7 replies to this topic

[kevin]

Link: http://www.eurekaler...u-boa060204.php

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Public release date: 2-Jun-2004

Contact: Wendy Lawton
Wendy_Lawton@brown.edu
401-863-1862
Brown University

Biology of aging
Insulin plays central role in aging, Brown scientists discover
PROVIDENCE, R.I. -- When the chemical messages sent by an insulin-like hormone are reduced inside the fat cells of the fruit fly, the fly's lifespan increases significantly, according to new research conducted at Brown University.

A similar phenomenon has already been observed in worms, according to Brown biology professor Marc Tatar. But never before, Tatar says, has it been seen in fruit flies – whose 13,601 genes are shared in many ways by humans.

The experiment, detailed in the current issue of Nature, also sheds important light on the role insulin plays in the regulation of its own synthesis.

Block the hormone's action inside a few specific cells, the study shows, and the entire body stays healthier longer. Scientists previously thought insulin triggered other hormones to achieve this effect, but Tatar and his team found that insulin regulates its own production and that it directly regulates tissue aging. The principle: Keep insulin levels low and cells are stronger, staving off infection and age-related diseases such as cancer, dementia and stroke.

"Think of the body like a car," Tatar says. "We knew insulin controlled the car's speed by regulating things like the gas pedal and the fuel injectors. Now we know that insulin is also the fuel that makes the engine go."

To conduct the experiment, Tatar and four other Brown researchers created a line of genetically altered flies which had dFOXO – a protein controlled by the fly equivalent of insulin – inserted into the genetic material of fat cells near their brains.

Some flies were fed mifepristone, a chemical copy of progesterone. This hormone activated a switch attached to dFOXO, which in turn repressed the normal insulin signals inside the cells. As a surprising result, insulin production was lowered throughout the body. These flies lived an average of 50 days – 18 days longer than flies whose insulin signals went unchecked.

"We now know that insulin is a direct player in the aging process," Tatar says. "So the research fits some key puzzle pieces together. And it should change the way we think about aging."

Tatar's research is part of a growing body of evidence linking low insulin levels to increased longevity. In recent years, scientists have found that mice and other animals live longer when they eat a low-calorie diet, which reduces insulin production.

"Aging regulation is a complex physiological process of nutritional inputs, metabolic regulation and hormone secretion," Tatar says. "But we still have so many unanswered questions." [but we're actually making some pretty awesome progress -KP]

Tatar and his team conducted their research over an 18-month period. The work was funded by the National Institutes of Health, the American Federation of Aging Research, the Ellison Medical Foundation and Pfizer Inc.


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[ocsrazor]

There is no doubt that there is a tremendous overabundance of carbs available in current Western diets and that stressing the insulin/glucagon system till it breaks is a major cause of system failures we see with aging as the paper has clearly shown, BUT....

the Atkins diet is also not particular healthy because of its insistence on putting people into ketosis, forcing the body to burn its own deep fat stores to produce a healthy level of glucose, which is particularly unhealthy for the nervous system which depends on a steady glucose supply and will cannibalize the lipid in myelin that insulates axons in order to get it during ketotic states. I would not suggest the Atkins diet to anyone for this reason, but as an alternative one of the lower carb, but not no or extremely low carb diets. Even so, rapid weight loss through dieting is never healthy, but a general change in eating towards balanced meals with lower amounts of processed carbs and gradually increased activity levels.

As a further comment on the paper, its nice to finally see a group prove what much of the aging field has suspected for a while, and that registered dieticians have often rejected. The old calories in/calories out story just won't fly anymore - the type of calories you are consuming is very important to your overall health.

Best,
Peter

[fruitimmortal]

I know 2 people that lived on the Atkins Diet for many weeks.
Not only did they loose some weight but also their mind.(just kidding)
Actually they became very aggressive and gittery; not to mention they suffered from bad breath.

All this Hype about Carbo hydrates, the body needs them if they are consumed in their uncooked state like in Fruits.

