Re: What is CRON? - 18% more food?

[Guest guest]

That's causes it's total calories that count, not calories/body weight.

>From: " citpeks " <citpeks@...> Reply-To:

> Subject:

>[ ] What is CRON? - 18% more food? Date: Thu, 05 Aug 2004

>02:41:45 -0000

>

>I am still thinking about the paper by Mattson that we discussed recently

>(http://snipurl.com/4d7w). In particular, it seems to me that the CR mice

>eat more than the ad libitum (AL) mice on a weight basis.

>

>According to the paper, CR mice received 60% of the weight of the food

>eaten by AL mice. As a consequence, the growth of the CR mice was stunted

>and adult CR mice weighed 49% less than the AL mice. So, if the AL mice

>were getting F grams of food for a body weight of W, the CR mice were

>getting 0.6 F grams of food for a body weight of 0.51 W.

>

>Dividing 0.6 F by 0.51 W, we get 1.18 food/weight for the CR mice. To me

>this means that the CR mice were getting 18% more food on a weight basis

>than the AL mice.

>

>If CRON is about calories, calories, calories, it seems to me that CR mice

>are eating more than their share.

>

>Tony

>

[Guest guest]

Or, rather, that's 'cause it's total calories that count, not calories/body

weight. (Not quite awake, yet )

>From: " Dowling " <dowlic@...>

>Reply-

>

>Subject: RE: [ ] What is CRON? - 18% more food?

>Date: Thu, 05 Aug 2004 07:12:34 +0000

>

>That's causes it's total calories that count, not calories/body weight.

>

>

> >From: " citpeks " <citpeks@...> Reply-To:

> >

>Subject:

> >[ ] What is CRON? - 18% more food? Date: Thu, 05 Aug 2004

> >02:41:45 -0000

> >

> >I am still thinking about the paper by Mattson that we discussed recently

> >(http://snipurl.com/4d7w). In particular, it seems to me that the CR

>mice

> >eat more than the ad libitum (AL) mice on a weight basis.

> >

> >According to the paper, CR mice received 60% of the weight of the food

> >eaten by AL mice. As a consequence, the growth of the CR mice was

>stunted

> >and adult CR mice weighed 49% less than the AL mice. So, if the AL mice

> >were getting F grams of food for a body weight of W, the CR mice were

> >getting 0.6 F grams of food for a body weight of 0.51 W.

> >

> >Dividing 0.6 F by 0.51 W, we get 1.18 food/weight for the CR mice. To me

> >this means that the CR mice were getting 18% more food on a weight basis

> >than the AL mice.

> >

> >If CRON is about calories, calories, calories, it seems to me that CR

>mice

> >are eating more than their share.

> >

> >Tony

> >

>

>

[Guest guest]

Hi Tony:

What happened to Mattson's mice is not unusual. In fact it is

standard procedure.

In CR, an X percent decline in calories usually produces a percentage

decline in weight greater than X. So, yes, mice (people,

nematodes, .....) on CR are 'better' fed than those on ad lib,

especially if they are paying attention to ON.

Rodney.

> I am still thinking about the paper by Mattson that we discussed

> recently (http://snipurl.com/4d7w). In particular, it seems to me

> that the CR mice eat more than the ad libitum (AL) mice on a weight

> basis.

>

> According to the paper, CR mice received 60% of the weight of the

food

> eaten by AL mice. As a consequence, the growth of the CR mice was

> stunted and adult CR mice weighed 49% less than the AL mice. So, if

> the AL mice were getting F grams of food for a body weight of W, the

> CR mice were getting 0.6 F grams of food for a body weight of 0.51

W.

>

> Dividing 0.6 F by 0.51 W, we get 1.18 food/weight for the CR mice.

To

> me this means that the CR mice were getting 18% more food on a

weight

> basis than the AL mice.

>

> If CRON is about calories, calories, calories, it seems to me that

CR

> mice are eating more than their share.

>

> Tony

[Guest guest]

>>>>

From: " Dowling " <dowlic@h...>

Date: Thu Aug 5, 2004 3:15 am

Subject: RE: What is CRON? - 18% more food?

Or, rather, that's 'cause it's total calories that count, not

calories/body

weight. (Not quite awake, yet )

====

From: " Rodney " <perspect1111@y...>

Date: Thu Aug 5, 2004 7:23 am

Subject: Re: What is CRON? - 18% more food?

In CR, an X percent decline in calories usually produces a percentage

decline in weight greater than X. So, yes, mice (people,

nematodes, .....) on CR are 'better' fed than those on ad lib,

especially if they are paying attention to ON.

>>>>

: If it is only total calories that count, then only

five-foot short people who require few calories will live long, and

there is no hope for any 6-footers who have higher caloric

requirements!

Rodney: You are right. Your statement has been verified experimentally

many times. Trying to make sense of the situation, I came up with the

following:

===

Mice put on a 40% calorie restricted (CR) diet after 9 weeks of age

have an adult body weight that is 49% less than mice fed ad libitum

(AL) (http://snipurl.com/4d7w). Considering that CR mice receive 60%

of the food eaten by AL mice and that CR mice have an adult weight of

51% of the weight of AL mice, CR mice eat 18% more than AL mice on a

body weight basis.

How can this information be reconciled with the fact that the degree

of caloric restriction, within physiological limits, increases maximum

life span proportionally? Obviously, even if the CR mice are eating

relatively more food than AL mice, they are not eating as much as they

need, otherwise there would be no CR longevity effect. How can we

calculate the caloric deficit?

Let us start by noting that the adult weight for CR mice is

proportional to the degree of CR when CR is started at 9 weeks. This

can be expressed as:

CRW9 = ALW * (1 - CR) / (1 + CR/2)

Where CRW9 is the weight of the adult CR mice, ALW is the weight of

the AL mice, and CR is the caloric restriction (%CR /100). From this

we would estimate the weight of mice on 40% CR to be half of the AL

mice:

CRW9 = ALW*(1-0.4)/(1+0.4/2) = ALW*0.6/1.2 = ALW*0.5

The CR/2 term in the expression was chosen to fit the data from

Mattson. The formula needs to be checked to see if it agrees with

results obtained by using other degrees of caloric restriction.

