Re: Re: the road to longevity: the molecular basis of lifespan becomes clearer

[Guest guest]

First what paper? The title may be associated with a series of articles.

Second - sounds like generalities, hypothesizing future stuff.

Third, the ROS is something we knew about 25 yrs ago and just now people are beginning to question the antioxidant applications.

There have been anti-aging chemicals, based on one very small bit of knowledge, but until we have the whole picture of the human genome, we won't know what they will actually do.

EG, we talk about idealistic things like balancing w-3/w-6 when in fact we don't know how, and the fats we eat overwhelm any thought of balancing those. IMO, the endocrine system acting as a result of a gene or maybe amplifying the gene is the key to whether we get fat on 3000 kcals or remain thin.

I thought it interesting my article noted calorie restriction known for 80 yrs, and we still have trouble applying it.

I'm still trying to draw a diagram of the PGs, etc. and their effects, and the data is ever so confusing.

Just an example, is IGF-1 good or bad? One place in sears book (pg 232 anti-aging zone), he says it builds muscle mass.

Regards

[ ] Re: the road to longevity: the molecular basis of lifespan becomes clearer

Jim,I looked up the referenced paper and found an entirely differentabstract-- one that made more sense in relation to the title of yourlast message than the abstract below it:Abstract:Objective: Although the quest for longevity is as old as civilizationitself, only recently have technical and conceptual advances ingenomics research brought us to the point of understanding the precisemolecular events that make us age. This heralds an era whenmanipulations of these will enable us to live longer, healthier lives.The present review describes how recent experimental strategies haveidentified key genes and intracellular pathways that are responsiblefor ageing and longevity.Findings: In diverse species transcription factors belonging to theforkhead/winged helix box gene, group O (FOXO) subfamily have beenfound to be crucial in downstream suppression of the life-shorteningeffects of insulin/insulin-like growth factor-I receptor signallingpathways that, when upregulated, accelerate ageing by suppression ofFOXO. The various adverse processes activated upon FOXO suppressioninclude increased generation of reactive oxygen species (ROS). ROS arepivotal for the onset of various common conditions, includinghypertension, atherosclerosis, type 2 diabetes, cancer and Alzheimer'sdisease, each of which shortens lifespan. In humans, FOXO3a, as wellas FOXO1 and -4, and their downstream effectors, could hold the key tocounteracting ageing and common diseases. An understanding of theprocesses controlled by these FOXOs should permit development of novelclasses of agents that will more directly counteract or prevent thedamage associated with diverse life-threatening conditions, and sofoster a life of good health to a ripe old age. Just like caloricrestriction, lifespan can be increased in various species byplant-derived polyphenols, such as resveratrol, via activation ofsirtuins in cells. Sirtuins, such as SIRT1 in mammals, utilize FOXOand other pathways to achieve their beneficial effects on health andlifespan.Conclusion: Lifespan is tractable and basic mechanisms are now known.Longevity research complements and overlaps research in most majormedical disciplines. Current progress bodes well for anever-increasing length of healthy life for those who adapt emergingknowledge personally (so-called 'longevitarians').--- In , "jwwright" <jwwright@e...>wrote:> Re: [ ] Dairy, Calcium helps fat lossJournal ofHypertension. 23(7):1285-1309, July 2005. > A forkhead in the road to longevity: the molecular basis of lifespanbecomes clearer> [Reviews]> , J> > Diet and lifestyle> For just about all common diseases, be they cardiovascular,oncological or neurological, the messages on prevention, and thuspostponement of death, are remarkably similar - don't smoke, don'tdrink alcohol, get plenty of exercise, meditate, reduce calories aswell as sodium chloride, animal fats, trans fatty acids and proteins,consume low glycaemic index foods [16,17], have 6-9 servings ofvegetables and fruit per day, including soya products, whole grainsand nuts, and consume 'good oils' such olive oil and omega-3 fattyacids in cold-water fish [18,19]. In the case of alcohol, although aJ-shaped relationship has been found for cardiovascular disease, thebenefits apply mostly to middle-aged people with high cholesterolindicative of a poor diet and lifestyle, but for cancer risk there isno threshold below which risk is absent [20].> > Caloric restriction> It has been known for 80 years that enormous increases in lifespancan be achieved in laboratory animals by restricting caloric intake by30-40%, while maintaining adequate nutrient intake [31-34]. In 25% ofrats autopsy has, moreover, failed to reveal the cause of death.Limiting growth during just the postnatal period of suckling increaseslifespan and protects against an obesity-inducing diet later in life,whereas reduced growth in utero followed by catch-up growthpostnatally shortens lifespan, particularly when a cafeteria-stylediet is provided from day 21 [35]. In human terms, these datarepresent the difference between living to age 50 or age 75.> > Caloric restriction reduces protein synthesis in liver and skeletalmuscle, as well as the load of oxidized proteins [36], owing to fasterturnover and thus decreased metabolic toxin exposure [37]. Immunefunction is enhanced and inflammatory responses of ageing areinhibited [37]. As well, cancer is reduced, accompanied by increasedapoptosis ('programmed cell death') [37]. Lack of obesity alsocontributes.> > The first human experiment was in the 16th century when LuigiCornaro, at age 40, deliberately restricted his food intake for healthreasons and lived to 102 [40]. More recently human volunteers sealedinside Biosphere 2 for 2 years had to produce their own food, becamecalorically restricted, and their physiological and biochemicalparameters changed to resemble those of food-restricted monkeys andrats [41].