Carbs are needed for energy
Hydrates for the hydrating of the cells.


when Carb Foods are cooked, they loose their hydrating qualities since
heat causes the liquids to evaporate.

i read that when pigs are fed on cooked Potatoes they gain weight,
when fed raw potatoes no weightgain occurred.

recently i read that there is almost no insulin released when
consuming fruit ? [huh]

[Bruce Klein]

The danger of sustained ingestion of pure glucose/sucrose cannot be overemphasized. I would like to see warning labels of diabetes, obesity and heart disease on candy bars.

A good idea which may not be too far fetched.

[Cyto]

Fat cells could provide the key to a longer life

With the threat of an obesity crisis looming, a study led by UCL researchers reveals today that fat tissue isn't always the enemy. Reporting in the journal Science they show that a molecular signalling pathway in fat tissue is an important mediator in extending lifespan.

The study, conducted on one of scientists' favourite model organisms - the fruit fly - found that reducing activity of the insulin/insulin-like growth factor (IIS) signalling pathway in fat tissue of adults extended life by up to 50 per cent.

Previously it has been shown that reducing the activity of the IIS pathway extends lifespan in fruit flies, mice and the worm C. elegans. But the cellular processes that determine longevity were not understood.

Results suggest the system that governs longevity evolved in a precursor of all three species and is likely to be conserved in humans.

Professor Linda Partridge of UCL's Department of Biology, and senior author of the study, says:

"Basically, we are learning that nearly everything in biology is highly conserved. For years biologists studying ageing were convinced that it just happened and there wouldn't be genes that controlled it - you just wore out. But it became apparent independent of weight or size, some animals live much longer than others.

"Researchers became intrigued that on average a mouse lives for two years, a canary for 13 and a bat for 50 yet these species are all around the same size and warm blooded. A tortoise lives for up to one hundred years, but humans live for only 75. This suggests there must be a genetic determinant of the rate of ageing and these regulatory mechanisms can be set differently in different species. All we have to do is crack the code to reset the clock and our research takes this a step closer."

The possibility of extending life span has preoccupied scientists for many years. Leading theories include the idea that eating less slows down the progressive damage caused by free radicals that are released when oxygen is used to breakdown fats and carbohydrates. But another theory is that calorie restriction does something critical to the insulin-signalling pathway that helps regulate how glucose is used by the body.

Dr Maria Giannakou of UCL's Department of Biology, who led the study, explains:

"Studies in rats have shown restricting diet doubles lifespan but the pay off is reduced fertility. Elsewhere, groups have looked at mutations such as the DAF-2 gene in C. elegans, which can also double life span or reduce fertility depending on what stage in life the gene is interfered with.

"DAF-2 encodes the worms' equivalent of the human insulin receptor and as such form part of the IIS pathway. As animals on restricted diets are far less likely to get diabetes and related disorders, this suggests that genes involved in glucose metabolism might be linked to the genes involved in ageing."

Previous studies have shown reducing DAF-2 function during development affects only fertility, but in adulthood reducing function affects only lifespan. The researchers concluded that the two effects influenced different parts of the IIS pathway and their affects could be isolated.

Efforts focussed on a key target in the IIS pathway in the fruit fly, dFOXO. Known as a transcription factor, it helps activate and regulate genes.

They found that increasing levels of the transcription factor dFOXO in the fat cells of female fruit flies from the onset of adulthood increased lifespan by between 20 and 50 per cent and reduced fertility by 50 per cent. But no effect was observed in male flies.

"The functions of fruit fly fat include many of the metabolic activities of mammalian liver and fat storage. In mice deletion of insulin receptors in white fat cells results in a lean long living adult. Together this suggests that fat tissue is crucial in extending lifespan by altering the IIS pathway," said Dr Giannakou.

"Further work needs to be done to determine why there is a different affect in both sexes," added Professor Partridge.

"It could be because females are more influenced by food and its consequences. They make things – eggs, babies, and need a lot of nutrients for this. Males tend to move around a lot - to find females and persuade them to mate, and need less nutrients to make things. But this is just speculation."