A Cellular Secret to Long Life

Longevity may depend in part on neatly spooling DNA.

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By Tina Hesman Saey, Science News

Just as proper storage keeps a loaf fresh longer, adequate packaging may be a key to cellular longevity, reports a study of the organisms that make bread rise.

New research on aging in baker’s yeast suggests that proper packaging of DNA can halt aging and lead to longer life. The study, published September 10 in Molecular Cell, shows that a decline in levels of DNA-packaging proteins called histones is partially responsible for aging, and that making more of the proteins can extend the life-span of yeast.

Aging has many different causes, says Jessica Tyler, a molecular biologist at the University of Texas MD Anderson Cancer Center in Houston. Now, Tyler and her colleagues think they have uncovered yet another way cells age—by losing histones.

Histones are important proteins that form a spool upon which DNA is wound. This spooling allows yards of DNA to fit inside a cell and also helps control how genes are turned on and off (SN: 5/24/10, p.14). Tight winding helps keeps genes off, while loosening the packaging allows genes to be turned on.

As yeast cells age they make fewer histone proteins, Tyler’s team found. In order to determine whether losing histones is a cause of aging, the researchers studied yeast lacking a protein called Asf1. Without the protein, genes encoding histones don’t get turned on as often, and fewer histones are made.

Yeast cells lacking Asf1 have drastically shorter life-spans than most yeast do, dividing only seven times on average instead of 27 times like normal yeast. The lack of histones is responsible for the shorter life-spans, the team demonstrated. Adding back histones made yeast without Asf1 live 65 percent longer. And making extra histones in normal yeast extended life-span up to 50 percent.

Exactly how histones determine how long yeast will live is still unknown. The researchers think falling levels of histones during aging may loosen DNA and allow many genes to be turned on inappropriately. That excess gene activity may zap a cell’s energy reserves. Making extra histones may help old yeast keep tighter control of gene activity. Tyler’s group is still testing that hypothesis.

In the new study, the team found that the histone life-extension process is likely independent of other known mechanisms for increasing life-span. For instance, histones appear to work differently from the well-known antiaging sirtuin protein Sir2.

But histones’ relationship to caloric restriction—a much-studied way of increasing life-span by cutting energy consumption while still giving an animal all the nutrients needed for survival—is more complicated. Yeast on restricted-calorie diets live longer. So do yeast with more histones. If the two mechanisms are entirely independent of each other, combining the two treatments should add up to make yeast live longer than either manipulation alone. Instead, combining the treatments in the new experiments led to a life-span extension somewhere in between the solo effect of either treatment.

The finding serves as a reminder that biological processes are complicated and intertwined, says Matt Kaeberlein, a molecular biologist at the University of Washington in Seattle. “When we think about these genetic pathways, we like to draw them in nice straight lines, but in reality they are all interconnected networks,” he says. “We need to have more studies exploring the relationship between histones and dietary-restriction effects on aging.”

“The next burning question is, ‘Are any of these mechanisms at play in the mammalian system?’” Kaeberlein says. Some evidence suggests that mice also lose histones as they age.


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