Re: Klotho protein extends life in mice

[Guest guest]

Tony,

But doesn't the drosophila study that Rodney pointed us to the other

day indicate that limiting protein is more effective than limiting

carbohydrates in CR? Or is the klotho study more relevant to humans

because it occured in mice rather than flies? -- Diane

" Calories Do Not Explain Extension of Life Span by Dietary

Restriction in Drosophila "

Mair, D. W. Piper, and Partridge

" Dietary restriction (DR) extends life span in diverse organisms,

including mammals, and common mechanisms may be at work. DR is often

known as calorie restriction, because it has been suggested that

reduction of calories, rather than of particular nutrients in the

diet, mediates extension of life span in rodents. We here demonstrate

that extension of life span by DR in Drosophila is not attributable

to the reduction in calorie intake. Reduction of either dietary yeast

or sugar can reduce mortality and extend life span, but by an amount

that is unrelated to the calorie content of the food, and with yeast

having a much greater effect per calorie than does sugar. Calorie

intake is therefore not the key factor in the reduction of mortality

rate by DR in this species. "

--Diane

[Guest guest]

Tony,

But doesn't the drosophila study that Rodney pointed us to the other

day indicate that limiting protein is more effective than limiting

carbohydrates in CR? Or is the klotho study more relevant to humans

because it occured in mice rather than flies? -- Diane

" Calories Do Not Explain Extension of Life Span by Dietary

Restriction in Drosophila "

Mair, D. W. Piper, and Partridge

" Dietary restriction (DR) extends life span in diverse organisms,

including mammals, and common mechanisms may be at work. DR is often

known as calorie restriction, because it has been suggested that

reduction of calories, rather than of particular nutrients in the

diet, mediates extension of life span in rodents. We here demonstrate

that extension of life span by DR in Drosophila is not attributable

to the reduction in calorie intake. Reduction of either dietary yeast

or sugar can reduce mortality and extend life span, but by an amount

that is unrelated to the calorie content of the food, and with yeast

having a much greater effect per calorie than does sugar. Calorie

intake is therefore not the key factor in the reduction of mortality

rate by DR in this species. "

--Diane

[Guest guest]

Diane: we don't know what's relevant to humans. The article in today's WP makes it clear that jumping to conclusions is premature. To quote from the article: " It appears to play a role in .....people, but that doesn't necessarily mean it's going to be as straightforward to extend life span in people as it is in mice " .......

on 8/26/2005 11:51 AM, Diane Walter at dianepwalter@... wrote:

Tony,

But doesn't the drosophila study that Rodney pointed us to the other

day indicate that limiting protein is more effective than limiting

carbohydrates in CR? Or is the klotho study more relevant to humans

because it occured in mice rather than flies? -- Diane

[Guest guest]

Diane: we don't know what's relevant to humans. The article in today's WP makes it clear that jumping to conclusions is premature. To quote from the article: " It appears to play a role in .....people, but that doesn't necessarily mean it's going to be as straightforward to extend life span in people as it is in mice " .......

on 8/26/2005 11:51 AM, Diane Walter at dianepwalter@... wrote:

Tony,

But doesn't the drosophila study that Rodney pointed us to the other

day indicate that limiting protein is more effective than limiting

carbohydrates in CR? Or is the klotho study more relevant to humans

because it occured in mice rather than flies? -- Diane

[Guest guest]

Hi All,

Here is another description of the work from a more science-oriented source.

http://news.nationalgeographic.com/news/2005/08/0825_050825_aging.html

The pdf of the article is not available, but below is the Science editorial

description, the citation and abstract of the article.

PHYSIOLOGY:

Boosting Gene Extends Mouse Life Span

Couzin

Science 26 August 2005; 309: 1310-1311 [DOI: 10.1126/science.309.5739.1310a] (in

News of the Week)

A protein named after the Greek goddess who spins life's thread has joined the

short

list of ways to extend a mouse's natural life span. Whereas lab mice can live

about

2 years, mice engineered to overproduce this protein, called Klotho, have

celebrated

third birthdays, Makoto Kuro-o of the University of Texas Southwestern Medical

Center in Dallas and his colleagues report online in this week's Science Express

(www.sciencemag.org/cgi/content/abstract/1112766). The mutant rodents represent

a

rare case of a single gene substantially influencing life span in mammals.

" I'm not a dreamer; I don't think we're going to find a master control gene for

aging, " says Harry Dietz, a geneticist at s Hopkins University in Baltimore,

land, who studies Klotho's counterpart in humans. But, he says, " this is the

next best thing. We have found something that perhaps has the ability to make

old

age richer. "

But Kuro-o, who discovered the gene that encodes Klotho, worries that " too much

Klotho might not be very good. " The mice he created with extra Klotho look like

animals at risk of diabetes. There's also disagreement over how Klotho works.

