Okinawan CRers

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Hi All,

What can we learn from the Okinawans? The pdf of the below paper is available.

Willcox DC, Willcox BJ, Todoriki H, Curb JD, Suzuki M.

Caloric restriction and human longevity: what can we learn from the Okinawans?

Biogerontology. 2006 Jun 30; [Epub ahead of print]

PMID: 16810568 http://tinyurl.com/zposa

... older Okinawans, who appear to have undergone a mild form of prolonged

CR

for about half their adult lives. ... Caloric (or dietary) restriction (CR) ...

The

question of whether or not CR would work in humans may be one of the most

significant unanswered questions in biogerontology. ... CR not only will work

but in

fact available epidemiological evidence indicates that CR may already have

contributed to an extension of average and maximum life span in one human

population

and appears to have lowered risk for age associated chronic diseases in other

human

populations. We review the human studies in the context of a special human

population that we believe has undergone prolonged CR while also maintaining a

high

quality diet—a necessary condition for CR to manifest its beneficial effects.

....

concentrate on long term human studies (Heilbronn and Ravussin 2003; Masoro

2005;

Dirks and Leeuwenburgh 2006). ... (Fontana et al. 2004). ... (Meyer et al.

2006). A

key question is whether or not these systemic changes are reflective of a more

youthful physiology and will enhance health and lifespan if continued over a

longer

time period. ... Baltimore Longitudinal Study of Aging (BLSA) ... noted that

healthy

men who displayed three " biomarkers of the CR phenotype " —lower insulin levels,

lower

body temperature and a slower decline in levels of the hormone

dehydroepiandrosterone sulfate (DHEA-S) also had significantly longer survival

(Roth

et al. 2002). ... Honolulu Heart Program cohort where blood glucose in middle

age

strongly predicts late life survival ( et al. 1999).

... Only one long-term epidemiological prospective study (>30 years) has

directly addressed the issue of caloric intake and human longevity. This 36-year

follow-up study reported a weak trend for lower allcause mortality in healthy

non-smoking Japanese-American men suggesting that those who consumed a modestly

low

energy intake (85% of group mean) had the lowest risk for all-cause mortality [

The

pdf-available http://tinyurl.com/ggvhp paper] . There was higher mortality risk

when caloric intake dropped below 50% of the group mean. This is consistent with

previous animal findings that show decreased risk for mortality from age

associated

diseases and increased life span under a CR regimen of up to 50% restriction.

....

Low caloric intake was first reported in the Okinawan population by Hokama et

al.

(1967) who showed that Okinawan school children consumed only 62% of the

calories of

other Japanese school children. Kagawa (1978) confirmed low caloric intake (83%

of

Japan average) in the Okinawa adult population from the 1972 Japan National

Nutrition Survey and documented anthropometric and morbidity data from older

Okinawans that were consistent with CR. Kagawa (1978) hypothesized that this may

have been partly responsible for the long and healthy lives of Okinawans. Death

rates from heart disease, cancer and cerebral vascular disease were found to be

only

60 to 70% of that of the Japan average and the all-cause mortality rate for

60–64

year olds was only half that of other Japanese. A later study published by Chan

et

al. (1997) also reported dietary and phenotypic data in Okinawan septuagenarians

and

centenarians consistent with CR.

Our recent analysis of long-term trends in whole population caloric intake

and

energy balance for the years beginning in 1949 demonstrates that the Okinawan

septuagenarian population appeared to be in a relative " energy deficit "

consistent

with CR until the late 1960s, eating approximately 11% fewer calories

(approximately

1,785 kcal per day) than would normally be recommended for maintenance of body

weight according to the -Benedict equation (Willcox et al. Unpublished

data).

The body mass index (BMI) of adult Okinawans also remained stable at a very lean

21

kg/m2 and peak body weight was reached in young adulthood and appeared

relatively

stable until elderly ages (Willcox et al. Unpublished data). These dietary and

anthropometric data are consistent with adaptation to a long-term energy deficit

and

fit proposed epidemiologic definitions by a recent US National Institutes of

Health

panel (see Lee et al. 2001) of the human CR phenotype (i.e. no weight gain after

early adulthood).

Moreover, nutritional studies suggest that the traditional Okinawan diet,

with

its high intake of green leafy and yellow root vegetables, sweet potatoes as a

dietary staple, and soy as a principle protein supplemented by small amounts of

fish

and meat, was adequate in most nutrients and particularly high in antioxidant

vitamins [not pdf-available http://tinyurl.com/ffa3u etc].

Was there a CR effect? ... If a CR phenomenon occurred for the current

generation of elderly Okinawans then there should be biomarker evidence of

CR-linked

delayed physiological aging. Thus, it is of keen interest that recent findings

from

our ongoing study of Okinawa’s elderly population show that Okinawan

septuagenarians, who would have undergone CR until at least middle age according

to

the previous population data, exhibit higher DHEA levels when compared to

age-matched Americans not subjected to CR (Willcox et al. Unpublished data). In

addition, if delayed aging occurred in Okinawans, then there should be a

rightward

shift in the survival curve, with increases in both average lifespan and maximum

lifespan. Indeed, survival curves for Okinawan, Japanese and U.S. populations

calculated based on life table data for the year 1995 do show increases in both

average and maximum lifespan in the Okinawan population compared to Japanese and

American populations, consistent with CR. Average lifespan (measured as 50th

percentile survival) and maximum lifespan (measured as 99th percentile survival)

in

the Okinawan, Japanese and U.S. populations were 83.8 and 104.9 years, 82.3 and

101.1 years, and 78.9 and 101.3 years, respectively (Willcox et al. Unpublished

data).

