Re: Popular Misconceptions about CR Lifestyle

[Guest guest]

Warren writes:

> The best CR-way to be is this: to eat very little and to put

> on weight very rapidly, even if you consume very few calories.

As you surmise, it's probably best not to exercise TOO

much. Keep in mind, though, that other things being

equal (esp. exercise), it would appear that the " burner "

rodents lived longer ;-D than those with the slowest

or most efficient metabolisms/mitochondria. On the

other hand, other things being equal, the fattest CR'd

rodents, as compared to the skinniest, may have lived

the longest in other studies IIRC. Sorry for

speaking generally and in code without reference links

~ it's a busy day at the office. Supplemental

comments/clarifications to my " lazy-man's " post, or,

as we lawyers might say, to my " issue spotting " post,

are welcome ;0)

Kenton

PS. Hi everyone. I'm Kenton, aka the " reckless

poster. " If anything said is off, it's not the devil that

made me do it...no sir no such antiquated copout for

me; rather, clearly, it's my lunch-skipping,

glucose-deprived, CR'd brain that made me do it ;-D

[Guest guest]

Have you seen this study Warren?

Extended longevity in mice lacking the insulin receptor in adipose

tissue

(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=12543978)

The abstract concludes:

Thus, a reduction of fat mass without caloric restriction can be

associated with increased longevity in mice, possibly through

effects on insulin signaling.

Not only was average life span increased so was maximum life span.

Regards,

> >

> > ... [because of my large amounts of exercise] I can eat

> > late at night, eat large amounts and still do not gain,

> > and am losing small amounts of weight...

>

> The best CR-way to be is this: to eat very little and to put

> on weight very rapidly, even if you consume very few calories.

>

> Then to stay low in weight, you must eat very little, and you

> are consuming the fewest calories possible, which is the origin

> of CR benefits.

>

> Eating lots of food (and calories) and failing to put on weight

> is the opposite of CR, but rather the public misconception and

> media platitude of " healthful diet and exercise " .

>

> -- Warren

[Guest guest]

Hi All,

What about:

mice with a fat-specific insulin receptor knockout (FIRKO).

Messed up mice may be irrelevant for such studies of longevity.

Cheers, Al Pater.

> > >

> > > ... [because of my large amounts of exercise] I can eat

> > > late at night, eat large amounts and still do not gain,

> > > and am losing small amounts of weight...

> >

> > The best CR-way to be is this: to eat very little and to put

> > on weight very rapidly, even if you consume very few calories.

> >

> > Then to stay low in weight, you must eat very little, and you

> > are consuming the fewest calories possible, which is the origin

> > of CR benefits.

> >

> > Eating lots of food (and calories) and failing to put on weight

> > is the opposite of CR, but rather the public misconception and

> > media platitude of " healthful diet and exercise " .

> >

> > -- Warren

[Guest guest]

Hi Al,

Knockouts allow researchers to find out the function of a protein by

removing it (knocking it out) from the gene. This allows them to

better study the mechanisms of ageing and why CR works to increase

longevity.

From another paper by members of the Joslin Diabetes Center and

Department of Medicine at Harvard Medical School:

Adipose tissue selective insulin receptor knockout protects against

obesity and obesity-related glucose intolerance.

(http://www.developmentalcell.com/content/article/abstract?

uid=PIIS1534580702001995)

ABstract: Insulin signaling in adipose tissue plays an important

role in lipid storage and regulation of glucose homeostasis. Using

the Cre-loxP system, we created mice with fat-specific disruption of

the insulin receptor gene (FIRKO mice). These mice have low fat

mass, loss of the normal relationship between plasma leptin and body

weight, and are protected against age-related and hypothalamic

lesion-induced obesity, and obesity-related glucose intolerance.

From the European Journal of Endocrinology (May 2003, Volume 148,

Issue 5)

http://www.eje.org/eje/148/5/default.htm

Prolonged life-span by defective insulin signalling?