Mice lacking Klotho die young, after developing arteriosclerosis and other

age-related conditions much earlier than normal (Science, 7 November 1997, p.

1013).

Still, many doubted that extra Klotho would lengthen life span. With a

short-lived

mutant, " you always have to worry that it's just sick, " says Kenyon, who

studies aging at the University of California, San Francisco.

Rare milestone. These mice, which overexpress the gene for Klotho, have

celebrated

their third birthdays.

CREDIT: H. KUROSU

So, Kuro-o, his postdoctoral fellows Hiroshi Kurosu and Masaya Yamamoto, and

colleagues at universities in the U.S. and Japan created mice overexpressing the

gene for Klotho. While Klotho is produced only in the kidney and brain, a

fragment

of it slips into the blood and may act like a hormone. Males making extra Klotho

lived up to 30% longer than normal males, and the mutant females survived 20%

longer

than normal counterparts. As with lab animals coaxed to have lengthy life spans,

the

altered rodents had fertility problems. They produced about half the expected

number

of offspring.

Males appeared more affected by Klotho than females did. Their blood, unlike

that of

females, contained more insulin than normal mice. This suggested that the male

mutants were somewhat resistant to insulin--a symptom, in extreme forms, of

diabetes. The Klotho-boosted males and females had normal glucose levels, a

surprise

because untreated diabetes causes high glucose. These features don't appear in

other

long-lived mice, which are usually insulin-sensitive and have low glucose.

Klotho's effects on insulin could connect the protein to a hot story in aging

research. Suppression of signaling by insulin and the related hormone

insulin-like

growth factor-1 (IGF-1) is one of the most consistently successful ways to

extend

life span in many species. Long-lived mice that are sensitive to insulin also

usually have dampened insulin and IGF-1 signaling.

In rat cells, Klotho inhibited insulin signaling, making it tough for the

hormone to

do its job. Kuro-o's group also showed that some mice lacking Klotho survived

somewhat longer and suffered fewer diseases when the team coaxed insulin and

IGF-1

signaling back to normal. Klotho " ties in beautifully " with the IGF-1 story,

says

, a gerontologist at the University of Washington in Seattle.

Others are less sure. The link is " tenuous, " says Luciano Rossetti, director of

the

diabetes research center at Albert Einstein College of Medicine in New York

City. He

points out that female mice with extra Klotho have normal insulin action but

live

substantially longer.

Kenyon says the new work raises the possibility that life span can be extended

alongside mild insulin resistance, a trait considered deleterious to longevity.

Researchers would now like to know if Klotho levels in humans correlate with

life

span--for example, if the blood of centenarians is swimming with it.

Suppression of Aging in Mice by the Hormone Klotho

Hiroshi Kurosu, Masaya Yamamoto, D. , Johanne V. Pastor, Animesh

Nandi,

Prem Gurnani, Owen P. McGuinness, Hirotaka Chikuda, Masayuki Yamaguchi, Hiroshi

Kawaguchi, Iichiro Shimomura, Yoshiharu Takayama, Joachim Herz, C. Kahn,

P. Rosenblatt, and Makoto Kuro-o

Published online 25 August 2005 [DOI: 10.1126/science.1112766] (in Science

Express

Research Articles)

A defect in Klotho gene expression in mice accelerates the degeneration of

multiple

age-sensitive traits. Here we show that overexpression of Klotho in mice extends

life span. Klotho protein functions as a circulating hormone that binds to a

cell-surface receptor and represses intracellular signals of insulin and

insulin-like growth factor-1 (IGF1), an evolutionarily conserved mechanism for

extending life span. Alleviation of aging-like phenotypes in Klotho-deficient

mice

was observed by perturbing insulin/IGF1 signaling, suggesting that

Klotho-mediated

inhibition of insulin/IGF1 signaling contributes to its anti-aging properties.

Klotho protein may function as an anti-aging hormone in mammals.

--- citpeks <citpeks@...> wrote:

> The Washington Post has a front-page story about a paper published

> on-line yesterday in the journal Science by Makoto Kuro-o of the

> University of Texas's Southwestern Medical Center at Dallas. The

> klotho protein is also found in humans and it modulates the

> insuling/IGF-1 pathway. This study seems to add more support for the

> theory that insulin accelerates aging.