[Guest guest]

First what paper? The title may be associated with a series of articles.

Second - sounds like generalities, hypothesizing future stuff.

Third, the ROS is something we knew about 25 yrs ago and just now people are beginning to question the antioxidant applications.

There have been anti-aging chemicals, based on one very small bit of knowledge, but until we have the whole picture of the human genome, we won't know what they will actually do.

EG, we talk about idealistic things like balancing w-3/w-6 when in fact we don't know how, and the fats we eat overwhelm any thought of balancing those. IMO, the endocrine system acting as a result of a gene or maybe amplifying the gene is the key to whether we get fat on 3000 kcals or remain thin.

I thought it interesting my article noted calorie restriction known for 80 yrs, and we still have trouble applying it.

I'm still trying to draw a diagram of the PGs, etc. and their effects, and the data is ever so confusing.

Just an example, is IGF-1 good or bad? One place in sears book (pg 232 anti-aging zone), he says it builds muscle mass.

Regards

[ ] Re: the road to longevity: the molecular basis of lifespan becomes clearer

Jim,I looked up the referenced paper and found an entirely differentabstract-- one that made more sense in relation to the title of yourlast message than the abstract below it:Abstract:Objective: Although the quest for longevity is as old as civilizationitself, only recently have technical and conceptual advances ingenomics research brought us to the point of understanding the precisemolecular events that make us age. This heralds an era whenmanipulations of these will enable us to live longer, healthier lives.The present review describes how recent experimental strategies haveidentified key genes and intracellular pathways that are responsiblefor ageing and longevity.Findings: In diverse species transcription factors belonging to theforkhead/winged helix box gene, group O (FOXO) subfamily have beenfound to be crucial in downstream suppression of the life-shorteningeffects of insulin/insulin-like growth factor-I receptor signallingpathways that, when upregulated, accelerate ageing by suppression ofFOXO. The various adverse processes activated upon FOXO suppressioninclude increased generation of reactive oxygen species (ROS). ROS arepivotal for the onset of various common conditions, includinghypertension, atherosclerosis, type 2 diabetes, cancer and Alzheimer'sdisease, each of which shortens lifespan. In humans, FOXO3a, as wellas FOXO1 and -4, and their downstream effectors, could hold the key tocounteracting ageing and common diseases. An understanding of theprocesses controlled by these FOXOs should permit development of novelclasses of agents that will more directly counteract or prevent thedamage associated with diverse life-threatening conditions, and sofoster a life of good health to a ripe old age. Just like caloricrestriction, lifespan can be increased in various species byplant-derived polyphenols, such as resveratrol, via activation ofsirtuins in cells. Sirtuins, such as SIRT1 in mammals, utilize FOXOand other pathways to achieve their beneficial effects on health andlifespan.Conclusion: Lifespan is tractable and basic mechanisms are now known.Longevity research complements and overlaps research in most majormedical disciplines. Current progress bodes well for anever-increasing length of healthy life for those who adapt emergingknowledge personally (so-called 'longevitarians').