However, for the case when CR is zero, CRW = ALW, which is what we

would expect.

At this point we need to introduce the term " Metabolic Capacity " (MC)

which would be the amount of food that can be eaten ad libitum by

animals of a specific size. AL mice, by definition, eat exactly 100%

of this amount. If we assume that MC decreases at a smaller rate than

the body size of the adult animals on CR diets decreases, there will

always be a caloric deficit for CR mice, in spite of the fact that CR

mice eat more on a body weight basis. Let us define MC as follows:

MC = (1 - CR) * (1 + CR/2)

For mice on a 40% CR diet, MC = 0.6*1.2 = 0.7

This can be interpreted as meaning that the adult 40% CR mice are

getting 60% of the food of AL mice, but that ad libitum they might

consume 70% of the food of AL mice. This would need to be verified by

an experiment where mice on a 40% CR diet, once having reached

maturity and their maximum 50% size, would be allowed to eat ad

libitum, and their consumption monitored. Do these mature, small mice

eat 70% of the food that AL mice eat? The results would allow

modifying the CR/2 term, as necessary. Note that if CR is zero, MC =

1, as it should be.

If these arguments have any validity, the real rate of restriction of

the 40% CR mice is 14% because of their smaller size (100 * (0.7 -

0.6)/0.7 = 14%), although the CR mice are eating 18% more than AL mice

on a body weight basis.

I am hoping that the readers of this forum who have the inclination

and the time to search the literature can provide data about:

1) the mature weight of CR mice vs. AL mice for various percentages of

CR to refine the calculation for CRW for mice started on CR at 9

weeks, or other stages of life.

2) provide any information about how much adult mice raised on CR

diets eat ad libitum to refine the notion of Metabolic Capacity.

CR experiments on mice show that a 40% restriction from adolescence

results in a stunted body size which requires fewer calories in

adulthood. From the assumptions about Metabolic Capacity, it seems

that CR started in adulthood should probably not exceed 14%.

Tony Zamora

[Guest guest]

Hi All,

But women eat less than men. At the same # of calories, a man's CR

would give greater longevity than a woman at the same calories.

Cheers, Al Pater.

> That's causes it's total calories that count, not calories/body

weight.

>

>

> >From: " citpeks " <citpeks@y...> Reply-To:

> >

Subject:

> >[ ] What is CRON? - 18% more food? Date: Thu, 05 Aug

2004

> >02:41:45 -0000

> >

> >I am still thinking about the paper by Mattson that we discussed

recently

> >(http://snipurl.com/4d7w). In particular, it seems to me that the

CR mice

> >eat more than the ad libitum (AL) mice on a weight basis.

> >

> >According to the paper, CR mice received 60% of the weight of the

food

> >eaten by AL mice. As a consequence, the growth of the CR mice was

stunted

> >and adult CR mice weighed 49% less than the AL mice. So, if the

AL mice

> >were getting F grams of food for a body weight of W, the CR mice

were

> >getting 0.6 F grams of food for a body weight of 0.51 W.

> >

> >Dividing 0.6 F by 0.51 W, we get 1.18 food/weight for the CR

mice. To me

> >this means that the CR mice were getting 18% more food on a weight

basis

> >than the AL mice.

> >

> >If CRON is about calories, calories, calories, it seems to me that

CR mice

> >are eating more than their share.

> >

> >Tony

> >

[Guest guest]

>>>

From: " Dowling " <dowlic@h...>

Date: Thu Aug 5, 2004 12:56 pm

Subject: Re: [ ] Re: What is CRON? - 18% more food?

How's dis?

" Life Sci. 2003 Mar 7;72(16):1781-802. Related Articles, Links

Is height related to longevity?

>>>

Now for the optimist's point of view: taller lives longer up to 5'5 "

(165 cm). I suppose it depends on whether you search for longevity or

mortality!

====

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

Retrieve & db=pubmed & dopt=Abstract & list_uids=12859029

Epidemiology. 2003 May;14(3):293-9.

Height and body mass index in relation to total mortality.

Engeland A, Bjorge T, Selmer RM, Tverdal A.

Division of Epidemiology, Norwegian Institute of Public Health,

Nydalen, Oslo, Norway. anders.engeland@...

BACKGROUND: The relation between body mass index (BMI) and mortality

is not clear in the literature. An inverse relation between height and

mortality has been suggested. We explore these relations in a very

large cohort in Norway. METHODS: We studied two million men and women,

age 20-74 years, who were measured during 1963-2000. These persons

were followed for an average of 22.1 years. We used proportional

hazard models in the analyses. Also, the optimal BMI (the BMI at the

time of measurement that was subsequently related to the lowest

mortality) was estimated. RESULTS: Over the study period, 723,000

deaths were registered. The relative risk of death by BMI showed a J-

or U-shaped curve, with the lowest rates of death at BMI between 22.5

and 25.0. In men, the optimal BMI increased from 21.6 when measured at

age 20-29 to 24.0 when measured at age 70-74. In women, the optimal

BMI was consistently higher, increasing from 22.2 to 25.7. Mortality

decreased with increased height in men; in women, mortality decreased

with height only up to heights of about 160-164 cm and then increased

among the tallest women. CONCLUSIONS: The relation between BMI and

mortality was J- or U-shaped, with the " optimal " BMI varying by age

and sex. Height was inversely related to mortality in men and in women

up to a height of 165 cm.

PMID: 12859029 [PubMed - indexed for MEDLINE]

[Guest guest]

Hi All,

See below.

> How's dis?