Abstract: Increasing the individual life-span of a living being not

only has been the urgent longing of mankind throughout its history

but has become one interesting focus of research in the last couple

of years. Various genetic factors have been identified to be linked

with the phenomenon of longevity. From an endocrinological point of

view, however, the role of IGF-I in regulating life-expectancy has

been closely investigated recently. In the nematode C. elegans and

in the fruit fly Drosophila melanogaster loss of function mutations

in the IGF-I signalling pathway prolong life expectancy by 50% and

more. In contrast, activating mutations in insulin and IGF-I

signalling reverse the increment in life-span. In rodents, loss of

function mutations in the transcription factors Pit1 and Prop1 lead

to combined pituitary deficiencies and, among other hormone

deficiencies, reduced insulin and IGF-I serum concentrations.

Interestingly, despite the substantial dysregulation of the

endocrine environment, mice with Pit1 or Prop1 mutations have a

longer life expectancy than non- affected littermates.

So the mice are are quite relevent to the study of longevity.

Cheers,

> > > >

> > > > ... [because of my large amounts of exercise] I can eat

> > > > late at night, eat large amounts and still do not gain,

> > > > and am losing small amounts of weight...

> > >

> > > The best CR-way to be is this: to eat very little and to put

> > > on weight very rapidly, even if you consume very few calories.

> > >

> > > Then to stay low in weight, you must eat very little, and you

> > > are consuming the fewest calories possible, which is the

origin

> > > of CR benefits.

> > >

> > > Eating lots of food (and calories) and failing to put on weight

> > > is the opposite of CR, but rather the public misconception and

> > > media platitude of " healthful diet and exercise " .

> > >

> > > -- Warren

[Guest guest]

Hi All and ,

Rodent mutants have reduced life spans. When even with the

treatments, they do not live as long as normal, well-fat rodents.

Therefore, findings are typically meaningless for animals incuding

people.

Cheers, Al Pater.

> > > Have you seen this study Warren?

> > >

> > > Extended longevity in mice lacking the insulin receptor in

> adipose

> > > tissue

> > > (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

> > > cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=12543978)

> > >

> > > The abstract concludes:

> > >

> > > Thus, a reduction of fat mass without caloric restriction can

> be

> > > associated with increased longevity in mice, possibly through

> > > effects on insulin signaling.

> > >

> > > Not only was average life span increased so was maximum life

> span.

[Guest guest]

Hi Al,

The longevity of the knockout mice was increased.

> > > > Have you seen this study Warren?

> > > >

> > > > Extended longevity in mice lacking the insulin receptor in

> > adipose

> > > > tissue

> > > > (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

> > > > cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=12543978)

> > > >

> > > > The abstract concludes:

> > > >

> > > > Thus, a reduction of fat mass without caloric restriction

can

> > be

> > > > associated with increased longevity in mice, possibly

through

> > > > effects on insulin signaling.

> > > >

> > > > Not only was average life span increased so was maximum life

> > span.

[Guest guest]

Hi All,

But not as long as normal rodents did the mutants live. Such animals

are meaningless for examining longevity. They are only fixing things

that normally do not occur - early death due to bizzare mutations.

Cheers, Al Pater

> > > > > Have you seen this study Warren?

> > > > >

> > > > > Extended longevity in mice lacking the insulin receptor in

> > > adipose

> > > > > tissue

> > > > > (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

> > > > > cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=12543978)

> > > > >

> > > > > The abstract concludes:

> > > > >

> > > > > Thus, a reduction of fat mass without caloric restriction

> can

> > > be

> > > > > associated with increased longevity in mice, possibly

> through

> > > > > effects on insulin signaling.

> > > > >

> > > > > Not only was average life span increased so was maximum

life

> > > span.

[Guest guest]

Messed up mice may be irrelevant for such studies of longevity.

>

> Cheers, Al Pater.

The " Developmental Cell " study is NOT about testing to see if

altered mice's maximum life span was extended per se, but

elucidating various genetic mechanisms. This is highly relevant in

leading to a possible answer to the question why and how CRON works.

Modulating insulin and blood sugar is one of the competing strong

key theories of CRON efficacy, if not a serious piece of the puzzle.

Thanks.

Here's another study on IGF–insulin and longevity. Highlight: " this

pathway confers not only extended life spans but also increased

resistance to oxidative stress. " Wow, such a deal, two for the price

of one!

