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[A1CR]

All:

> CRONie_IG wrote or quoted:
> > CRONie_AJS wrote,

>>> I mean the life
>>> extension to reasonably expect when comparing
>>> severe skeleton-like CR to just maintaining BMI
>>> 20-21 and eating and exercising sensibly. This
>>> latter state I don't even consider to be "real" CR.

>> There seems to be a view that a BMI in such a range
>> is not "real CR." And that's what needs to change.

Without condemning anyone for their choice of Caloric intake, exercise
level, or actual BMI (which latter isn't a metric of CR in the first
place (ob/ob mice, Schwarzenegger, Asian anthropometry (see (1)), yadda yadda), and restricting the discussion to the scientific and without
intending to raise hackles founded mostly in CR "identity politics" or
internal self-identification conflicts, it bears saying that by good
scientific experimental methodology, a BMI (or, better: burden of
visceral/omental fat) that is "merely" in the "normal," "healthy" range
would NOT be CR in a better-quality scientific experiment in mice, and
the benefitts observed in those animals can't be SIMPLY extrapolated to
the human case.

Everyone knows that excess adiposity (and, more precisely, excess
visceral/omental fat) is life-shorteningly bad for one, but eliminating
this by reducing body fat (by exercise or by CR) is a mixture of (a)
simply removing a cause of PREMATURE death, and (b) a true CR
*anti/aging* effect -- but even this latter is a bit conceptually
slippery, as one is thereby arguably simply avoiding ACCLERATED aging,
not slowing it down relative to some norm. (Ie, there IS some underlying
soundness to Hayflick's objection to the CR effect (he just happens to
be empirically wrong about its generalizability)).

If a study is to be a genuine test of CR as an intervention in aging,
scientists must carefully separate out the life-SHORTENING eeffects of
obesity from CR's anti-aging effect per se. This has in fact been done
in the better-designed CR experiments -- notably, the absolutely
critical midliffe-onset studies by Weindruch and/or Walford (2,4), the
similarly breakthrough late-life study by Stephen Spindler et al (3),
and WEindruch's important (partially-published) LEF-funded study
comparing CR to dietary supplements (5), as opposed to short-term
studies on effects on acute challenges like toxins or trauma (eg,
Mattson's group's work)) -- by restricting the *control* animals by
10-20% below their literal "ad libitum" intake, so that what is reported
in the abstract as eg "40% CR" is precisely 40% CR as DISTINGUISHED
FROM, by comparison, a "restricted" diet in the sense of a murine
"healthy BMI"/obesity-avoidance diet.

Thus, for all but a few genuine metabolic freakazoids (and no offense to
metabolic freakazoids -- I love you all!), who despite the "fat
acceptance" movement's propaganda are incredibly rare (most folks who
think their overweight is metabolic simply don't accurately assess
and/or measure their actual Caloric intake and/or expenditure), a level
of reduced energy intake and/or increased exercise leading to a BMI of
20 or 21 (again, a better metric would be visceral or omental fat)
simply *isn't* properly reported as "CR" if in using taht term we are
thinking about the remarkable anti- *aging* effects observed in such
studies. Such folk, with no disparagement intended (achieving a BMI of
20 starting from overweight or obesity is a major accomplishment!!), are
best thought of as the CONTROL GROUP, not the CR cohort, in such
experiments.

>> I
>> used to weight 220 lbs, I was obese. After CR I went
>> way down to 140. However, any CR-induced weight below
>> 220 would be doing CR and could have benefits.

It certainly WILL have benefits: indeed, the benefits to you are MORE
CERTAIN than they are in a person like me (who was already quite slim
before starting CR), because premature death from obesity is a pretty
darned well-established fact inhumans, whereas substantial scientific
uncertainty remains about whether CR per se will be of any benefit
whatever in our species -- or will be of any greater benefit than the
paltry gains to be expected from the resulting low disease risk profile
(ie, VERY low cholesterol and blood glucose (as opposed to merely
not-toxically-high levels)). Remember, ELIMINATING heart disease,
cancer, diabetes, and stroke as causes of death from the human
population would increase the average person's life expectancy by <=
15.3 years (7) -- and when calculating 'the average,' of course, one
includes the morbidly obese, smokers, etc.