>

> " Life Sci. 2003 Mar 7;72(16):1781-802. Related Articles, Links

> > Is height related to longevity?

> > Samaras TT, Elrick H, Storms LH.

> >

> Over the last 100 years, studies have provided mixed results on the

> mortality and health of tall and short people. However, during the

last 30

> years, several researchers have found a negative correlation

between greater

> height and longevity based on relatively homogeneous deceased

population

> samples. Findings based on millions of deaths suggest that shorter,

smaller

> bodies have lower death rates and fewer diet-related chronic

diseases,

> especially past middle age. Shorter people also appear to have

longer

> average lifespans. The authors suggest that the differences in

longevity

> between the sexes is due to their height differences because men

average

> about 8.0% taller than women and have a 7.9% lower life expectancy

at birth.

> Animal experiments also show that smaller animals within the same

species

> generally live longer. The relation between height and health has

become

> more important in recent years because rapid developments in

genetic

> engineering will offer parents the opportunity to increase the

heights of

> their children in the near future. The authors contend that we

should not be

> swept along into a new world of increasingly taller generations

without

> careful consideration of the impact of a worldwide population of

taller and

> heavier people.

>

> PMID: 12586217 [PubMed - indexed for MEDLINE] "

Al Pater says:

For an earlier article on height versus longevity data, see the pdf-

available:

Gunnell D, J, Dieppe P.

Height and health: predicting longevity from bone length in

archaeological

remains.

J Epidemiol Community Health. 2001 Jul;55(7):505-7. No abstract

available.

PMID: 11413182 [PubMed - indexed for MEDLINE]

KEY POINTS

x Contemporary epidemiological studies

indicate that tall people tend to live

longer.

x The main causes of death are different

today from those in pre-industrial Britain.

x An examination of skeletal remains dating

from the 9th century suggests that stature

has been associated with reduced prema-ture

mortality for many centuries.

Contemporary studies show that taller people

live longer.1 2 Short stature is particularly associated

with an increased risk of cardiovascular

and respiratory mortality.2 It is uncertain whether

this association existed in earlier generations,

when disease patterns were quite dif-ferent.

Before the 19th century the main causes

of death were infection, malnutrition, accidents

and childbirth. Here we report an analysis of

the association between bone length, a marker

of stature, and age at death based on the skel-etal

remains of 490 subjects obtained from an

archaeological investigation in Barton on

Humber. Our aim was to determine whether

height-mortality associations existed in earlier

generations.

Methods

SOURCE OF SKELETAL REMAINS

The skeletal material was derived from an

excavation of approximately 3000 skeletons at

the site of St 's Church, Barton on Hum-ber

in the north east of England. The graves

date from the 9th century up to around 1850....

Sex and age at death were assigned to

skeletons ...

Aging adult remains is

more problematic and in this sample was

mainly based on an assessment of changes in

the pubic symphisis and the amount of wear to

dentition. Over the age of 45 it is not usually

possible to reliably divide into further age cat-egories.4 5

SAMPLE USED IN THIS ANALYSIS

Around a third of the 3000 skeletons belonged

to children and adolescents (aged <20).

Because bone growth is incomplete before

adulthood our analysis was restricted to those

aged 20 years or over at the time of death, as by

this age 96%–100% of adult height has been

attained. ... factors reduced the number of

skeletal remains available for this analysis to

490. ...

STATISTICAL ANALYSES

Analyses are based on the remains of adults to

whom it was possible to assign sex and age at

death. Associations between long bone length

(femur, tibia, fibula, humerus, ulna and

radius) and mortality were examined using

two logistic regression models, one using the

estimated age at death as < 30 years as the cut

point for premature mortality, the other using

<45 years. To control for the possible

confounding effects of secular increases in

height, a five level variable indicating the

period when the subject was buried was

included in all models—burial dates were cat-

egorised into 200 year bands. We included a

term for sex in all models. To enable us both to

compare the strength of associations with dif-ferent

bones and to allow us to produce a

pooled estimate of relative bone length for

each subject we converted all long bone

lengths to sex specific standard deviation (z)

scores. ... For each subject we also generated a

mean of the z scores for all the available arm

bones and for all available leg bones separately.

We also produced an index based on the mean

of the z scores for all available long bones. The

number of bones contributing to each index

varied from subject to subject.

The odds ratios presented are the increase

(or decrease) in odds of death at an early age

(<30 or <45) associated with a one standard

deviation increase in long bone length.

Results

There were 490 sets of remains with complete

data on sex, period of burial, approximate age

at death and measurement of at least one long

bone. Of these 321 (65%) were male and 169

(35%) female, the proportion of female

remains was higher in more recent burials.

One hundred and seventy eight (55%) of men

and 123 (73%) of women died before the age

of 45; 124 (39%) men and 94 (56%) of the

women died before 30. The median age at

death was 37 for men and 31 for women. A

total of 410 subjects had at least one available

arm bone and 370 had at least one available

leg bone. There was some evidence of a secu-lar

increase in long bone length. Over the years

studied radius length increased by 0.2 cm

(95% CI 0.1 to 0.3 p<0.01) every 200 years,

there were similar increases in the length of the

tibia (p=0.08), ulna (p<0.01) and humerus

(p=0.03). Women were more likely to die

young than were men. The odds ratio for

death before the age of 45 years was 1.94 (95%

CI 1.40 to 2.69) in women compared with

men.

The associations between long bone length

and age at death are given in table 1. For all

bones examined the odds ratios for death

before the age of 30 decreased as bone length

increased, with a one standard deviation

increase in bone length associated with a 10%–

20% decline the risk of premature mortality.

These associations reached conventional levels

of statistical significance for the combined

bone length index (p=0.03) and humerus

length (p=0.04) and were of borderline signifi-cance

in relation to the arm bone index

(p=0.08). For death before the age of 45 no

consistent pattern was seen, although for the

combined arm, leg and long bone indices

greater length was associated with a reduced

risk of premature mortality. There was no evi-dence

that either a particular long bone or

upper compared with lower limb bone length

was more strongly associated with premature

mortality. We found no evidence that associa-tions

between long bone length and premature

mortality differed in different burial periods.

