRT, works overtime in aging mice, picking up and moving to sites of DNA damage, while deserting the formerly repressed genes, which when expressed, are linked to various symptoms of aging.

Interestingly, when Sinclair feeds his mice a surplus of SIRT, they live significantly longer. “Our hypothesis was that with more [SIRT], DNA repair would be more efficient, and the mouse would maintain a youthful pattern [of] gene expression into old age.” Philipp Oberdoerffer, a researcher on Sinclair's team explains. Dr. Sinclair is working as a consultant for Genocea, Shaklee and Sirtris, a GSK company seeking to develop SIRT drugs for human use.

While we await a magical "forever young" drug, this publication serves as the first to suggest a shared mechanism for aging between two highly diverse organisms. The authors suggest the SIRT protein is a part of a universal mechanism for aging, which could be conserved across a variety of mammalian species, including humans. So as we begin to celebrate the close of yet another year, we can be hopeful that such mechanisms continue to be explored so that we might avoid the less desirable consequences of growing old.

image credit: http://www.cyber-heritage.co.uk/women/