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Mouse CRers more physically fit?

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Hi All,

It seems that, contrary to what most human CRers often report, CRed mice perform

better in terms of physical exercise that ad lib mice.

See the below.

Ishihara H, Wenying F, Kouda K, Nakamura H, Kohno H, Nishio N, Sonoda Y.

Effects of dietary restriction on physical performance in mice.

J Physiol Anthropol Appl Human Sci. 2005 May;24(3):209-13.

PMID: 15930808

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

ct & list_uids=15930808

Introduction

Historically, Homo sapiens experienced periods of food

shortage and famine, and adapted to restrictions in their food

supply (Baker, 1988). In contrast, most people living in the

modern technological society can obtain more than enough

food. As a result, the prevalence of obesity and related diseases

is increasing in the world; indeed, overnutrition has been

recognized as a form of malnutrition (World Health

Organization, 1997).

Dietary restriction (DR) without malnutrition affects

physiological functions (Frame et al., 1998; Kouda et al., 2004)

and prolongs lifespan (Yu, 1996; Weindruch and Sohal, 1997)

in laboratory animals. Preliminary data indicate that these

findings are applicable to humans. A study of humans

produced observations like those of the animal studies,

although life prolongation has not yet been shown (Walford

et al., 2002). In laboratory animals, DR has also been reported

to prevent cerebrovascular and cardiovascular diseases (Kemi

et al., 2000), malignancy (Yoshida et al., 1997; Birt et al.,

1999), autoimmune diseases (Kubo et al., 1992; Urao et al.,

1995), and allergic diseases (Dong et al., 2000; Kouda et al.,

2000; Fan et al., 2001; Nakamura et al., 2004).

Whereas there are numerous reports about disease

prevention by dietary restriction, there are few reports about

the effects of dietary restriction on physical performance.

Concerning dietary restriction and physical activity, it has been

shown that DR animals have higher activity levels, as

demonstrated through their exercise in voluntary running

wheels (Goodrick et al., 1983; Holloszy et al., 1991; Giles

et al., 1992; Mc et al., 1997). Recently, Horská et al.

(1999) reported that the combination of caloric restriction and

free exercise acts synergistically to decrease muscle fatigue

and to improve muscle bioenergetics. However, little is yet

known about the effects of dietary restriction on physical

performance.

In the present study, we measured several reactions during

assigned tasks and attempted to estimate physical performance

in the kinds of activity involved in averting risks to life.

.....All mice were given a standard rodent diet (Lab

Diet ® 5002 PMI Nutrition International, Brentwood, MO)

containing 201 g protein, 45 g fat, 46 g fiber, and 58 g ash per

kilogram of diet. The total metabolizable energy was 13.0 MJ

per kilogram of diet. The DR mice were fed at 16 : 00 daily.

The amount of food supplied to the DR mice was 70% of the

amount actually consumed by the AL mice. The DR mice on

Monday, Tuesday, Wednesday, and Thursday were fed with

70% of the amount consumed by the AL mice, 210% of food

was given on Friday, and 0% of that was given on Saturday and

Sunday. Both AL and DR mice had free access to water

throughout the study. The regimen was initiated at 7 weeks of

age and terminated after 24 weeks of age. From 7 through 24

weeks of age, we measured four item indices every week: time

to climb out of obstacles, time to escape restraint by gummed

tape, time hanging from a bar, and ability to resist slipping.

To measure the time to climb out of obstacles, a stainless

steel can (diameter, 17 cm; height, 22 cm) and 20000 tubular

resin chips (diameter, 0.5 cm; length, 0.5 cm; weight, 25 mg)

were used. After placing the mouse at the bottom of the can,

the can was filled with the resin chips immediately. The time it

took the mouse to climb out of the chips was measured. To

measure the time to escape restraint by gummed tape, the

abdomen of a mouse had a 5 cm wide, 15 cm length of tape

attached. The time it took for the mouse to remove the tape

was measured. To measure the bar-hanging time, the mouse

was lifted to a horizontal bar with a diameter of 2 mm and a

length of 60 cm; the mouse grasped the bar with its front paws.

The time in which the mouse was able to hang from the bar

was measured. To evaluate the ability of mice to resist

slipping, an aluminum board 40 cm long and 30 cm wide with

an angle protractor was used. We put the palms and plantae of

a mouse on the board so that its head was toward the bottom.

As the board was tilted at a sharper and sharper angle, the

mouse resisted slipping off it. When the mouse started

slipping, the angle of the board was recorded.

Figure 1 shows the body weight of AL mice and DR mice

from 7 through 24 weeks of age. The mean body weight of the

DR mice decreased from the 7th through 9th weeks of age due

to the induction of the restricted diet. Body weight began to

increase after the 10th week under the DR regimen.