Likewise, there were no significant interactions

between sex and bone length with respect to

their effects on mortality and the strength of

the associations was similar in men and

women.

To check that our findings were not biased

by the inclusion of subjects whose growth was

incomplete we repeated the analyses without

subjects with an estimated age at death of <25

years. The odds ratios were essentially un-changed.

Discussion

This analysis provides evidence from an

archaeological sample that long bone length is

associated with age at death—those with

smaller bones tend to die younger. There are a

number of limitations to this analysis. Firstly,

we do not know how representative those with

complete remains and buried within this

graveyard were of the general population,

although we have no reason to believe that the

selection processes involved in obtaining our

sample will bias the results we have obtained.

Secondly, we have no information on the

socioeconomic status of the subjects examined

here and affluence is generally associated with

longevity and greater stature. Thirdly, we do

not know the causes of death and so cannot

determine whether the stature-mortality asso-ciations

differ for particular diseases as they do

in contemporary populations.2

Fourthly, we have examined 18 different bone length-

mortality associations, increasing the likeli-hood

of false positive findings (type I error).

However, as many of the bone lengths are

intercorrelated we might expect some consist-ency

across the hypothesis tests we have

conducted. Lastly, our assessment of age at

death is inevitably crude and may be subject to

some error, again this error is likely to be non-differential

with respect to long bone length

and is most likely to attenuate the associations

we have observed.

Height is an indicator of childhood health

and nutrition,6 so height-mortality associations

have been interpreted as suggesting either that

exposures in childhood have long term influ-ences

on adult health or that those factors

leading to poor childhood growth continue to

operate and affect health in adulthood. Mecha-nisms

for height-mortality associations in the

past may differ from those today,2 for example

short stature may have increased the risk of

death in childbirth and this may account for

the higher risk of premature mortality in

women. However, short bones, it would

appear, have always been a marker of a short

life.

Funding: none.

Conflicts of interest: none

1 Waaler HT. Height, weight and mortality: the Norwegian

experience. Acta Med Scand 1984;679 (suppl):1–56.

2 Davey G, Hart C, Upton M, et al. Height and risk of

death among men and women: aetiological implications of

associations with cardiorespiratory disease and cancer

mortality. J Epidemiol Community Health 2000;54:97–103.

3 Mays S, M. Sex determination in skeletal remains. In:

M, May S, eds. Human osteology in archaeology and foren-sic

science. London: Greenwich Medical Media, 2000:117–30.

4 Buikstra JE, Ubelaker DH, eds. Standards for data collection

from skeletal remains. Fayettville, AR: Arkansas Archaeologi-cal

Survey Research Series, 1994:no 44.

5 M. Ageing adults from the skeleton. In: M, May S,

eds. Human osteology in archaeology and forensic science.

London: Greenwich Medical Media, 2000:61–80.

6 Floud R, Wachter K, A. Height, health and history.

Nutritional status in the United Kingdom, 1750–1980.

Cambridge: Cambridge University Press, 1990.

[Guest guest]

Hi folks:

My impression has always been that to a considerable extent height is

a function of childhood nutrition. Pretty much everyone in South

America is about six or more inches shorter than us in North

America. They are poor and don't get a lot to eat, especially not as

much meat as us.

So, if people are short because they had less nutrition as children,

then we could easily suppose that they might live longer because they

were eating a more CRON-like diet as children, and likely as adults

too. The problem in South America as regards lifespan is the near

absence of health services. If you get appendicitis today you

probably will not be around two weeks from now. (So I am not saying

the average lifespan is high in South America, despite their 'CR'

diet).

Rodney.

> Up to 5'5 " ? Sounds rather shortish to me!

>

>

> >From: " citpeks " <citpeks@y...>

> >Reply-

> >

> >Subject: [ ] Re: What is CRON? - 18% more food?

> >Date: Thu, 05 Aug 2004 17:28:38 -0000

> >

> > >>>

> >From: " Dowling " <dowlic@h...>

> >Date: Thu Aug 5, 2004 12:56 pm

> >Subject: Re: [ ] Re: What is CRON? - 18% more food?

> >How's dis?

> > " Life Sci. 2003 Mar 7;72(16):1781-802. Related Articles, Links

> >Is height related to longevity?

> > >>>

> >

> >Now for the optimist's point of view: taller lives longer up to

5'5 "

> >(165 cm). I suppose it depends on whether you search for

longevity or

> >mortality!

> >

> >====

> >

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

> >Retrieve & db=pubmed & dopt=Abstract & list_uids=12859029

> >Epidemiology. 2003 May;14(3):293-9.

> >Height and body mass index in relation to total mortality.

> >Engeland A, Bjorge T, Selmer RM, Tverdal A.

> >Division of Epidemiology, Norwegian Institute of Public Health,

> >Nydalen, Oslo, Norway. anders.engeland@f...

> >

> >BACKGROUND: The relation between body mass index (BMI) and

mortality

> >is not clear in the literature. An inverse relation between height

and

> >mortality has been suggested. We explore these relations in a very

> >large cohort in Norway. METHODS: We studied two million men and

women,

> >age 20-74 years, who were measured during 1963-2000. These persons

> >were followed for an average of 22.1 years. We used

proportional

> >hazard models in the analyses. Also, the optimal BMI (the BMI at

the

> >time of measurement that was subsequently related to the lowest

> >mortality) was estimated. RESULTS: Over the study period, 723,000

> >deaths were registered. The relative risk of death by BMI showed a

J-

> >or U-shaped curve, with the lowest rates of death at BMI between

22.5

> >and 25.0. In men, the optimal BMI increased from 21.6 when

measured at

> >age 20-29 to 24.0 when measured at age 70-74. In women, the optimal

> >BMI was consistently higher, increasing from 22.2 to 25.7.

