CR works in primates

[Guest guest]

Hi All,

CR works in primates appears to be the reply to the title to the introduction of

what promises to be an issue of Biogerontology that is of note: " Will dietary

restriction work in primates? "

Will dietary restriction work in primates?

Biogerontology (Online) DOI: 10.1007/s10522-006-9007-0 Issue: Online First 06

May,

2006, 3 pages

Weindruch

Abstract This issue of Biogerontology addresses whether dietary

restriction

(DR) “... can increase longevity in all species, particularly in human beings.”

The

possibility that DR can increase longevity in all species seems a trivial issue

compared to that of DR’s potential efficacy in people. The striking phylogenetic

breadth of DR’s longevity increasing effect supports the notion of human

translatability. The available evidence in primates (human and nonhuman)

suggests

that it is highly probable that DR will increase the span of good health (and

the

average lifespan) but the magnitude of this predicted increase is unknown.

Robust

survival data for monkeys subjected to highly controlled DR will be available in

~25

years; similar data for large numbers of human practitioners of DR appear to be

many

decades away.

Introduction ... The issue posed by the editors of this volume, that is

whether

dietary restriction (DR) ‘‘... can increase longevity in all species,

particularly

in human beings’’ is addressed. Three lines of evidence germane to this issue

are

discussed. These are:

• the phylogenetic breadth of DR’s lifespan-increasing effect

• evidence from our nonhuman primate DR study

• evidence from epidemiological studies and from investigations of human

practitioners of DR

Taken together, the data support a high likelihood that DR will be shown to

increase

human longevity.

Phylogenetic breadth of DR’s effect on longevity. ... DR can extend

lifespan in

diverse animals (e.g., the protozoans, rotifers, worms, water fleas, spiders,

laboratory rodents, etc.) (Weindruch and Walford 1988). It also increases the

average lifespan of dogs (Kealy et al. 2002). Accordingly, it would be

surprising if

DR would fail to increase longevity in primates, although others have argued on

evolutionary grounds that it would be only minimally effective. A

weather-related

position championed by de Grey (Gerontology 2005) leads to the assumption-filled

conclusion that DR may increase human lifespan by only 2–3 years. Phelan and

Rose

(2005) developed a ‘‘hypothesis-neutral model describing the relationship

between

diet and longevity’’ and conclude that the benefits of DR in humans ‘‘would be

quantitatively small.’’

A recent study (Nagasaka et al. 2005) is germane to the question of whether

DR

will exert lifespan-extending effects in all species. These investigators

observed

no effect of DR on longevity in an annual fish (anu). However, it remains

possible

that another DR regimen may display efficacy in increasing lifespan in this

model.

Evidence from a nonhuman primate DR study ... We are investigating a cohort

of

78 rhesus monkeys on either DR or a control diet (Ramsey et al. 2000). Cohorts

were

established in 1989 (males: 15 control, 15 DR) and 1994 (females: 15 control, 15

DR;

males: 8 Control, 8 DR). The animals were 8–14 years old at onset. The monkeys

on DR

display several signs of improved health and an emerging survival advantage

compared

to age-matched controls (manuscript in preparation). At our Primate Center,

rhesus

monkeys display an average lifespan of ~27 years and a maximum lifespan ~40

years.

Thus it may require another ~25 years to obtain full survival data on this

cohort

(or even longer if DR proves to be highly effective in primate aging

retardation).

Evidence from human DR studies ... Studies germane to DR in humans were

recently (and thoughtfully) reviewed by Dirks and Leeuwenburgh (2006). They

point

out that, despite the promise of DR to slow aging, there are several potential

negative ‘‘side effects’’ (e.g., hypotension, loss of libido, cold sensitivity,

etc.) that deserve attention.

Indirect support for efficacy of DR in humans is provided by

epidemiological

studies, which attempt to estimate the habitual caloric intakes of large numbers

of

people and link these data to disease susceptibility of the individual. My

conversations with nutritional epidemiologists indicate that it is difficult to

obtain highly accurate data on caloric intakes in large numbers of people. That

said, there is evidence linking lower caloric intakes to a decreased risk of

developing many of the main age-related diseases (see Weindruch and Sohal 1997).

In

Okinawa, where energy intake of adults was 17% lower than the average in Japan,

death rates from cerebrovascular disease, cancer, and heart disease were 31–41%

lower than the national average (Kagawa 1978). A study in Sweden showed that a

high

body–mass index and high levels of total food consumption and energy intake were

risk factors for prostate cancer (Groenberg et al. 1996; Andersson et al. 1996).

Epidemiologic data suggest that caloric intake is directly correlated with the

incidence of colorectal, breast, and stomach cancers (Albanes 1990).

Clearly, the most direct evidence for efficacy of DR in humans comes from

studies of cardiovascular aging in long-term practitioners of DR. Fontana et al.

(2004) reported that such individuals show markedly improved risk factor

profiles

for protection against developing cardiovascular disease. They also display many

of

the core features of DR such as reductions in circulating insulin, glucose and C

reactive protein levels. These adaptations suggest that systemic adjustments in

energy metabolism and inflammatory status are shared with those observed in

rodents.

Recently, these investigators observed that these individuals display fewer

signs of

cardiovascular aging (diastolic function) compared to normal weight controls

(Meyer

et al. 2006).

Conclusions .... Based on the collective evidence it would be surprising if

appropriately applied, chronic DR would not significantly increase the average

lifespan of people. Effects on maximum lifespan in monkeys should be clear in

~25

years while robust data in people appears to be further in the future.

-- Al Pater, alpater@...

__________________________________________________

[Guest guest]

It occurs to me, at the rate lifespan is increasing now in U.S., the average citizen may not need CR or anything more in 25 years. This in spite of not a lot of headway preventing cancer, but a breakthrough in treatment, eg, or artificial kidneys, could leap us to 100 yo in 10 yrs.

I truly believe an artificial heart could slow aging, as well.

Regards.

[ ] CR works in primates

Hi All,CR works in primates appears to be the reply to the title to the introduction ofwhat promises to be an issue of Biogerontology that is of note: "Will dietaryrestriction work in primates?" Conclusions .... Based on the collective evidence it would be surprising ifappropriately applied, chronic DR would not significantly increase the averagelifespan of people. Effects on maximum lifespan in monkeys should be clear in ~25years while robust data in people appears to be further in the future.-- Al Pater, alpater@...

[Guest guest]

It occurs to me, at the rate lifespan is increasing now in U.S., the average citizen may not need CR or anything more in 25 years. This in spite of not a lot of headway preventing cancer, but a breakthrough in treatment, eg, or artificial kidneys, could leap us to 100 yo in 10 yrs.

I truly believe an artificial heart could slow aging, as well.

Regards.

[ ] CR works in primates

Hi All,CR works in primates appears to be the reply to the title to the introduction ofwhat promises to be an issue of Biogerontology that is of note: "Will dietaryrestriction work in primates?" Conclusions .... Based on the collective evidence it would be surprising ifappropriately applied, chronic DR would not significantly increase the averagelifespan of people. Effects on maximum lifespan in monkeys should be clear in ~25years while robust data in people appears to be further in the future.-- Al Pater, alpater@...