Trends in Endocrinology and Metabolism

Full A-Z Journal List Vol. 15, No. 4, May 2004 Full Text Record

Hormonal regulation of aging and life span

Holly M. Brown-Borg brownbrg@...

Trends in Endocrinology and Metabolism 2003, 14:151-153

Department of Pharmacology, Physiology and Therapeutics, University

of North Dakota, School of Medicine and Health Sciences, Grand

Forks, ND 58203, USA

Text only, PDF

Publications by

Holly M. Brown-Borg

Jump to this record in Evaluated MEDLINE

Related records from Evaluated MEDLINE

Related fulltext articles on BioMedNet

Fulltext articles on BioMedNet that cite this article

Abstract

GH–IGF–insulin and longevity

IGF-I receptor knockdown mice

Discussion

Conclusions

References

Copyright

A regulatory growth factor pathway has been implicated in

determination of longevity in a variety of species. Altered

signaling in this pathway confers not only extended life spans but

also increased resistance to oxidative stress. A new report using

mice engineered to express fewer receptors for insulin-like growth

factor (IGF-I), therefore reducing the signaling through this

pathway, provides strong supporting evidence that IGF-I signaling

does play a significant role in longevity. The IGF-I receptor

knockdown mice were fertile, slightly smaller and resisted oxidative

stressors more effectively when compared with normal littermate

mice. This, along with other recent evidence, could provide clues

towards potential therapeutic intervention to extend life span in

humans.

Identifying factors that affect longevity in experimental model

systems could provide significant insight into human aging. Over the

past few years, one group of closely related molecules continues to

surface in the biogerontology literature. The growth hormone (GH)–

insulin-like growth factor (IGF)–insulin family and corresponding

downstream signaling factors have been positively linked to life

span in a variety of species. An important contribution to this

field was recently published by Holzenberger and co-workers [1].

GH–IGF–insulin and longevity

Decreased levels of GH, IGF-I, insulin or downstream signaling

molecules in mammals, fruit flies, nematodes and yeast have been

shown to extend life span significantly [2–8] . Dwarf mice (Ames,

Snell and Laron) live significantly longer than normal littermate

mice [2–4] . Ames dwarf (df/df) and Snell dwarf (dw/dw) mice have

severely decreased plasma levels of GH as a consequence of mutations

in prop1 and pit1 genes, which ultimately result in decreased

circulating IGF-I and insulin levels and decreased activity of the

insulin–IGF-I signaling cascade. Laron dwarf mice (which lack the GH

receptor/binding protein gene) have high plasma GH levels, but GH

signaling is impaired, resulting in very low plasma IGF-I levels.

Similar components of the GH–insulin–IGF-I signaling pathway appear

to be longevity determinants in nematodes (Caenorhabditis elegans,

DAF-2), fruit flies (Drosophila melanogaster, chico; INR) and yeast

(Sch9) [5–8] . The DAF-2 mutants live significantly longer than do

wild-type worms when the mutant gene is expressed throughout life,

or when restricted to adulthood, or expressed exclusively in motor

neurons [7,9,10] . Likewise, mutant flies expressing altered

substrates (chico) or receptors for IGF-I-like genes (INR) outlive

normal flies. In addition to the significant life-span extension,

similarities among these experimental models include small body

size, hypofertility, altered metabolism and increased resistance to

oxidative stress.

The ability to counter oxidants more effectively is a hallmark of GH–

insulin–IGF-I longevity mutants. In fact, if one subscribes to the

free radical theory of aging, then the increase in antioxidant

defense and reduced oxidative tissue damage reported in the GH–

insulin–IGF-I mutants fits perfectly with this theory. Very few

studies have looked at specific effects of these hormones on the

generation of free radicals or expression of enzymes involved in the

removal of free radicals. Administration of GH or IGF-I both in

vitro and in vivo significantly suppresses catalase and glutathione

peroxidase enzymes, two of the key players in antioxidative defense

[11]. Dwarf mice (Ames, Snell and Laron), DAF-2 mutant worms and INR

mutant flies all share an increased ability to resist oxidative

stress, expressing increased antioxidative defenses with resultant

decreased oxidative damage in tissues when compared to wild type

controls.