Mortality

> >decreased with increased height in men; in women, mortality

decreased

> >with height only up to heights of about 160-164 cm and then

increased

> >among the tallest women. CONCLUSIONS: The relation between BMI and

> >mortality was J- or U-shaped, with the " optimal " BMI varying by age

> >and sex. Height was inversely related to mortality in men and in

women

> >up to a height of 165 cm.

> >

> > PMID: 12859029 [PubMed - indexed for MEDLINE]

> >

[Guest guest]

Unfortunately, this discussion got sidetracked trying to determine

whether short or tall people live longer. That is not the point that

I was trying to make. I am trying to figure out how CR mice can eat

18% more food than AL mice on a weight basis and still be calorically

restricted.

I suggest that the answer is that as the CR mice become stunted by the

restrictive diet their smaller bodies have a smaller requirement for

food, but their metabolic capacity decreases at a smaller rate than

their body size, thereby creating caloric restriction. I hope that by

understanding what happens in mice we can make better decisions for

our own diets.

For example, the Institute of Medicine suggests the *minimum* number

of calories for a male as: Height 5'0 " , 1879 Cal, Height 5'6 " , 2114

Cal, Height 6'0 " , 2348 Cal. These numbers apparently come from the

base metabolic rates required to just breathe and lie down with no

activity. I think that our practice of caloric restriction should be

based on numbers like these that correspond to our physical structure

and not some arbitrary number of calories like 1500 pulled out of the

air.

By understanding the animal models and how much *real* caloric

restriction they are under, considering their size, I also feel that

we will get a better handle on what is practical or applicable for

humans. The experiment that I suggested to measure what an adult

50%-size CR mouse eats at libitum could let us know the nutritional

requirements for the mice based on their size. This may turn out to

be equivalent to what the Institute of Medicine suggests for humans.

In any case, the information will allow us to be more quantitative in

our approach to CR and our understanding of the elusive " set point " ,

etc.

Tony

=======Message 14018

From: " citpeks " <citpeks@y...>

Date: Thu Aug 5, 2004 12:15 pm

Subject: Re: What is CRON? - 18% more food?

Mice put on a 40% calorie restricted (CR) diet after 9 weeks of age

have an adult body weight that is 49% less than mice fed ad libitum

(AL) (http://snipurl.com/4d7w). Considering that CR mice receive 60%

of the food eaten by AL mice and that CR mice have an adult weight of

51% of the weight of AL mice, CR mice eat 18% more than AL mice on a

body weight basis.

How can this information be reconciled with the fact that the degree

of caloric restriction, within physiological limits, increases maximum

life span proportionally? Obviously, even if the CR mice are eating

relatively more food than AL mice, they are not eating as much as they

need, otherwise there would be no CR longevity effect. How can we

calculate the caloric deficit?

Let us start by noting that the adult weight for CR mice is

proportional to the degree of CR when CR is started at 9 weeks. This

can be expressed as:

CRW9 = ALW * (1 - CR) / (1 + CR/2)

Where CRW9 is the weight of the adult CR mice, ALW is the weight of

the AL mice, and CR is the caloric restriction (%CR /100). From this

we would estimate the weight of mice on 40% CR to be half of the AL

mice:

CRW9 = ALW*(1-0.4)/(1+0.4/2) = ALW*0.6/1.2 = ALW*0.5

The CR/2 term in the expression was chosen to fit the data from

Mattson. The formula needs to be checked to see if it agrees with

results obtained by using other degrees of caloric restriction.

However, for the case when CR is zero, CRW = ALW, which is what we

would expect.

At this point we need to introduce the term " Metabolic Capacity " (MC)

which would be the amount of food that can be eaten ad libitum by

animals of a specific size. AL mice, by definition, eat exactly 100%

of this amount. If we assume that MC decreases at a smaller rate than

the body size of the adult animals on CR diets decreases, there will

always be a caloric deficit for CR mice, in spite of the fact that CR

mice eat more on a body weight basis. Let us define MC as follows:

MC = (1 - CR) * (1 + CR/2)

For mice on a 40% CR diet, MC = 0.6*1.2 = 0.7

This can be interpreted as meaning that the adult 40% CR mice are

getting 60% of the food of AL mice, but that ad libitum they might

consume 70% of the food of AL mice. This would need to be verified by

an experiment where mice on a 40% CR diet, once having reached

maturity and their maximum 50% size, would be allowed to eat ad

libitum, and their consumption monitored. Do these mature, small mice

eat 70% of the food that AL mice eat? The results would allow

modifying the CR/2 term, as necessary. Note that if CR is zero, MC =

1, as it should be.

If these arguments have any validity, the real rate of restriction of

the 40% CR mice is 14% because of their smaller size (100 * (0.7 -

0.6)/0.7 = 14%), although the CR mice are eating 18% more than AL mice

on a body weight basis.

I am hoping that the readers of this forum who have the inclination

and the time to search the literature can provide data about:

1) the mature weight of CR mice vs. AL mice for various percentages of

CR to refine the calculation for CRW for mice started on CR at 9

weeks, or other stages of life.

2) provide any information about how much adult mice raised on CR

diets eat ad libitum to refine the notion of Metabolic Capacity.

CR experiments on mice show that a 40% restriction from adolescence

results in a stunted body size which requires fewer calories in

adulthood. From the assumptions about Metabolic Capacity, it seems

that CR started in adulthood should probably not exceed 14%.

Tony Zamora

[Guest guest]

> > That's causes it's total calories that count, not calories/body

> weight.

