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Senior Citizen Longevity & Statistics

New Reports Point Ways to Extend Longevity – at Least for Naked Mole Rats and Roundworms

Naked mole rats live longer with better protein creation; roundworms find fountain of youth in niacin (vitamin B3) that tricks body into thinking it is exercising

Sept. 30, 2013 – It there is anything that grabs the attention of senior citizens it is probably information about longevity – ways to extend our lives There are two research reports out today on success at extending life, at least when it comes to naked mole rates and roundworms.

Naked mole rats have what any animal would want. They live long lives - about 30 years - and stay healthy until the very end. Now biologists at the University of Rochester have new insights into the animal's longevity - better-constructed proteins.

Proteins are involved in nearly all functions of an animal cell, and consequently, are essential to all organisms. But before proteins can do their job, they must fold into the appropriate shapes that allow them to connect to and interact with other structures in the cell.

In a paper published this week in the Proceedings of the National Academy of Sciences, Vera Gorbunova and Andrei Seluanov describe their discovery of the process in naked mole rats that leads to virtually perfect proteins.

"While this is basic research," said Gorbunova, "we hope our findings encourage further studies on better protein synthesis."

Their work focused on naked mole rat ribosomes - the site of protein creation in the animal's cells - and began by happenstance. The researchers were working with ribosome RNA (rRNA) when they made a discovery. After applying a dye to a sample, they studied it under ultraviolet light only to find three dark bands - representing concentrations of different rRNA molecules -not the two bands that are characteristic of all other animals, suggesting that there is a "hidden break" in the naked mole rat rRNA.

Since rRNA is an essential part of the protein-creation mechanism, the two biologists decided to see if the broken rRNA affects the quality of naked mole rat proteins.

Ribosome RNA strands act as scaffolds on the ribosome, a protein synthesis machine. Changing the shape of the scaffold can have a profound effect on the organization of the ribosome parts.

Gorbunova and Seluanov discovered that the naked mole rat's rRNA scaffold is indeed unique. The rRNA strands split at two specific locations and discard the intervening segment. Instead of floating off on their own, the two remaining pieces from each strand stay close to each other and act as a scaffold on which ribosomal proteins are assembled to create a functional ribosome—a molecular machine that puts amino acids together to create proteins. And the results are impressive.

When the ribosome connects amino acids together to create a protein a mistake is occasionally introduced when an incorrect amino acid is inserted. Gorbunova and Seluanov found that the proteins made by naked mole rat cells are up to 40 times less likely to contain such mistakes than the proteins made by mouse cells.

"This is important because proteins with no aberrations help the body to function more efficiently," said Seluanov.

The next step for the biologists is to split mouse rRNA in the same way to see if it would lead to improved protein creation.

The two biologists hope their work will eventually result in pharmaceutical treatments that modulate protein synthesis in humans, though any medical solution is a long way off.


Niacin, the fountain of youth for roundworms

The vitamin niacin has a life-prolonging effect, as Michael Ristow has demonstrated in roundworms. From his study, the ETH-Zurich professor also concludes that so-called reactive oxygen species are healthy, not only disagreeing with the general consensus, but also many of his peers.

Who would not want to live a long and healthy life? A freely available food supplement could help in this respect, scientists from ETH Zurich have demonstrated in roundworms. Vitamin B3 – also known as niacin – and its metabolite nicotinamide in the worms’ diet caused them to live for about one tenth longer than usual.

As an international team of researchers headed by Michael Ristow, a professor of energy metabolism, has now experimentally demonstrated, niacin and nicotinamide take effect by promoting formation of so-called free radicals. “In roundworms, these reactive oxygen species prolong life,” says Ristow.

 

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“No scientific evidence for usefulness of antioxidants”

This might seem surprising as reactive oxygen species are generally considered to be unhealthy. Ristow’s view also contradicts the textbook opinion championed by many other scientists. Reactive oxygen species are known to damage somatic cells, a condition referred to as oxidative stress. Particular substances, so-called antioxidants, which are also found in fruit, vegetables and certain vegetable oils, are capable of neutralising these free radicals. Many scientists believe that antioxidants are beneficial to health.

“The claim that intake of antioxidants, especially in tablet form, promotes any aspect of human health lacks scientific support,” says Ristow. He does not dispute that fruit and vegetables are healthy. However, this may rather be caused by other compounds contained therein, such as so-called polyphenols.

“Fruit and vegetables are healthy, despite the fact that they contain antioxidants,” says the ETH-Zurich professor. Based on the current and many previous findings he is convinced that small amounts of reactive oxygen species and the oxidative stress they trigger have a health-promoting impact. “Cells can cope well with oxidative stress and neutralise it,” says Ristow.

Substance mimics endurance sport

In earlier studies on humans, Ristow demonstrated that the health-enhancing effect of endurance sports is mediated via an increased formation of reactive oxygen species – and that antioxidants abolish this effect. Based on the present study, he concludes that niacin brings about a similar metabolic condition to exercise.

“Niacin tricks the body into believing that it is exercising – even when this is not the case,” says Ristow. Such compounds are known as “exercise mimetics”.

The researchers conducted their experiments on the model organism Caenorhabditis elegans. This worm, which is merely one millimetre in length, can be easily maintained and has a lifespan of only a month, making it the ideal model organism for ageing research.

Also relevant for humans

The results of the study may also be of relevance for humans, says Ristow. After all, the metabolic pathway initiated by niacin is very similar in roundworms and higher organisms. Whether niacin has similar effects on the life expectancy of mice is the subject of Ristow’s current research. Previous studies also suggest a health-enhancing effect of niacin in humans with elevated blood cholesterol levels.

Niacin and nicotinamide have been approved as dietary supplements for decades. Ristow could easily envisage the substances being used broadly for therapeutic purposes in the future. A whole series of foods naturally contain niacin, including meat, liver, fish, peanuts, mushrooms, rice and wheat bran. Whether nutritional uptake is sufficient for a health-enhancing or lifespan-extending effect, however, remains to be demonstrated, says Ristow.

Disputed impact of enzymes

The latest study on the effects of niacin and nicotinamide is based on a particular class of enzymes, the sirtuins, which convert niacin into nicotinamide. Moreover, they are also involved in gene regulation, helping to down regulate the activity of certain genes. Until today, scientists have been disputing whether sirtuins have a life-prolonging impact.

Ristow and his team’s work now suggests that the activity of sirtuins actually prolongs life in roundworms. According to the study, however, the life-prolonging effect is not down to gene regulation, as has often been supposed in the past. Instead, the effect is due to the conversion of niacin into nicotinamide.

Studying genetically modified roundworms that were unable to convert nicotinamide into certain other metabolic products, the scientists did not observe any lifespan extension, even after overexpression of sirtuins, which otherwise lead to an increased life expectancy.

 

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