The gain in healthy life expectancy to be expected from a CR effect
restricted to the resulting REALLY GOOD cardio risk factors clearly will
be significantly less than what one would expect from ELIMINATING these
diseases, and the benefit thereof, as vs having merely 'normal' ones, is
not likely substantial; thus, if CR doesn't ADDITIONALLY extrapolate to
humans as an intervention against AGING, it's really rather a waste of
time, as vs a simple "healthy weight," RELATIVELY healthy (food-pyramid)
diet, etc: there just isn't much room to gain (cf. (6)). Plus, there are
RISKS associated with a very low CR-induced BMI, as we hear ad nauseum
but as bears remembering: frature risk, lack of internal energy reserves
for severe illness, etc.

CRONie_TT wrote:
> However the term "calorie restriction" is casually applied where
> it is not clear what control population the restriction is relative to.
>
> I do think that - there is a substantial case for casual
> use of the term "CR" /mainly/ indicating the low end of
> the calorie intake spectrum - with everything else being
> classified as "obesity avoidance".
>
> I definitely think that there needs to be some convenient
> way of distinguishing between those things terminologically;

I think you just have .

> there is a continuum between them - but the gene expression
> profile of severely restricted organisms has undergone a
> kind of switch - and there needs to be a way to reference
> that concept.

Indeed. But NB that the fact that any such line will be drawn in the
sand rather than in the Book of Life isn't an objection to draawing it,
any more than it is when we do the same thing with the arbitrary cutoffs
that we use to distinguish eg. glycemic normalcy from prediabetes or
diabetes using fasting and/or postprandial glucose and/or HbA1C, or
normal blood pressure from prehypertension and hypertension, etc. To
think otherwise illustrates the real (as opposed to popular) meaning of
the "slippery slope" fallacy.

> Whatever way is chosen, there is bound to be some
> perception that those doing what we currently call
> "obesity avoidance" are being a bit half-hearted -
> while those restricting further are the restriction
> propellor heads.

That is def'ly an unfortunate effect from the POV of the sociology of
our group, and of exploiting (and yes, I am here invoking that word's
pejorative connotation) the CR data to motivate overweight and obese
folks to achieve a 'healthy weight;' but the distinction is crucial from
the POV of intellectual honesty about what one is doing and what one can
expect from it.

Indeed, ignoring the fact that OA is properly regarded as the CONTROL
state, and not as "moderate CR," creates a quite false sense of what one
is accomplishing with one's chosen lifestyle -- not just for the OA
practitioiner, but also for the practitioner of CR per se. The former
will anticipate that hir eg 15% restriction from an
overweight-supporting "ad libitum" Caloric intake will, ceteris paribus,
lead to a 15% increase in life expectancy from the av'g LS of the
population as a whole, when in fact it will simply NORMALIZE hir life
expectancy to that f a person whose expectancy has not been REDUCED by
overweight.

More subtly, the latter will overestimate hir *degree* of CR,
calculating from hir AL even if s/he began overweight. Thus, eg, s/he
will think of a 30% reduction from hir overweight-supporting "ad
libitum" Caloric intake as equivalent to 30% CR in the rodent studies in
terms of potential to affect life expectancy, when (taking eg 15% CR as
an obesity-avoidance level of "restriction") it would be more accurately
thought of as (1-[(1-0.3)/(1-0.15)] = ) 18%. (Such an error is on top of
the slipperiness of the whole concept of trying to calculate "%CR" based
on a cohort of 1).