> >

> >

> > >From: " citpeks " <citpeks@y...> Reply-To:

> > > To:

> Subject:

> > >[ ] What is CRON? - 18% more food? Date: Thu, 05

Aug

> 2004

> > >02:41:45 -0000

> > >

> > >I am still thinking about the paper by Mattson that we discussed

> recently

> > >(http://snipurl.com/4d7w). In particular, it seems to me that

the

> CR mice

> > >eat more than the ad libitum (AL) mice on a weight basis.

> > >

> > >According to the paper, CR mice received 60% of the weight of

the

> food

> > >eaten by AL mice. As a consequence, the growth of the CR mice

was

> stunted

> > >and adult CR mice weighed 49% less than the AL mice. So, if the

> AL mice

> > >were getting F grams of food for a body weight of W, the CR mice

> were

> > >getting 0.6 F grams of food for a body weight of 0.51 W.

> > >

> > >Dividing 0.6 F by 0.51 W, we get 1.18 food/weight for the CR

> mice. To me

> > >this means that the CR mice were getting 18% more food on a

weight

> basis

> > >than the AL mice.

> > >

> > >If CRON is about calories, calories, calories, it seems to me

that

> CR mice

> > >are eating more than their share.

> > >

> > >Tony

> > >

[Guest guest]

Hi Tony:

I did not mean to be part of the sidetracking of the question you

raised. (Apologies). But I am having difficulty getting my brain

around this issue. So do not have much to contribute to it.

However, one point I will make is that I do not think the proposition

that '40% restriction means 50% weight loss' applies only when

restriction is started very early in life.

My IMPRESSION is that the percentage weight loss also exceeds percent

restriction even when restriction is started after maturity. If this

is correct, then 'stunting' is not the explanation. If I am wrong

about this please feel free to straighten me out.

Rodney.

> Unfortunately, this discussion got sidetracked trying to determine

> whether short or tall people live longer. That is not the point

that

> I was trying to make. I am trying to figure out how CR mice can eat

> 18% more food than AL mice on a weight basis and still be

calorically

> restricted.

>

> I suggest that the answer is that as the CR mice become stunted by

the

> restrictive diet their smaller bodies have a smaller requirement for

> food, but their metabolic capacity decreases at a smaller rate than

> their body size, thereby creating caloric restriction. I hope that

by

> understanding what happens in mice we can make better decisions for

> our own diets.

[Guest guest]

>>>>>

From: " Dowling " <dowlic@h...>

Date: Thu Aug 5, 2004 5:50 pm

Subject: Re: What is CRON? - 18% more food?

>From: " citpeks " <citpeks@y...>

>Date: Thu, 05 Aug 2004 20:25:28 -0000

>I think that our practice of caloric restriction should be

>based on numbers like these that correspond to our physical structure

>and not some arbitrary number of calories like 1500 pulled out of the

>air.

Not " out of the air " at all! The less calories, the more life

extension, in a linear fashion, till one gets down below 50%-60% of

" ad lib. "

>>>>

,

I think that the term " ad lib. " is as meaningless as " set point " . How

many calories can you eat in a day? It depends on your appetite,

physical activity, and choice of foods. An average size male can

easily consume 3500 Calories per day. On that basis, 2000 calories

per day would be a 42% CR diet. The problem is that we don't know how

much we can eat.

You say CR provides " more life ... till one gets below 50%... " . OK,

If the average male can eat 3500 calories per day, 1500 Calories is

57% CR. This is already *dangerous* territory if you are interested

in life extension. Basing a diet on what you can eat ad lib., or what

you think that you would eat ad lib. IS pulling numbers out of the

air.

I advocate basing human CR diets on individual basal metabolism once

the BMI is in a normal range. (It does not make sense to base it on

the basal metabolism for underweight or overweight persons.) Basal

metabolism can be computed based on height, weight, respiration

studies, etc. depending on the accuracy that you desire. AND it is an

objective measure that does not depend on how hungry you are, or how

much you think that you can eat, or other subjective factors.

At the same time we have to understand the effect of CR diets started

after maturity.

>>>>

From: " Rodney " <perspect1111@y...>

Date: Thu Aug 5, 2004 9:17 pm

....

My IMPRESSION is that the percentage weight loss also exceeds percent

restriction even when restriction is started after maturity. If this

is correct, then 'stunting' is not the explanation. If I am wrong

about this please feel free to straighten me out.

>>>>

From the pictures that I have seen of holocaust victims, I cannot say

that their bones shrank during their starvation. So, there is no

significant 'stunting' in height. However, when you consume fewer

calories than your basal metabolism requires, there is going to be

some emaciation as the muscles and other tissues are reduced to the

level that can be supported by the available nutrition. The loss of

weight may indeed be more than the percent restriction.

If you are a 5'8 " male whose minimum calorie requirement is 2,200

calories per day based on basal metabolism and sedentary life style.

By eating only 2000 calories per day ( 10% CR) you will lose weight

until your body adjusts to the new diet. Any additional restrictions

to the diet should be based on your ORIGINAL basal metabolism based on

your height, rather than your new smaller weight.

I feel that a lot of the advice given on this and other boards about

*how much* to eat does not have any scientific basis as long as " ad

libitum " and " set point " are being used as the criteria for the diets.

Basing the diets on OBJECTIVE physical measurements, like basal

metabolism, height, or BMI would be more acceptable.

This is why I am scrutinizing the mice experiments by using

mathematical equations. I hope that there are generalizations that

have applications to human diets.

Tony Zamora

[Guest guest]

Hi Tony:

These are interesting issues you raise. Certainly it would be much

better if we had an objecive way to determine what constitutes 40%

restriction for each of us (or 20% restriction, or whatever). A

major problem, I think, is that everyone is different.

A few thoughts: In my case, perhaps I am unusual, there is nothing

vague about the term 'Set point'. I believe my set point is my

weight at age 22 when I was doing ~20 hours a week of fairly intense

training for endurance sports. That happened to be 173 pounds. It

is the weight I believed all my life until a couple of years ago to

be my ideal weight. That number was confirmed, incidentally, by

formulae relating 'ideal' weight to height and wrist circumference.