Mice overexpressing GH (i.e. supraphysiological plasma levels)

exhibit a 50% reduction in life span, significantly reduced levels

of antioxidative defense molecules and increased oxidative damage to

cellular constituents [12]. Significant indicators of premature

aging observed include glomerulosclerosis, reduced replicative

potential, increased expression of GFAP, reduced neurotransmitter

turnover, early loss of reproductive competence and exacerbated age-

related declines in cognitive function (learning and memory).

IGF-I receptor knockdown mice

Holzenberger and co-workers [1] used the Cre-Lox technique to

determine the role of the IGF-I receptor in mammals. Mice expressing

zero copies (null; -/-) of the gene were not viable, as has been

shown previously. However, heterozygous expression (one copy of

normal gene; +/-) resulted in viable pups expressing half the number

of IGF-I receptors in several tissues. These animals exhibited

identical growth patterns to wild-type (normal; +/+) pups until

weaning (20 days), at which time growth rate declined resulting in

slightly smaller mice than littermate controls (males: -8%, P<0.05;

females: -6%, NS).

Importantly, partial expression of the IGF-I receptor resulted in a

significant extension of life span (26%). The IGF-I receptor

heterozygous knockout mice lived three (males) to six (females)

months longer than did normal mice (~19 months, both sexes). Longer

life spans in females over males is a commonly reported observation

[2–5,7] . In addition to the extended life span and small changes in

body weight, IGF-I receptor-knockdown mice exhibit increased serum

IGF-I levels, as a result of suboptimal tissue responsiveness to IGF-

I. Fasting blood glucose levels were normal, whereas non-fasting

(fed) levels in mutant males were 12% higher than in normal males.

In females, no significant differences in fed blood glucose were

observed. Similarly, glucose tolerance tests revealed greater

responsiveness in IGF-I receptor (+/-) males over control males and

significantly decreased responsiveness in females. Insulin levels

were not different between groups of mice. Body temperature,

physical activity, metabolic rate (measured by indirect calorimetry)

and food intake (short and long term) were also monitored and no

differences were detected.

Reduced GH–insulin–IGF-I signaling has also been associated with

reduced fertility in many experimental models. Dwarf mice (Ames,

Snell and Laron), flies (chico and INR mutants) and worms (DAF-2)

all exhibit delayed or reduced reproductive competence. By contrast,

the IGF-I receptor knockdown mice appeared to mature sexually

earlier with no adverse effects of the gene knockout (KO) detected

in litter size, frequency of pregnancy, mating behavior, estrous

cycle length or ovarian capacity. Aspects of male fertility outside

that of puberty were not addressed here.

For reasons mentioned previously, for this novel mouse longevity

mutant to conform to previous experimental longevity models, it was

of the utmost importance to test the animals' ability to resist

oxidative stress. These investigators challenged the IGF-I receptor-

knockdown and wild-type mice with paraquat, a systemic oxidative

stressor, and found that mutant mice resisted this challenge better,

resulting in significantly higher survival at 72 h, especially the

female IGF-I receptor-KO (+/-) mice. Cultured cells from IGF-I

receptor-+/- and -+/+ (normal) mice were also exposed to hydrogen

peroxide, and greater survival rates were detected in cells from

heterozygous KO mice.

Finally, intracellular signaling was also evaluated by cultured

embryonic fibroblasts derived from each genotype (-/-, +/-, +/+).

The heterozygous KO mice exhibited a 50% reduction in IGF-I receptor

levels and a decrease in IGF-I-induced phosphorylation of several

downstream targets of IGF-I receptor binding.

Discussion

This report provides significant support for the previous evidence

indicating that alterations in the signaling of GH–insulin–IGF-I

affect longevity. The IGF-I receptor-heterozygous mice were

comprehensively evaluated using a standard repertoire of biochemical

and physiological tests commonly applied in longevity studies.

Measures of cognition and oxidative damage are also of great

interest in these animals, because other longevity mutants have

shown a marked delayed decline in age-related cognitive activities,

a pertinent issue in human aging [12,13] . The extension of life

span in the IGF-I receptor-knockdown males was half that of the

females in this line, with a 19-month average life span of normal

mice, a value on the low end compared with other strains of mice.

However, they also reported confirmation of life span extension

using this IGF-I receptor mutation in hybrid mice.

