Proteins widely believed to protect against aging can actually cause oxidative damage in mammalian brain cells, according to a new report in the July Cell Metabolism, a publication of Cell Press. The findings suggest that the proteins can have both proaging and protective functions, depending on the circumstances, the researchers said.

” Sirtuins are very important proteins,” said Valter Longo of the University of Southern California, Los Angeles. “Overexpression can protect in some cases, and in other cases, it may do the opposite. It has to do with the fact that they do so many things.”

Sirtuins, or Sir2 family proteins, are found in organisms from bacteria to humans. Sir2 controls aging and life span in yeast, the worm C. elegans, and Drosophila fruit flies, earlier studies have shown.

Studies have also implicated Sir2 in the life-extending effects of a calorie restricted diet in some, though not all, organisms. Notably, Longo’s lab showed that lack of Sir2 in yeast further extended the life span of calorie-restricted cells.

SirT1, the mammalian version of yeast Sir2, controls numerous physiological processes including glucose metabolism, DNA repair, and cell death, the researchers added. In mammalian cells, SirT1 also controls several stress-response factors.

Now, the researchers show that cultured rat neurons treated with a SirT1 inhibitor more often survived treatment with oxidative stress-inducing chemicals. They further show evidence to explain the mechanism responsible for that effect.

They also found lower oxidative stress levels in the brains of mice without SirT1. However, those SirT1 knockout mice didn’t live as long as normal mice do on either a normal or a calorie-restricted diet.

These results are consistent with the existence of a prooxidative stress role for mammalian SirT1 similar to that described for Sir2 in yeast but confirm that sirtuins can play both positive and negative roles, Longo said. Based on the new findings, Longo urges caution to those developing SirT1-boosting drugs intended for human consumption.

” [Such drugs] could have beneficial effects for certain diseases, but again, these proteins do a lot of things,” he said. “I would say the idea that there is a conserved action of sirtuins to cause major life span extension—the foundations for that are weak or very weak. Until we have more data to show that chronic treatment to increase SirT1 activity does not do damage, I don’t think it’s a good idea.”

Source: Cell Press

Topical applications of a naturally occurring fat molecule have the potential to slow down skin aging, whether through natural causes or damage, researchers report.

Through both the normal aging process and external factors like UV damage, smooth, young skin inevitably becomes coarse and wrinkled. The basis of this wrinkling is that time and damage both lower the production of new collagen while increasing the levels of enzymes called MMPs that chew up existing collagen.

Covering up, slowing down, or even stopping the wrinkling process has become a big business, and as part of this research endeavor, Jin Ho Chung and colleagues tested seven naturally occurring lipids (greasy molecules that play many important biological roles) in their ability to reduce skin aging.

In samples of skin cells, three of the lipids could prevent UV-radiation from both reducing collagen expression and increasing the levels of MMPs; they even increased collagen in undamaged skin cells. Of these three, the molecule phosphatidylserine (PS) seemed the most promising, so the researchers tested it on human skin.

They applied a 2% PS solution to small areas of the buttock in both young and old volunteers; the young skin was subsequently given a dose of UV-radiation to simulate sun damage. In both natural and UV-induced aging, PS treatment prevented collagen reduction and an increase in MMPs when compared to no treatment.

While larger and longer trials are needed to confirm any therapeutic benefits, these initial findings suggest topical PA application might be a simple and natural way to slow down the biological elements underlying wrinkling.

Source: American Society for Biochemistry and Molecular Biology

Phosphatidylserine prevents UV-induced decrease of type I procollagen and increase of MMP-1 in dermal fibroblasts and human skin in vivo. Cho et al. Journal of Lipid Research. 49 (6): 1235. (2008).

Josh says:

I’m sure a lot of women will love to hear this. It would make a great alternative to using Preparation H to get rid of wrinkles (see page 2).

New research by Brown University biologists shows that fruit flies live longer when they don’t produce germline stem cells – the cells that create eggs and sperm.

The work suggests a provocative general principle at work: Signals from reproductive tissue directly control lifespan and metabolism in the whole organism. The work, which appears in the Proceedings of the National Academy of Sciences, also offers a first glimpse of how this control in the fly might occur at the molecular level.

“For more than 50 years, scientists have known that there is a link between reproduction and lifespan,” said Thomas Flatt, a postdoctoral research fellow in the Department of Ecology and Evolutionary Biology at Brown and the lead author of the research article. “When reproduction is delayed, animals live longer. Why? Our research suggests that signals from the reproductive system can regulate aging in animals – including, possibly, humans.” … Continue Reading »

University of Washington scientists have uncovered details about the mechanisms through which dietary restriction slows the aging process. Working in yeast cells, the researchers have linked ribosomes, the protein-making factories in living cells, and Gcn4, a specialized protein that aids in the expression of genetic information, to the pathways related to dietary response and aging. The study, which was led by UW faculty members Brian Kennedy and Matt Kaeberlein, appears in the April 18 issue of the journal Cell.

Previous research has shown that the lifespan-extending properties of dietary restriction are mediated in part by reduced signaling through TOR, an enzyme involved in many vital operations in a cell. When an organism has less TOR signaling in response to dietary restriction, one side effect is that the organism also decreases the rate at which it makes new proteins, a process called translation. … Continue Reading »

Maintaining aerobic fitness through middle age and beyond can delay biological aging by up to 12 years and prolong independence during old age, concludes an analysis published ahead of print in the British Journal of Sports Medicine.

Aerobic exercise, such as jogging, improves the body’s oxygen consumption and its use in generating energy (metabolism).

But maximal aerobic power starts to fall steadily from middle age, decreasing by around 5 ml/[kg.min] every decade.

When it falls below around 18 ml in men and 15 ml in women, it becomes difficult to do very much at all without severe fatigue. … Continue Reading »

Perhaps the aging process can’t be stopped. But it can be predicted, and new research from Tel Aviv University indicates that people may live longer and lead healthier lives as a result.

Researchers have developed a new biological marker that represents the age of a body’s bones. It reveals that the speed of physical aging is strongly influenced by genetics.

Christened the osseographic score (OSS), this new marker can be used by doctors as a scientific tool for predicting a person’s general functioning and lifespan, says Tel Aviv University scientist Dr. Leonid Kalichman, an instructor at The Stanley Steyer School of Health Professions. He is a co-author of the study published in Biogerontology and the American Journal of Human Biology (2007), which was conducted in partnership with Dr. Ida Malkin and Prof. Eugene Kobyliansky, both from the Sackler Faculty of Medicine at Tel Aviv University. … Continue Reading »

Scientists have identified a fusion protein that may contribute to Cockayne syndrome, a devastating disease characterized by developmental defects, neurodegeneration, severe wasting, and premature aging. The study is described in an article published March 21 in the open-access journal PLoS Genetics.

Genetic defects in certain DNA repair factors like the CSB protein have been known for some time to cause premature aging, but the reasons are still unclear. Most cases of Cockayne syndrome (CS) are caused by recessive mutations in the CSB gene, yet some individuals with inherited mutations that cause complete loss of the CSB protein are nearly unaffected. The implication is that CS is not caused solely by loss of functional CSB protein, but by continued expression of CSB-related proteins or protein fragments. … Continue Reading »