In the past whenever I have found I am five or ten pounds over that

weight, I have taken steps to return it to 173 pounds.

On the other hand, for me the term 'Ad lib' is definitely vague. I

could easily eat 3500 calories a day, and more if I put my mind to

it - and I would put on (quite literally) hundreds of pounds of

weight per year if I did so. So let me suggest to you an alternative

measure which I think makes more sense as a substitute for 'ad lib'.

I will call it 'con ad stab'. That is short for 'conventional ad

stable'.

Walford and everyone else who uses the term 'ad lib' is looking for a

benchmark measure of food consumed for a person who is neither over

weight according to the conventional wisdom, nor excessively slim.

So perhaps the benchmark number of calories from which to calculate

degrees of restriction should be that number which MAINTAINS WEIGHT

at what the conventional wisdom considers to be ideal weight.

More specifically, I would define 'con ad stab' as the number of

calories needed to maintain weight in the general vicinity of BMI =

25; WC/H = 0.500; BF% = 21%. (These are my perception of what the

conventional wisdom thinks are about right for people who are neither

over weight nor excessively slim). Perhaps not coincidentally, those

numbers (the BMI = 25; WC/H = 0.500; and BF% = 21%) coincide very

closely in my case with what I believe to be my set point - 173

pounds.

It would be interesting to know whether or not that is also true for

others. If this happy coincidence does not only apply to me, then

perhaps we 'have something'. If everyone's numbers are all over the

lot, then obviously we don't.

Whatever that number of calories turns out to be (perhaps it was 2000

per day for me a year ago, required to maintain my weight at those

three parameters) degrees of restriction can be calculated from

there. In my case 40% restriction would be 1200 calories. (More

extreme than I am prepared to try in the absence of much more

information).

Does this help?

Rodney.

> >>>>>

> From: " Dowling " <dowlic@h...>

> Date: Thu Aug 5, 2004 5:50 pm

> Subject: Re: What is CRON? - 18% more food?

> >From: " citpeks " <citpeks@y...>

> >Date: Thu, 05 Aug 2004 20:25:28 -0000

> >I think that our practice of caloric restriction should be

> >based on numbers like these that correspond to our physical

structure

> >and not some arbitrary number of calories like 1500 pulled out of

the

> >air.

> Not " out of the air " at all! The less calories, the more life

> extension, in a linear fashion, till one gets down below 50%-60% of

> " ad lib. "

> >>>>

>

> ,

>

> I think that the term " ad lib. " is as meaningless as " set point " .

How

> many calories can you eat in a day? It depends on your appetite,

> physical activity, and choice of foods. An average size male can

> easily consume 3500 Calories per day. On that basis, 2000 calories

> per day would be a 42% CR diet. The problem is that we don't know

how

> much we can eat.

>

> You say CR provides " more life ... till one gets below 50%... " . OK,

> If the average male can eat 3500 calories per day, 1500 Calories is

> 57% CR. This is already *dangerous* territory if you are interested

> in life extension. Basing a diet on what you can eat ad lib., or

what

> you think that you would eat ad lib. IS pulling numbers out of the

> air.

>

> I advocate basing human CR diets on individual basal metabolism once

> the BMI is in a normal range. (It does not make sense to base it on

> the basal metabolism for underweight or overweight persons.) Basal

> metabolism can be computed based on height, weight, respiration

> studies, etc. depending on the accuracy that you desire. AND it is

an

> objective measure that does not depend on how hungry you are, or how

> much you think that you can eat, or other subjective factors.

>

> At the same time we have to understand the effect of CR diets

started

> after maturity.

>

> >>>>

> From: " Rodney " <perspect1111@y...>

> Date: Thu Aug 5, 2004 9:17 pm

> ...

> My IMPRESSION is that the percentage weight loss also exceeds

percent

> restriction even when restriction is started after maturity. If this

> is correct, then 'stunting' is not the explanation. If I am wrong

> about this please feel free to straighten me out.

> >>>>

>

> From the pictures that I have seen of holocaust victims, I cannot

say

> that their bones shrank during their starvation. So, there is no

> significant 'stunting' in height. However, when you consume fewer

> calories than your basal metabolism requires, there is going to be

> some emaciation as the muscles and other tissues are reduced to the

> level that can be supported by the available nutrition. The loss of

> weight may indeed be more than the percent restriction.

>

> If you are a 5'8 " male whose minimum calorie requirement is 2,200

> calories per day based on basal metabolism and sedentary life

style.

> By eating only 2000 calories per day ( 10% CR) you will lose weight

> until your body adjusts to the new diet. Any additional

restrictions

> to the diet should be based on your ORIGINAL basal metabolism based

on

> your height, rather than your new smaller weight.

>

> I feel that a lot of the advice given on this and other boards about

> *how much* to eat does not have any scientific basis as long as " ad

> libitum " and " set point " are being used as the criteria for the

diets.

> Basing the diets on OBJECTIVE physical measurements, like basal

> metabolism, height, or BMI would be more acceptable.

>

> This is why I am scrutinizing the mice experiments by using

> mathematical equations. I hope that there are generalizations that

> have applications to human diets.

>

> Tony Zamora

[Guest guest]

Hi All,

1. I believe that the 25 BMI classification as normal is a high

estimate.

I lost weight from 152 pounds at age 20 to less than 100 pounds, and

I eat over 1800 calories/day.

Cheers, Al Pater.

--- In , " Rodney " <perspect1111@y...>

wrote:

> Hi Tony:

>

> These are interesting issues you raise. Certainly it would be much

> better if we had an objecive way to determine what constitutes 40%

> restriction for each of us (or 20% restriction, or whatever). A

> major problem, I think, is that everyone is different.