--- In , "jwwright" <jwwright@e...>wrote:> Re: [ ] Dairy, Calcium helps fat lossJournal ofHypertension. 23(7):1285-1309, July 2005. > A forkhead in the road to longevity: the molecular basis of lifespanbecomes clearer> [Reviews]> , J> > Diet and lifestyle> For just about all common diseases, be they cardiovascular,oncological or neurological, the messages on prevention, and thuspostponement of death, are remarkably similar - don't smoke, don'tdrink alcohol, get plenty of exercise, meditate, reduce calories aswell as sodium chloride, animal fats, trans fatty acids and proteins,consume low glycaemic index foods [16,17], have 6-9 servings ofvegetables and fruit per day, including soya products, whole grainsand nuts, and consume 'good oils' such olive oil and omega-3 fattyacids in cold-water fish [18,19]. In the case of alcohol, although aJ-shaped relationship has been found for cardiovascular disease, thebenefits apply mostly to middle-aged people with high cholesterolindicative of a poor diet and lifestyle, but for cancer risk there isno threshold below which risk is absent [20].> > Caloric restriction> It has been known for 80 years that enormous increases in lifespancan be achieved in laboratory animals by restricting caloric intake by30-40%, while maintaining adequate nutrient intake [31-34]. In 25% ofrats autopsy has, moreover, failed to reveal the cause of death.Limiting growth during just the postnatal period of suckling increaseslifespan and protects against an obesity-inducing diet later in life,whereas reduced growth in utero followed by catch-up growthpostnatally shortens lifespan, particularly when a cafeteria-stylediet is provided from day 21 [35]. In human terms, these datarepresent the difference between living to age 50 or age 75.> > Caloric restriction reduces protein synthesis in liver and skeletalmuscle, as well as the load of oxidized proteins [36], owing to fasterturnover and thus decreased metabolic toxin exposure [37]. Immunefunction is enhanced and inflammatory responses of ageing areinhibited [37]. As well, cancer is reduced, accompanied by increasedapoptosis ('programmed cell death') [37]. Lack of obesity alsocontributes.> > The first human experiment was in the 16th century when LuigiCornaro, at age 40, deliberately restricted his food intake for healthreasons and lived to 102 [40]. More recently human volunteers sealedinside Biosphere 2 for 2 years had to produce their own food, becamecalorically restricted, and their physiological and biochemicalparameters changed to resemble those of food-restricted monkeys andrats [41].

[Guest guest]

That was yesterday.

My post was from the text, not from the abstract, so it could be same article. But I admit it doesn't sound like it.

Notice J Hypertens. 2005 Jul;23(7):1285-309. (your abstract - which I never read)

is not J Hypertens. 2005 Jul;23(7):1285-1309. (my post - not from Medline)

I don't know - maybe something crossfiled in the computers - can't get to them today.

Regards.