In mammals, few experimental models of extended life span are

available. Although calorie restriction was the first method to

increase life span in mammals reproducibly (with a concomitant

reduction in serum IGF-I), the genetic models have now provided

isolation of a specific pathway that appears to be evolutionarily

well conserved. Stress resistance, reproduction and longevity appear

to be linked via this pathway, although the mechanisms are probably

independent [1,9] . Even studies using wild-derived mice suggest

that the reduced IGF-I is associated with longevity [14]. In

addition, the variability observed between experimental models

reflects differences in the magnitude of the reduction of GH–insulin–

IGF-I signaling. For example, Ames dwarf females are sterile and

outlive all of the other mouse mutants, suggesting that life

expectancy is related to the degree of gonadal suppression [15]. The

IGF-I receptor-knockdown mice display yet another level of reduced

signaling of this pathway exhibiting normal reproductive competence,

although the extension in life span is not as great as that seen in

the mouse mutants with low to non-detectable serum IGF-I levels and

more severe reproductive problems.

Conclusions

The key factor that is common to each of these longevity mutants

involves hormonal regulation of metabolic pathways, suggesting that

regulation of glucose metabolism, especially in mammals, is the

secret to slowing aging processes. The report by Holzenberger and co-

workers [1] is unique in that they have created a mouse with

specific IGF-I receptor deficiency. The adverse side effects

observed in experimental models with severely reduced IGF-I

signaling are not observed in these mice. This animal model fits

well within the growing body of literature suggesting that GH–

insulin–IGF-I signaling plays a major role in longevity

determination. Further examination of the pathways and mechanisms

utilized by IGF-I and related factors (GH and insulin) could suggest

potential therapeutic interventions to treat age-related disorders

and extend life span in humans.

References

[1] Holzenberger M. et al. (2003) IGF-I receptor regulates lifespan

and resistance to oxidative stress in mice.

Nature, 421:182-187. MEDLINE Cited by

[2] Brown-Borg H.M. et al. (1996) Dwarf mice and the aging process.

Nature, 384:33. MEDLINE Cited by

[3] Flurkey K. et al. (2001) Lifespan extension and delayed immune

and collagen aging in mutant mice with defects in growth hormone

production.

Proc. Natl. Acad. Sci. USA, 98:6736-6741. Full text MEDLINE Cited by

[4] Coschigano K.T. et al. (2000) Assessment of growth parameters

and life span of GHR/BP gene-disrupted mice.

Endocrinology, 141:2608-2613. MEDLINE Cited by

[5] Clancy D.J. et al. (2001) Extension of life-span by loss of

CHICO, a Drosophila insulin receptor substrate protein.

Science, 292:104-106. Full text MEDLINE Cited by

[6] Tatar M. et al. (2001) A mutant Drosophila insulin receptor

homolog that extends life-span and impairs neuroendocrine function.

Science, 292:107-110. Full text MEDLINE Cited by

[7] Kenyon C. et al. (1993) Caenorhabiditis elegans mutant that

lives twice as long as wild type.

Nature, 366:461-464. MEDLINE Cited by

[8] Fabrizio P. et al. (2001) Regulation of longevity and stress

resistance by Sch9 in yeast.

Science, 292:288-290. Full text MEDLINE Cited by

[9] Dillin A. et al. (2002) Timing requirements for insulin/IGF-I

signaling in C. elegans.

Science, 298:830-834. Full text Cited by

[10] Wolkow C.A. et al. (2000) Regulation of C. elegans life-span by

insulin like signaling in the nervous system.

Science, 290:147-150. Full text MEDLINE Cited by

[11] Brown-Borg H.M. et al. (2002) Effects of growth hormone and

insulin like growth factor-1 on hepatocyte antioxidative enzymes.

Exp. Biol. Med., 227:94-104. Cited by

[12] Bartke A. et al. (2002) Consequences of growth hormone (GH)

overexpression and GH resistance.

Neuropeptides, 36:201-208. ScienceDirect MEDLINE Cited by

[13] Kinney B.A. et al. (2001) Evidence that Ames dwarf mice age

differently from their normal siblings in behavioral and learning

and memory parameters.