This will (among other problems) encourage a false sense of security,
discouraging the OA practitioner from considering CR per se, and the CR
practiioiner from considering more severe CR; it also tends to create
excessive confidence in the ability of CR itself, in humans, to affect
aging, esp at middle age and beyond. This will have the secondary
negative effect of reducing the existential urgency of developing
genuine anti-aging biomedicine (plug: support the MPrize for the
successful development of radical anti-aging biomedicine in mice
<http://tinyurl.com/zuzw8> and/or give directly to research advancing
individual planks in my boss, Aubrey de Grey's, Strategies for
Negligible Senescence platform (in dollars <http://tinyurl.com/j6msv>
and as graveyard soil for the xenohydrolase project
<http://tinyurl.com/pqlq8> !!).

And additionally:


> However, I certainly don't think the society should
> distance itself in any way from those whose interest
> is "obestiy avoidance".

No, but OA is already a very well-served studied paradigm in humans, and
is already promoted and supported by public health authorities and a
variety of *respectable* private enterprises. And there is the opposite
danger: that the distinct needs of people engaged in a genuine
EXPERIMENT, with substantial risks, by quite dramatically reducing
Caloric intake and/or BMI, will be lost in the equally "valid" concerns
and needs of the "healthy" BMI and diet group. What is needed out there
is exactly to promote, serve, and support the fringe element.

One fear is of course that by emphasizing the latter, we will alienate
folks who are overweight or make the average Jo(e) feel that if s/he
can't/won't go for really radical CR, s/he may as well just go back to
the Krispy Kreme. I don't deny that this happens; I do deny that it's a
good reason to fail to make these distinctions. Walford, similarly,
hammered at the nutritioin "authorities" for the lame-assed,
half-hearted efforts at improved nutrition epitomized by the Food
Pyramid (esp as originally designed), which they made on just such grounds:

------------
nutritional and medical authorities ... are obsessed with the notion
that they must keep it simple, that they cannot stray too far & too
rapidly in their reccomendations from waht people habitually eat,
otherwise patients will be confused and noncompliant. But recent ...
figures show that [such strategies around fat intake] ... has backfired.
People limit fat intake but feel thereby free to eat low-fat foods in
unlimited quantities, resulting in an average increase in daily calorie
consumption ...

In my view, it is better to lay out what is optimally helhty and
lifespan-promoting, rather than arrogantly deciding what people can bear
to hear. A good example is the ... "food pyramid." At the bottom ... are
["starches"] rather than vegetables and fruits, which should be there
... And behold, on the top of the pyramid are the sweets ... In short,
it appears "reccomended" that you consume small quantities of these
unhealthy materials. I myself occasionally eat ... sweets; but I
certainly would not give them an official 'reccomendation.' They do not
belong on top of a food pyramid. They belong on top of a tombstone [the
Grand Old Man could write! -MR] [BT120YD, pp 93-4].
--------------

Again, similarly, we aren't going to learn anything particularly
surprising or informative about health -- and nothing about aging or the
human extrapolability of the CR effect seen in rodents -- from CALERIE
(see the recent yawner in JAMA (8)); we ARE learnign soething, slowly,
from the WUSTL study in the cohort of CR Society members (9-11), despite
its clear methodological weakness, precisely because the participants
(and esp the males) are all ABNORMALLY skinny.

CRONie_BMD wrote:
> 2006-05-03 21:14 CRONie_IG wrote:
>
>> The concept of a near-starvation diet should be
>> replaced with that of simply eating less than
>> otherwise, and the icon of the emaciated freak should
>> be replaced with that of the svelte Greek.
>
>
> This "concept replacement" has been my goal for years.

Such a switch in imaging would put a more attractive face on CR for most
people, and may therefore have the advantage of helping some folks on
the fence to take up CR when they mightn't otherwise (or, more likely,
to take up OA); but ultimately it isn't, IMO, an accurate way to
characterize things, and in the long term I sincerely fear that it will
be counterproductive to the goal of promulgating and supporting the
practice of CR as a *life extension* intervention in humans, and CRS as
an *effective* and *serious* LE organization.