[ ] Re: the road to longevity: the molecular basis of lifespan becomes clearer

I was responding to a message you had sent out with that title, butthat had an inconsistent summary along with it: message #20276> > Re: [ ] Dairy, Calcium helps fat loss Journal of Hypertension. 23(7):1285-1309, July 2005. > > A forkhead in the road to longevity: the molecular basis of lifespan> becomes clearer> > [Reviews]> > , J> > > > Diet and lifestyle> > For just about all common diseases, be they cardiovascular,> oncological or neurological, the messages on prevention, and thus> postponement of death, are remarkably similar - don't smoke, don't> drink alcohol, get plenty of exercise, meditate, reduce calories as> well as sodium chloride, animal fats, trans fatty acids and proteins,> consume low glycaemic index foods [16,17], have 6-9 servings of> vegetables and fruit per day, including soya products, whole grains> and nuts, and consume 'good oils' such olive oil and omega-3 fatty> acids in cold-water fish [18,19]. In the case of alcohol, although a> J-shaped relationship has been found for cardiovascular disease, the> benefits apply mostly to middle-aged people with high cholesterol> indicative of a poor diet and lifestyle, but for cancer risk there is> no threshold below which risk is absent [20].> > > > Caloric restriction> > It has been known for 80 years that enormous increases in lifespan> can be achieved in laboratory animals by restricting caloric intake by> 30-40%, while maintaining adequate nutrient intake [31-34]. In 25% of> rats autopsy has, moreover, failed to reveal the cause of death.> Limiting growth during just the postnatal period of suckling increases> lifespan and protects against an obesity-inducing diet later in life,> whereas reduced growth in utero followed by catch-up growth> postnatally shortens lifespan, particularly when a cafeteria-style> diet is provided from day 21 [35]. In human terms, these data> represent the difference between living to age 50 or age 75.> > > > Caloric restriction reduces protein synthesis in liver and skeletal> muscle, as well as the load of oxidized proteins [36], owing to faster> turnover and thus decreased metabolic toxin exposure [37]. Immune> function is enhanced and inflammatory responses of ageing are> inhibited [37]. As well, cancer is reduced, accompanied by increased> apoptosis ('programmed cell death') [37]. Lack of obesity also> contributes.> > > > The first human experiment was in the 16th century when Luigi> Cornaro, at age 40, deliberately restricted his food intake for health> reasons and lived to 102 [40]. More recently human volunteers sealed> inside Biosphere 2 for 2 years had to produce their own food, became> calorically restricted, and their physiological and biochemical> parameters changed to resemble those of food-restricted monkeys and> rats [41].> > > >

[Guest guest]

That was yesterday.

My post was from the text, not from the abstract, so it could be same article. But I admit it doesn't sound like it.

Notice J Hypertens. 2005 Jul;23(7):1285-309. (your abstract - which I never read)

is not J Hypertens. 2005 Jul;23(7):1285-1309. (my post - not from Medline)

I don't know - maybe something crossfiled in the computers - can't get to them today.

Regards.

[ ] Re: the road to longevity: the molecular basis of lifespan becomes clearer

I was responding to a message you had sent out with that title, butthat had an inconsistent summary along with it: message #20276> > Re: [ ] Dairy, Calcium helps fat loss Journal of Hypertension. 23(7):1285-1309, July 2005. > > A forkhead in the road to longevity: the molecular basis of lifespan> becomes clearer> > [Reviews]> > , J> > > > Diet and lifestyle> > For just about all common diseases, be they cardiovascular,> oncological or neurological, the messages on prevention, and thus> postponement of death, are remarkably similar - don't smoke, don't> drink alcohol, get plenty of exercise, meditate, reduce calories as> well as sodium chloride, animal fats, trans fatty acids and proteins,> consume low glycaemic index foods [16,17], have 6-9 servings of> vegetables and fruit per day, including soya products, whole grains> and nuts, and consume 'good oils' such olive oil and omega-3 fatty> acids in cold-water fish [18,19]. In the case of alcohol, although a> J-shaped relationship has been found for cardiovascular disease, the> benefits apply mostly to middle-aged people with high cholesterol> indicative of a poor diet and lifestyle, but for cancer risk there is> no threshold below which risk is absent [20].> > > > Caloric restriction> > It has been known for 80 years that enormous increases in lifespan> can be achieved in laboratory animals by restricting caloric intake by> 30-40%, while maintaining adequate nutrient intake [31-34]. In 25% of> rats autopsy has, moreover, failed to reveal the cause of death.> Limiting growth during just the postnatal period of suckling increases> lifespan and protects against an obesity-inducing diet later in life,> whereas reduced growth in utero followed by catch-up growth> postnatally shortens lifespan, particularly when a cafeteria-style> diet is provided from day 21 [35]. In human terms, these data> represent the difference between living to age 50 or age 75.> > > > Caloric restriction reduces protein synthesis in liver and skeletal> muscle, as well as the load of oxidized proteins [36], owing to faster> turnover and thus decreased metabolic toxin exposure [37]. Immune> function is enhanced and inflammatory responses of ageing are> inhibited [37]. As well, cancer is reduced, accompanied by increased> apoptosis ('programmed cell death') [37]. Lack of obesity also> contributes.> > > > The first human experiment was in the 16th century when Luigi> Cornaro, at age 40, deliberately restricted his food intake for health> reasons and lived to 102 [40]. More recently human volunteers sealed> inside Biosphere 2 for 2 years had to produce their own food, became> calorically restricted, and their physiological and biochemical> parameters changed to resemble those of food-restricted monkeys and> rats [41].> > > >

