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DNA Helix

Posts Tagged ‘aging’

A Step Closer to Immortality?

I just read a short, interesting piece at the Telegraph about an increasing population of jellyfish that can apparently reverse their aging. I’m not entirely sure how this is possible and will be reading through published papers to see if I can figure it out.

From what I gather from the mainstream article, the cells dedifferentiate. Perhaps some of the pathways used are still present in humans? This species most likely has modified pathways that wouldn’t be the same in humans, and if they are unused in us chances are they are no longer in tact due to no selection pressure to maintain them. It could give some interesting clues about which areas to focus on for human aging research. Perhaps once day we will also be able to grow “younger” instead of just older. I’m sure Malthus would not be pleased…

In scientific first, Einstein researchers correct decline in organ function associated with old age

Josh: This is certainly an interesting study. I suppose the primary question I have is why do cells decrease the expression of the lysosomal receptors with age? Knowing that would be helpful, I think not only for aging and neurodegenerative research, but also for cancer research. Too bad this won’t really be a realistic treatment in its current state…however, perhaps a drug could be used to increase expression.

As people age, their cells become less efficient at getting rid of damaged protein — resulting in a buildup of toxic material that is especially pronounced in Alzheimer’s, Parkinson’s disease, and other neurodegenerative disorders.

Now, for the first time, scientists at the Albert Einstein College of Medicine of Yeshiva University have prevented this age-related decline in an entire organ — the liver — and shown that, as a result, the livers of older animals functioned as well as they did when the animals were much younger. Published in the online edition of Nature Medicine, these findings suggest that therapies for boosting protein clearance might help stave off some of the declines in function that accompany old age. The study’s senior author was Dr. Ana Maria Cuervo, associate professor in the departments of developmental & molecular biology, medicine and anatomy & structural biology at Einstein.

The cells of all organisms have several surveillance systems designed to find, digest and recycle damaged proteins. Many studies have documented that these processes become less efficient with age, allowing protein to gradually accumulate inside cells. But aging researchers continue debating whether this protein buildup actually contributes to the functional losses of aging or instead is merely associated with those losses. The Einstein study was aimed at resolving the controversy.

One of these surveillance systems — responsible for handling 30 percent or more of damaged cellular protein — uses molecules known as chaperones to seek out damaged proteins. After finding such a protein, the chaperone ferries it towards one of the cell’s many lysosomes — membrane-bound sacs filled with enzymes. When the chaperone and its cargo “dock” on a receptor molecule on the lysosome’s surface, the damaged protein is drawn into the lysosome and rapidly digested by its enzymes.

In previous work, Dr. Cuervo found that the chaperone surveillance system, in particular, becomes less efficient as cells become older, resulting in a buildup of undigested proteins within the cells. She also detected the primary cause for this age-related decline: a fall-off in the number of lysosomal receptors capable of binding chaperones and their damaged proteins. Could replenishing lost receptors in older animals maintain the efficiency of this protein-removal system throughout an animal’s lifespan and, perhaps, maintain the function of the animal’s cells and organs as well?

To find out, Dr. Cuervo created a transgenic mouse model equipped with an extra gene — one that codes for the receptor that normally declines in number with increasing age. Another genetic manipulation allowed Dr. Cuervo to turn on this extra gene only in the liver and at a time of her choosing, merely by changing the animals’ diet.

To keep the level of the receptor constant throughout life, Dr. Cuervo waited until mice were six months old (the age that the chaperone system’s efficiency begins to decline) before turning on the added receptor gene. When the mice were examined at 22 to 26 months of age (equivalent to approximately 80 years old in humans), the liver cells of transgenic mice digested and recycled protein far more efficiently than in their normal counterparts of the same age — and, in fact, just as efficiently as in normal six-month old mice.

Does maintaining efficient protein clearance in liver cells of an older animal translate into better functioning for the liver as a whole? Since a key function of the liver is metabolizing chemicals, Dr. Cuervo answered this question by injecting a muscle relaxant into very old transgenic mice and very old normal mice. The very old transgenic mice metabolized the muscle relaxant much more quickly than very old normal mice and at a rate comparable to young normal mice.

“Our study showed that functions can be maintained in older animals so long as damaged proteins continue to be efficiently removed — strongly supporting the idea that protein buildup in cells plays an important role in aging itself,” says Dr. Cuervo. “Even more important, these results show that it’s possible to correct this protein ‘logjam’ that occurs in our cells as we get older, thereby perhaps helping us to enjoy healthier lives well into old age.”

Dr. Cuervo next plans to study animal models of Alzheimer’s, Parkinson’s and other neurodegenerative brain diseases to see whether maintaining efficient protein clearance in the brain might help in treating them. “Most people with these conditions are born with a mutation that gives rise to defective proteins, but they don’t experience symptoms until later in life,” says Dr. Cuervo. “We think that’s because their protein-clearance systems can handle abnormal proteins when the person is younger but get overwhelmed as their efficiency falls with age. By preventing this decline in protein clearance, we may be able to keep these people free of symptoms for a longer time.”

Dr. Cuervo will also investigate whether maintaining efficient protein clearance in all the body’s tissues will influence longevity and prevent the functional losses associated with growing old. “There’s reason to hope that drugs exerting a similar effect throughout the body may help us enjoy healthier lives well into old age,” says Dr. Cuervo. Meanwhile, she notes, evidence is mounting that two dietary interventions —low-fat and calorie-restricted diets — help cells to maintain efficient protein clearance.

Source : Albert Einstein College of Medicine

Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Cong Zhang & Ana Maria Cuervo. Nature Medicine. Published online: 10 August 2008; | doi:10.1038/nm.1851

Prevailing theory of aging challenged in Stanford worm study

Josh: Certainly this study needs to be repeated and verified by other parties, since the traditional understanding of aging is not so much the “rusting out” of cells, but rather, the irreparable damage of their DNA. Eukaryotic cells, like those in animals, have telomeres on the ends of the chromosomes. These telomeres shorten every time the cell divides, but an enzyme called telomerase makes them longer again. However, telomerase gets turned off, or at least gets very down regulated, as our cells mature and we age. Thus, the cells can only divide a fixed number of times before the telomeres disappear and DNA damage occurs. In almost all cancer cells, telomerase has been re-activated, allowing the cells to divide indefinitely.

Age may not be rust after all. Specific genetic instructions drive aging in worms, report researchers at the Stanford University School of Medicine. Their discovery contradicts the prevailing theory that aging is a buildup of tissue damage akin to rust, and implies science might eventually halt or even reverse the ravages of age.

“We were really surprised,” said Stuart Kim, PhD, professor of developmental biology and of genetics, who is the senior author of the research. … Continue Reading »

Life-extending protein can also have damaging effects on brain cells

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

Another new wrinkle in treating skin aging

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).

Eliminating germline lengthens fly lifespan, Brown study shows

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 »

Researchers uncover details about how dietary restriction slows down aging

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 could delay biological aging by up to 12 years

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 »