I end this post with a link to a previous, infamous one from a couple of
years back, beloved of mine Consort, the Delight of the Gods:

http://lists.calorierestriction.org/cgi-bin/wa?A2=ind0209&L=crsociety&P=R14554


1. Mandavilli A, Cyranoski D. Asia's big problem. Nat Med. 2004
Apr;10(4):325-7. No abstract available. PMID: 15057217 [PubMed - indexed
for MEDLINE]
[Summarized previously here:

http://lists.calorierestriction.org/cgi-bin/wa?A2=ind0506&L=crsociety&P=R37898

Summary: people across Asia (including South Asia) have similar rates of
type 2 diabetes as the general US population, yet they have much lower
rates of "obesity" assessed by US BMI cutoffs. The latter datum is
however an *illusion* of slimness, when in fact these populations
actually have similar amounts of actual fat, packed into different
anthropometry. "In Caucasians, a BMI of 30 correlates with approximately
25% body fat in men and 30% in women. But for the same age, sex, and
BMI, ... Asians have a higher fat percentage ... People with a BMI as
low as *20* can nevertheless be *obese* when judged by body fat [my
emphasis]." In Polynesia, obesity-induced NIDDM is even MORE prevalent
than in the USA.
--------------------

2. Weindruch R, Walford RL. Dietary restriction in mice beginning at 1
year of age: effect on life-span and spontaneous cancer incidence.
Science. 1982 Mar 12;215(4538):1415-8. PMID: 7063854 [PubMed - indexed
for MEDLINE]

3. Dhahbi JM, Kim HJ, Mote PL, Beaver RJ, Spindler SR. Temporal linkage
between the phenotypic and genomic responses to caloric restriction.
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5524-9. Epub 2004 Mar 25.
PMID: 15044709 [PubMed - indexed for MEDLINE]

4. Pugh TD, Oberley TD, Weindruch R.
Dietary intervention at middle age: caloric restriction but not
dehydroepiandrosterone sulfate increases lifespan and lifetime cancer
incidence
in mice.
Cancer Res. 1999 Apr 1;59(7):1642-8.
PMID: 10197641 [PubMed - indexed for MEDLINE]

5. Lee CK, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R, Prolla
TA.
The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction
on life
span and gene expression patterns in mice.
Free Radic Biol Med. 2004 Apr 15;36(8):1043-57.
PMID: 15059645 [PubMed - indexed for MEDLINE]

6. Primary prevention of coronary heart disease in women through diet
and lifestyle. N Engl J Med. 2000 Jul 6;343(1):16-22.
PMID: 10882764

7. Science 1990 Nov 2;250(4981):634-40
In search of Methuselah: estimating the upper limits to human longevity.
Olshansky SJ, Carnes BA, Cassel C
PMID: 2237414

8. Heilbronn LK, de Jonge L, Frisard MI, DeLany JP, Larson-Meyer DE,
Rood J, Nguyen T, Martin CK, Volaufova J, Most MM, Greenway FL, Smith
SR, Deutsch WA, Williamson DA, Ravussin E; Pennington CALERIE Team.
Effect of 6-month calorie restriction on biomarkers of longevity,
metabolic adaptation, and oxidative stress in overweight individuals: a
randomized controlled trial.
JAMA. 2006 Apr 5;295(13):1539-48.
PMID: 16595757 [PubMed - indexed for MEDLINE]

9.Meyer TE, Kovacs SJ, Ehsani AA, Klein S, Holloszy JO, Fontana L.
Long-term caloric restriction ameliorates the decline in diastolic
function in humans.
J Am Coll Cardiol. 2006 Jan 17;47(2):398-402.
PMID: 16412867 [PubMed - indexed for MEDLINE]

10: Fontana L, Meyer TE, Klein S, Holloszy JO.
Long-term calorie restriction is highly effective in reducing the risk
for atherosclerosis in humans.
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63. Epub 2004 Apr 19.
PMID: 15096581 [PubMed - indexed for MEDLINE]

11: Fontana L, Shew JL, Holloszy JO, Villareal DT.
Low bone mass in subjects on a long-term raw vegetarian diet.
Arch Intern Med. 2005 Mar 28;165(6):684-9.
PMID: 15795346 [PubMed - indexed for MEDLINE]