Finally, age-adjusted mortality for specific age-related diseases

(especially

cardiovascular diseases) is extremely low in elderly Okinawans compared to other

age-matched Japanese or Americans [not pdf-available http://tinyurl.com/ffa3u

etc] .

Thus, life expectancy at older ages is extremely long in Okinawa. For the

septuagenarian cohort, life expectancy from age 65 is the longest in Japan, and

possibly the world, at 24.1 years for females and 18.5 years for males (Japan

Ministry of Health, Labor and Welfare, 2005). This compares to 22.5 years and

17.6

years for the same birth cohort in mainland Japan (Japan Ministry of Health,

Labor

and Welfare 2000) and 19.3 years and 16.2 years for corresponding U.S. birth

cohorts

of females and males respectively (U.S. Centers for Disease Control and

Prevention

2003). Also consistent with a longer life expectancy at older ages is the high

numbers of centenarians at approximately 50 per 100,000 or about 4–5 times the

average for most industrialized countries (Japan Ministry of Health, Labor and

Welfare 2005).

Other factors may also be contributing to the exceptional longevity of the

Okinawans such as genetic factors, specific nutritional components of the diet

(high

anti-oxidants), social support and/or health care [not pdf-available

http://tinyurl.com/ffa3u , pdf-available http://tinyurl.com/ebjwt etc] .

However,

the forces of morbidity and mortality act most strongly at older ages and it is

at

these ages one would expect to see the most marked phenotypic differences and

the

most marked survival advantage, had CR occurred in the Okinawans, and indeed

this is

the case.

Should we restrict our calories? ... Some scientists who study the

mechanisms

of aging suggest that it is unlikely that the maximum lifespan of humans can be

extended by any intervention, including caloric restriction (Hayflick 2004). It

has

also been argued that while CR is likely to be almost universal in its

beneficial

effects on longevity, the benefit to humans is likely to be small, even if

humans

restrict their caloric intake substantially and over long periods of time

(Phelan

and Rose 2005). The latter argument derives from observations of complex

differences

between species (such as amount of energy allocated to reproduction) and the

fact

that underlying physiological mechanisms that determine longevity are not

necessarily the same between species. Furthermore, there are potential health

concerns, particularly if practiced incorrectly (too severe) or at vulnerable

(too

young, too old, pregnancy) life stages ([not pdf-available

http://tinyurl.com/fvy5l

etc]

While fully acknowledging that the nature of the life-extending action of

CR

may differ among species, we believe these views to be overly pessimistic and

not

reflective of the available evidence. However, we believe that people should not

attempt to restrict calories to the extreme levels seen in animal studies (up to

60%) because human studies, although promising, have not fully addressed issues

such

as quality of life and other potential side effects. With that caveat in mind,

cautious approaches to lowering calories (mild CR) among adults while

maintaining

optimal nutrient intakes would still likely result in significant health

benefits.

In fact, recent findings show that even 8% CR has beneficial effects on specific

biochemical and inflammatory biomarkers [not pdf-available

http://tinyurl.com/fvy5l

]

We cite the following reasons for a more optimistic view of the potential

benefits of the CR lifestyle for human beings: ... accumulated evidence of 70

years

of CR studies ... (from yeast to mammals). As such, it would be unusual if it

did

not work in some positive capacity in humans as well. Second, studies in

progress

with non-human primates (who share over 95% of our genes and have similar

reproductive physiology) on a CR regimen, while not yet conclusive, are showing

early results consistent with previous animal data. Third, short-term and

longer-term studies of humans under a true CR paradigm have shown dramatic

changes

in physiology and metabolic shifts similar to other animals. Fourth, our

research

shows that older Okinawans (ages-65 plus) exhibit a CR-like phenotype and ate a

low

calorie diet over a prolonged period of time. Calories in the Okinawan

population

were approximately 11% fewer than what would usually be recommended for their

body

weight and activity levels (based on the -Benedict equation) but only for

half

their adult lives.

Yet, even with this mild CR-like regimen older Okinawans have gained an

additional 6% survival time from age 65 (1.3 years) versus other Japanese and an

additional 20% survival time (3.6 years) versus Americans. Given the large

number of

factors that influence human lifespan, this is also surprisingly similar to the

gain

in lifespan observed in prior animal studies (i.e. 10–20% calorie reduction

leads to

a 10–20% increase in lifespan). Most importantly, the Okinawans appear to have

gained an increased health span, with almost a decade of disability-free life

expectancy beyond what typical Western populations experience.

Lastly, while Okinawans were not consciously practicing CR, they did

develop

cultural habits that led to the kind of prudent food choices that maximize

nutritional properties of foods while minimizing caloric density as would be the

favored strategy for anyone who attempts a CR regimen. Simply avoiding

calorie-dense

refined sugars, saturated fats and processed foods and replacing them with

nutrient-dense but calorie poor vegetables, fruits and legumes will not only

likely

lead to spontaneous weight loss through lower caloric intake but would also

result

in a vastly increased intake of health-enhancing phytonutrients, including key

vitamins and minerals, antioxidants and flavonoids. Practicing a little

restraint at

the dinner table may also have its benefits. " Eat until you are 80% full " (or

hara

hachi-bu) is the advice that Okinawan grandmothers have given for years and the

science of CR appears to be proving that the wisdom of the elders still rings as

true as ever.

-- Al Pater, alpater@...

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