>

> We normally argue about what ratios of protein, fat, and carbohydrates

> are OPTIMAL for longevity. The mounting evidence makes me wonder

> whether equicaloric low-carb diets may be better for life extension

> than high carb diets.

Al Pater, PhD; email: old542000@...

__________________________________________________

[Guest guest]

Hi All,

Here is another description of the work from a more science-oriented source.

http://news.nationalgeographic.com/news/2005/08/0825_050825_aging.html

The pdf of the article is not available, but below is the Science editorial

description, the citation and abstract of the article.

PHYSIOLOGY:

Boosting Gene Extends Mouse Life Span

Couzin

Science 26 August 2005; 309: 1310-1311 [DOI: 10.1126/science.309.5739.1310a] (in

News of the Week)

A protein named after the Greek goddess who spins life's thread has joined the

short

list of ways to extend a mouse's natural life span. Whereas lab mice can live

about

2 years, mice engineered to overproduce this protein, called Klotho, have

celebrated

third birthdays, Makoto Kuro-o of the University of Texas Southwestern Medical

Center in Dallas and his colleagues report online in this week's Science Express

(www.sciencemag.org/cgi/content/abstract/1112766). The mutant rodents represent

a

rare case of a single gene substantially influencing life span in mammals.

" I'm not a dreamer; I don't think we're going to find a master control gene for

aging, " says Harry Dietz, a geneticist at s Hopkins University in Baltimore,

land, who studies Klotho's counterpart in humans. But, he says, " this is the

next best thing. We have found something that perhaps has the ability to make

old

age richer. "

But Kuro-o, who discovered the gene that encodes Klotho, worries that " too much

Klotho might not be very good. " The mice he created with extra Klotho look like

animals at risk of diabetes. There's also disagreement over how Klotho works.

Mice lacking Klotho die young, after developing arteriosclerosis and other

age-related conditions much earlier than normal (Science, 7 November 1997, p.

1013).

Still, many doubted that extra Klotho would lengthen life span. With a

short-lived

mutant, " you always have to worry that it's just sick, " says Kenyon, who

studies aging at the University of California, San Francisco.

Rare milestone. These mice, which overexpress the gene for Klotho, have

celebrated

their third birthdays.

CREDIT: H. KUROSU

So, Kuro-o, his postdoctoral fellows Hiroshi Kurosu and Masaya Yamamoto, and

colleagues at universities in the U.S. and Japan created mice overexpressing the

gene for Klotho. While Klotho is produced only in the kidney and brain, a

fragment

of it slips into the blood and may act like a hormone. Males making extra Klotho

lived up to 30% longer than normal males, and the mutant females survived 20%

longer

than normal counterparts. As with lab animals coaxed to have lengthy life spans,

the

altered rodents had fertility problems. They produced about half the expected

number

of offspring.

Males appeared more affected by Klotho than females did. Their blood, unlike

that of

females, contained more insulin than normal mice. This suggested that the male

mutants were somewhat resistant to insulin--a symptom, in extreme forms, of

diabetes. The Klotho-boosted males and females had normal glucose levels, a

surprise

because untreated diabetes causes high glucose. These features don't appear in

other

long-lived mice, which are usually insulin-sensitive and have low glucose.

Klotho's effects on insulin could connect the protein to a hot story in aging

research. Suppression of signaling by insulin and the related hormone

insulin-like

growth factor-1 (IGF-1) is one of the most consistently successful ways to

extend

life span in many species. Long-lived mice that are sensitive to insulin also

usually have dampened insulin and IGF-1 signaling.

In rat cells, Klotho inhibited insulin signaling, making it tough for the

hormone to

do its job. Kuro-o's group also showed that some mice lacking Klotho survived

somewhat longer and suffered fewer diseases when the team coaxed insulin and

IGF-1

signaling back to normal. Klotho " ties in beautifully " with the IGF-1 story,

says

, a gerontologist at the University of Washington in Seattle.

Others are less sure. The link is " tenuous, " says Luciano Rossetti, director of

the

diabetes research center at Albert Einstein College of Medicine in New York

City. He

points out that female mice with extra Klotho have normal insulin action but

live

substantially longer.

Kenyon says the new work raises the possibility that life span can be extended

alongside mild insulin resistance, a trait considered deleterious to longevity.

Researchers would now like to know if Klotho levels in humans correlate with

life

span--for example, if the blood of centenarians is swimming with it.