>

> A few thoughts: In my case, perhaps I am unusual, there is nothing

> vague about the term 'Set point'. I believe my set point is my

> weight at age 22 when I was doing ~20 hours a week of fairly

intense

> training for endurance sports. That happened to be 173 pounds. It

> is the weight I believed all my life until a couple of years ago to

> be my ideal weight. That number was confirmed, incidentally, by

> formulae relating 'ideal' weight to height and wrist

circumference.

> In the past whenever I have found I am five or ten pounds over that

> weight, I have taken steps to return it to 173 pounds.

>

> On the other hand, for me the term 'Ad lib' is definitely vague. I

> could easily eat 3500 calories a day, and more if I put my mind to

> it - and I would put on (quite literally) hundreds of pounds of

> weight per year if I did so. So let me suggest to you an

alternative

> measure which I think makes more sense as a substitute for 'ad

lib'.

> I will call it 'con ad stab'. That is short for 'conventional ad

> stable'.

>

> Walford and everyone else who uses the term 'ad lib' is looking for

a

> benchmark measure of food consumed for a person who is neither over

> weight according to the conventional wisdom, nor excessively slim.

> So perhaps the benchmark number of calories from which to calculate

> degrees of restriction should be that number which MAINTAINS WEIGHT

> at what the conventional wisdom considers to be ideal weight.

>

> More specifically, I would define 'con ad stab' as the number of

> calories needed to maintain weight in the general vicinity of BMI =

> 25; WC/H = 0.500; BF% = 21%. (These are my perception of what the

> conventional wisdom thinks are about right for people who are

neither

> over weight nor excessively slim). Perhaps not coincidentally,

those

> numbers (the BMI = 25; WC/H = 0.500; and BF% = 21%) coincide very

> closely in my case with what I believe to be my set point - 173

> pounds.

>

> It would be interesting to know whether or not that is also true

for

> others. If this happy coincidence does not only apply to me, then

> perhaps we 'have something'. If everyone's numbers are all over

the

> lot, then obviously we don't.

>

> Whatever that number of calories turns out to be (perhaps it was

2000

> per day for me a year ago, required to maintain my weight at those

> three parameters) degrees of restriction can be calculated from

> there. In my case 40% restriction would be 1200 calories. (More

> extreme than I am prepared to try in the absence of much more

> information).

>

> Does this help?

[Guest guest]

Hi All,

I prefer long term prospective studies such as:

Int J Obes Relat Metab Disord 1998 Jun;22(6):544?8.

Body mass and 26 y risk of mortality among men who never smoked: a re?

analysis among men from the Adventist Mortality Study.

Lindsted KD, Singh PN. ... Prospective ... effects due to age at

measurement of BMI, smoking history and race ... age 30?54 y and ...

age 55?74 y ...men; ... 5062 men ... 1960?1985 ... years 15?26 ...

effects due to antecedent illness were not apparent and a significant

positive, linear relation between BMI and all?cause mortality was

consistently found among middle?aged (30?54 y) and older (55?74 y)

men. ... analyses of ... years 15?26 revealed that the positive

linear trends with all?cause mortality, were primarily due to excess

risk of cardiovascular disease and cancer ... Among older men, a

significant inverse relation between BMI and respiratory disease

mortality risk ... during ... years 15?26 ... attenuated ... with no

baseline history of respiratory disease. ...

PMID: 10588076 [PubMed - indexed for MEDLINE]

--- In , " Jeff Novick " <jnovick@p...>

wrote:

> >>25 BMI may not be " normal, " but in the US, it's pretty near the

mean!

>

> It seems like somewhere between 18-22 may be the healthiest.....

>

> First....

>

> " Impact of Overweight on the Risk of Developing Common Chronic

Diseases

> During a 10-Year Period Arch Intern Med. 2001;161:1581-1586

> Alison E. Field, ScD; et al

>

> Conclusions: During 10 years of follow-up, the incidence of

diabetes, gallstones, hypertension, heart disease, colon cancer, and

stroke (men

> only) increased with degree of overweight in both men and women.

Adults who were overweight but not obese (ie, 25.0BMI29.9) were at

> significantly increased risk of developing numerous health

conditions. Moreover, the dose-response relationship between BMI and

the risk of

> developing chronic diseases was evident even among adults in the

upper half of the healthy weight range (ie, BMI of 22.0-24.9),

suggesting

> that adults should try to maintain a BMI between 18.5 and 21.9 to

minimize their risk of disease.

>

> Second.....

>

> Relation between body mass index and mortality in an unusually slim

cohort

>

> M Thorogood, P N Appleby, T J Key, J Mann

> J Epidemiol Community Health 2003;57:130-133

>

> Conclusions: Lean men and women (BMI <18 kg/m2) experience

increased all cause mortality compared

> with those with a BMI between 20 and 22 kg/m2. This pattern is not

seen for cancer mortality,

> but is found for cardiovascular and respiratory diseases.

>

> I emailed one of the authors, Appleby, when this came out and

this is what he sent in response to my question..

>

> " " The death rate ratios were adjusted for age at recruitment, sex,

smoking, and pre-existing cardiovascular disease or diabetes.

> Further, the same pronounced upturn in mortality among the very

slim (BMI<18 kg/m2) was found among men, women, vegetarians,

> non-vegetarians, never smokers, and subjects aged less than 60 at

recruitment, and after excluding the first 5 years of follow-up.

>

> Deaths from accidents & violence were included in the " all other

causes of death " category. Mortality from this *cause* was also

> significantly higher in the slimmest category (BMI<18) compared

with the reference category (BMI 20-22). " "

[Guest guest]

Hi All,

Studies have corrected for early deaths due to underlying diseases by

eliminating the first 17 years, and found a linear relationship.

This, is long-term.

heers, Al Pater.

> > >>25 BMI may not be " normal, " but in the US, it's pretty near

the

> mean!

> >

> > It seems like somewhere between 18-22 may be the healthiest.....

> >

> > First....

> >