Horm. Behav., 39:277-285. ScienceDirect MEDLINE Cited by

[14] R.A. et al. (2002) Longer life spans and delayed

maturation in wild-derived mice.

Exp. Biol. Med., 227:500-508. Cited by

[15] Bartke A. and Turyn D. (2001) Mechanisms of prolonged

longevity: mutants, knockouts, and caloric restriction.

J. Anti-Aging Med., 4:197-203.

[Guest guest]

The study mentioned below was performed on genetically modified

mice.

The increased longevity was created by the genetic modification,

and not by any other means. This study has been extensively

discussed in other forums, with the conclusion that the statement

quoted below must be modified by the words, " an effect observed

in genetic knockout mice " .

In true CR experiments on normal mice, it is *increased fat mass*

at isocaloric levels that correlates with increased lifespan.

You want to be as fat as possible on as few calories as possible

for maximum lifespan.

Since exercise (especially lots of exercise) causes you to lose fat,

and also causes you to increase your calorie intake, getting lots

of exercise is a poor CR investment.

This is a counter-intuitive surprise proven in the lab -- and a

frequent source of consternation to CR followers. It seems to be

a never-ending source of discussion, where people rub their eyes

in disbelief until they read the research results which all state

the same inevitable conclusion over and over again:

It is calories, calories, calories ...

-- Warren

=====================

> -----Original Message-----

> From: brian_sell2004 [mailto:brian_sell2004@...]

> Sent: Tuesday, June 15, 2004 9:36 PM

>

> Subject: [ ] Re: Popular Misconceptions about CR

> Lifestyle

>

> Have you seen this study Warren?

>

> Extended longevity in mice lacking the insulin receptor in

> adipose tissue

(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=A

bstract & list_uids=12543978)

>

> [ TinyURL: http://tinyurl.com/2f4vj ]

>

> The abstract concludes:

>

> Thus, a reduction of fat mass without caloric restriction can

> be associated with increased longevity in mice, possibly

> through effects on insulin signaling.

>

> Not only was average life span increased so was maximum life span.

>

> Regards,

>

>

>

>

>

>

>

>

>

> > >

> > > ... [because of my large amounts of exercise] I can eat late at

> > > night, eat large amounts and still do not gain, and am

> losing small

> > > amounts of weight...

> >

> > The best CR-way to be is this: to eat very little and to put on

> > weight very rapidly, even if you consume very few calories.

> >

> > Then to stay low in weight, you must eat very little, and you are

> > consuming the fewest calories possible, which is the origin of CR

> > benefits.

> >

> > Eating lots of food (and calories) and failing to put on

> weight is the

> > opposite of CR, but rather the public misconception and media

> > platitude of " healthful diet and exercise " .

> >

> > -- Warren

>

>

>

>

>

[Guest guest]

In a message dated 6/19/2004 7:42:12 AM Eastern Standard Time, warren.taylor@... writes:

Since exercise (especially lots of exercise) causes you to lose fat,

and also causes you to increase your calorie intake, getting lots

of exercise is a poor CR investment

As for the harm in excessive exercise with CR, I have read it suggested that the result may be too much wear and tear, not conducive to longevity. Peg

[Guest guest]

> The study mentioned below was performed on genetically modified

> mice.

>

> The increased longevity was created by the genetic modification,

> and not by any other means. This study has been extensively

> discussed in other forums, with the conclusion that the statement

> quoted below must be modified by the words, " an effect observed

> in genetic knockout mice " .

The mice were modified to prevent them from becoming fat in order to

study insulin signalling in fat tissue and to test the hypothesis

that reduced metabolic rate is responsible for the CR effects of

increased longevity. This study disconfirmed the metabolic rate

hypothesis.

> In true CR experiments on normal mice, it is *increased fat mass*

> at isocaloric levels that correlates with increased lifespan.

> You want to be as fat as possible on as few calories as possible

> for maximum lifespan.

>

> Since exercise (especially lots of exercise) causes you to lose

fat,

> and also causes you to increase your calorie intake, getting lots

> of exercise is a poor CR investment.