Suppression of Aging in Mice by the Hormone Klotho

Hiroshi Kurosu, Masaya Yamamoto, D. , Johanne V. Pastor, Animesh

Nandi,

Prem Gurnani, Owen P. McGuinness, Hirotaka Chikuda, Masayuki Yamaguchi, Hiroshi

Kawaguchi, Iichiro Shimomura, Yoshiharu Takayama, Joachim Herz, C. Kahn,

P. Rosenblatt, and Makoto Kuro-o

Published online 25 August 2005 [DOI: 10.1126/science.1112766] (in Science

Express

Research Articles)

A defect in Klotho gene expression in mice accelerates the degeneration of

multiple

age-sensitive traits. Here we show that overexpression of Klotho in mice extends

life span. Klotho protein functions as a circulating hormone that binds to a

cell-surface receptor and represses intracellular signals of insulin and

insulin-like growth factor-1 (IGF1), an evolutionarily conserved mechanism for

extending life span. Alleviation of aging-like phenotypes in Klotho-deficient

mice

was observed by perturbing insulin/IGF1 signaling, suggesting that

Klotho-mediated

inhibition of insulin/IGF1 signaling contributes to its anti-aging properties.

Klotho protein may function as an anti-aging hormone in mammals.

--- citpeks <citpeks@...> wrote:

> The Washington Post has a front-page story about a paper published

> on-line yesterday in the journal Science by Makoto Kuro-o of the

> University of Texas's Southwestern Medical Center at Dallas. The

> klotho protein is also found in humans and it modulates the

> insuling/IGF-1 pathway. This study seems to add more support for the

> theory that insulin accelerates aging.

>

> We normally argue about what ratios of protein, fat, and carbohydrates

> are OPTIMAL for longevity. The mounting evidence makes me wonder

> whether equicaloric low-carb diets may be better for life extension

> than high carb diets.

Al Pater, PhD; email: old542000@...

__________________________________________________

[Guest guest]

I recall previously, DR was not quite what I thought of as CR.

Klotho is a gene perhaps associated with lifespan. I don't associate manipulating any lifespan gene with any change in my eating habits.

Limiting protein for humans should be based on health issues first. And whether I agree with them or not we do have req'ts for protein, which says CRONies need more at lower caloric intake. Like 20% more in Anti Aging plan pg53.

Regards.

[ ] Re: Klotho protein extends life in mice

Tony,But doesn't the drosophila study that Rodney pointed us to the otherday indicate that limiting protein is more effective than limitingcarbohydrates in CR? Or is the klotho study more relevant to humansbecause it occured in mice rather than flies? -- Diane"Calories Do Not Explain Extension of Life Span by DietaryRestriction in Drosophila" Mair, D. W. Piper, and Partridge"Dietary restriction (DR) extends life span in diverse organisms,including mammals, and common mechanisms may be at work. DR is oftenknown as calorie restriction, because it has been suggested thatreduction of calories, rather than of particular nutrients in thediet, mediates extension of life span in rodents. We here demonstratethat extension of life span by DR in Drosophila is not attributableto the reduction in calorie intake. Reduction of either dietary yeastor sugar can reduce mortality and extend life span, but by an amountthat is unrelated to the calorie content of the food, and with yeasthaving a much greater effect per calorie than does sugar. Calorieintake is therefore not the key factor in the reduction of mortalityrate by DR in this species."--Diane

[Guest guest]

I recall previously, DR was not quite what I thought of as CR.

Klotho is a gene perhaps associated with lifespan. I don't associate manipulating any lifespan gene with any change in my eating habits.

Limiting protein for humans should be based on health issues first. And whether I agree with them or not we do have req'ts for protein, which says CRONies need more at lower caloric intake. Like 20% more in Anti Aging plan pg53.

Regards.

[ ] Re: Klotho protein extends life in mice

Tony,But doesn't the drosophila study that Rodney pointed us to the otherday indicate that limiting protein is more effective than limitingcarbohydrates in CR? Or is the klotho study more relevant to humansbecause it occured in mice rather than flies? -- Diane"Calories Do Not Explain Extension of Life Span by DietaryRestriction in Drosophila" Mair, D. W. Piper, and Partridge"Dietary restriction (DR) extends life span in diverse organisms,including mammals, and common mechanisms may be at work. DR is oftenknown as calorie restriction, because it has been suggested thatreduction of calories, rather than of particular nutrients in thediet, mediates extension of life span in rodents. We here demonstratethat extension of life span by DR in Drosophila is not attributableto the reduction in calorie intake. Reduction of either dietary yeastor sugar can reduce mortality and extend life span, but by an amountthat is unrelated to the calorie content of the food, and with yeasthaving a much greater effect per calorie than does sugar. Calorieintake is therefore not the key factor in the reduction of mortalityrate by DR in this species."--Diane