[Guest guest]

I admit not reading the whole thing. On what basis were these " assertions " (as you call them below) made?

on 8/15/2005 12:11 PM, Rodney at perspect1111@... wrote:

Hi folks:

Having read the article posted by JW, " A Forkhead in the Road to

Longevity ............ " - at least up to the point where a heavy

fog of biochemistry started to shroud (for me at least) the content -

I found quite a few either very interesting or very surprising

assertions. I will list a few of them below and ask whether everyone

here agrees with them. Are they accurate?

1. Average future lifetime health costs for the average american at

age 70 is: $150,000. This number is lower for healthier people

despite the fact they live longer. (Interesting).

2. Genetics contributes only 25% of human lifespan variation. But

it contributes 50% of cognitive function in old age. (Interesting).

3. Included among the general factors known to increase lifespan

is: reduction in protein intake. (WHERE HAVE I BEEN ALL THIS TIME

NOT KNOWING THIS????)

4. " The principal dietary atherogen is milk protein beta-casein

A1. Its effect is three times stronge than smoking " (I FELL OFF MY

CHAIR READING THIS).

5. Ginkgo biloba may be beneficial. (OK!)

6. NSAIDs can reduce incidence of alzheimer's by 80% as well as

cancer risk. (80%? WOW)

7. Caloric restriction should only increase human lifespan

slightly. (Believable).

8. (In mice) giving insulin can reverse the effect of caloric

restriction on mitochondrial function. (So insulin is THAT bad?)

No doubt if I had the smarts I would have detected additional

astonishing assertions in that paper.

Has everyone else here, except me, known all these things listed

above all along?

Are they all really true????

Rodney.

[Guest guest]

I admit not reading the whole thing. On what basis were these " assertions " (as you call them below) made?

on 8/15/2005 12:11 PM, Rodney at perspect1111@... wrote:

Hi folks:

Having read the article posted by JW, " A Forkhead in the Road to

Longevity ............ " - at least up to the point where a heavy

fog of biochemistry started to shroud (for me at least) the content -

I found quite a few either very interesting or very surprising

assertions. I will list a few of them below and ask whether everyone

here agrees with them. Are they accurate?

1. Average future lifetime health costs for the average american at

age 70 is: $150,000. This number is lower for healthier people

despite the fact they live longer. (Interesting).

2. Genetics contributes only 25% of human lifespan variation. But

it contributes 50% of cognitive function in old age. (Interesting).

3. Included among the general factors known to increase lifespan

is: reduction in protein intake. (WHERE HAVE I BEEN ALL THIS TIME

NOT KNOWING THIS????)

4. " The principal dietary atherogen is milk protein beta-casein

A1. Its effect is three times stronge than smoking " (I FELL OFF MY

CHAIR READING THIS).

5. Ginkgo biloba may be beneficial. (OK!)

6. NSAIDs can reduce incidence of alzheimer's by 80% as well as

cancer risk. (80%? WOW)

7. Caloric restriction should only increase human lifespan

slightly. (Believable).

8. (In mice) giving insulin can reverse the effect of caloric

restriction on mitochondrial function. (So insulin is THAT bad?)

No doubt if I had the smarts I would have detected additional

astonishing assertions in that paper.

Has everyone else here, except me, known all these things listed

above all along?

Are they all really true????

Rodney.