>

> This is a counter-intuitive surprise proven in the lab -- and a

> frequent source of consternation to CR followers. It seems to be

> a never-ending source of discussion, where people rub their eyes

> in disbelief until they read the research results which all state

> the same inevitable conclusion over and over again:

>

> It is calories, calories, calories ...

>

> -- Warren

>

Elderly Okiniwans have a low BMI, a low percentage of body fat, have

a high level of physical activity and are only mildly caloric

restricted in terms of kcal/kg of body weight.

In the calorie restricted retriever study linked to and cited by the

CR Society there was no increase in maximum lifespan even though it

as cited as evidence of increased longevity.

[Guest guest]

Hi folks:

I must say it is nice to have Warren around to straighten us each out

when we get off the main track and onto a 'siding'!!!

Following on from the " ...... increased fat mass ..... " observation

below, then the logical conclusion is (always remembering that logic,

not infrequently, can lead one astray) that we should certainly be

avoiding whey and skim milk products since they are alleged to

promote the burning of fat.

Of course, should anyone be aware of empirical evidence to the

contrary, I would very much like to be made aware of it.

Rodney.

> ..................................... In true CR experiments on

> normal mice, it is *increased fat mass*

> at isocaloric levels that correlates with increased lifespan.

> You want to be as fat as possible on as few calories as possible

> for maximum lifespan. .............................

> It is calories, calories, calories ...

>

> -- Warren

[Guest guest]

Hi :

It would be nice to know which of these characteristics of the

okinawans explains the fact that their *maximum* lifespan does not

appear to be extended. (Does anyone know of an okinawan older than

110 years? Let alone older than 120 or 130 ....... or 150.) Any

ideas?

Rodney.

> .............. Elderly Okiniwans have a low BMI, a low percentage

of body fat, have

> a high level of physical activity and are only mildly caloric

> restricted in terms of kcal/kg of body weight. ............

>

>

[Guest guest]

Hi All,

Remember, it is the abdominal fat that confers risk.

Fat tissue has a lower metabolic rate than muscle tissue.

WUSTL CRers had the heart disease risks of 10-year-olds.

Extra fat costs, at the same CR/weight level, are less muscle for

reducing falls, immune cells to prevent infections and bones that

should not fracture.

My % body fat is in the WUSTL study 82%, while the abdominal fat is

5.2%.

I have fallen. I have fractured.

Cheers, Al Pater.

> ..................................... In true CR experiments on

> normal mice, it is *increased fat mass*

> at isocaloric levels that correlates with increased lifespan.

> You want to be as fat as possible on as few calories as possible

> for maximum lifespan. .............................

[Guest guest]

> In true CR experiments on normal mice, it is *increased fat mass*

> at isocaloric levels that correlates with increased lifespan.

> You want to be as fat as possible on as few calories as possible

> for maximum lifespan.

Maybe I'm not reading this clearly, but do you know how absurd this

sounds to all the overweight people who cannot lose their relativley

high fat mass on a calorie restricted diet? There's plenty of

overweight people that do not consume excess calories and cannot

morph into a skinny body composition.

Your hypothesis would have us all eating high insulinic carbs, high

insulinic proteins and fats at each and every meal so as to get and

stay as fat as humanly possible on the least amount of calories. But

I haven't seen any science correlating insulin resistance, et al.

with increased maximum lifespan -- quite the opposite!

Logan

[Guest guest]

Hi Rodney,

The Okinawans and the only large mammal study done to date (dogs)

seems to be problematic for CR in explaining why maximum lifespan

has not been extended in either of these groups. Some have suggested

this may be due the difference in metabolic respiration (how energy

is made) between short-lived, high mortality mice, rats, flies, etc.

that reach reprodutive age as quickly as possible and larger animals

that are long-lived, with low mortality and reproduce later in life.

We'll have to wait for the results of the primate studies to get a

clearer picture.

Even if the benefit of extended maximum lifespan turns out to be a

pie in the sky, CR will still extend average lifespan considerably

delaying by years the onset of age-related disease and ending with a

rapid decline to the terminal point on the survival curve.

Cheers,

>

> > .............. Elderly Okiniwans have a low BMI, a low

percentage

> of body fat, have

> > a high level of physical activity and are only mildly caloric

> > restricted in terms of kcal/kg of body weight. ............

> >

> >