Figure 2 shows changes in the time required to climb out of

the obstacles. Just after DR mice were placed in the can, they

began their climbing actions, whereas AL mice did not

immediately show such actions. As a result, after 11 weeks of

age the DR mice escaped from the obstacles in significantly

less time than did the AL mice.

Figure 3 shows changes in the time required to escape from

the tape restraint. The DR mice were significantly faster than

the AL mice from 13 through 17 weeks of age, and again from

20 through 24 weeks. At 18 weeks of age, 2 AL mice took

considerable time for escape behavior. As a result, there were

no significant differences between AL mice and DR mice at 18

weeks of age.

Figure 4 shows changes in duration of hanging from a bar.

The DR mice showed various motions to maintain a balanced

posture while hanging, whereas the AL mice seldom moved.

After 11 weeks of age, the DR mice held onto the bar

significantly longer than the AL mice did.

Figure 5 shows changes in the ability to resist slipping.

During the measurements, DR mice maintained their postures

by lowering their heads close to the aluminum board to prevent

themselves from slipping, whereas most AL mice did not

adopt such a posture. DR mice were able to stay on the board

at a significantly tighter angle than the AL mice from 11

through 17 weeks of age, from 19 through 21 weeks, and at 24

weeks.

Discussion

It has been reported that a DR regimen consisting of a 30 to

50% reduction from the average food intake of AL mice results

in a limited period of weight loss, after which the animals

maintain their body weight or gradually regain some of the

weight originally lost, despite continued dietary restriction

(Weindruch et al., 1988; Fan et al., 2001). Our results were

consistent with these previous observations.

The present study is the first report about dietary restriction

and reactions to assigned tasks in animal study. In the results,

DR mice had the advantage over AL mice in their reactions to

tasks: climbing out of obstacles, escaping from restraint by

gummed tape, hanging from a bar, and resisting slippage.

Previously, experimental data demonstrated retrogression with

age in nerve-muscle interaction, excitation-contraction

coupling, mechanical properties, and muscle energies

(Mc, 1990). The DR regimen is believed to delay these

age-related changes. In addition, Horská et al. (1999)

demonstrated that the combination of caloric restriction and

free exercise acted synergistically to decrease muscle fatigue

Ishihara, H et al. J Physiol Anthropol Appl Human Sci, 24: 209–213,

2005 211

Fig. 3 Changes in time required to escape restraint by gummed tape.

Open circles with vertical bars indicate the mean and SD of times

required to escape restraint by gummed tape of the ad libitum (AL)

mice (n 6), and closed circles of the dietary-restriction (DR) mice

(n 7). There are significant differences between DR mice and AL

mice from 13 through 17 weeks of age, and from 20 through 24

weeks.

Fig. 4 Changes in duration of hanging from a bar. Open circles with

vertical bars indicate the mean and SD of chinning times of the ad

libitum (AL) mice (n 6), and closed circles with vertical bars (n 7).

There are significant differences between DR mice and AL mice after

11 weeks of age.

Fig. 5 Changes in ability to resist slipping. Open circles with

vertical

bars indicate the mean and SD of board angles of the ad libitum (AL)

mice (n 6), and closed circles of the dietary-restriction (DR) mice

(n 7). There are significant differences between DR mice and AL

mice from 11 through 17 weeks of age, from 19 through 21 weeks,

and at 24 weeks.

Discussion

It has been reported that a DR regimen consisting of a 30 to

50% reduction from the average food intake of AL mice results

in a limited period of weight loss, after which the animals

maintain their body weight or gradually regain some of the

weight originally lost, despite continued dietary restriction

(Weindruch et al., 1988; Fan et al., 2001). Our results were

consistent with these previous observations.

The present study is the first report about dietary restriction

and reactions to assigned tasks in animal study. In the results,

DR mice had the advantage over AL mice in their reactions to

tasks: climbing out of obstacles, escaping from restraint by

gummed tape, hanging from a bar, and resisting slippage.

Previously, experimental data demonstrated retrogression with

age in nerve-muscle interaction, excitation-contraction

coupling, mechanical properties, and muscle energies

(Mc, 1990). The DR regimen is believed to delay these

age-related changes. In addition, Horská et al. (1999)

demonstrated that the combination of caloric restriction and

free exercise acted synergistically to decrease muscle fatigue

and to improve muscle force. Therefore, the advantage in their

reactions to tasks might be caused by these beneficial effects of

the DR regimen.

On the other hand, motor action arises from complex

phenomena, involving learning and the integration of past

experiences with the prediction of future conditions. It is not

the result merely of muscle force and endurance. In addition,

lighter weight in DR mice than that in AL mice might relate to

their advantage in reactions of climbing and hanging. However,

DR mice also showed advantages in the time to escape

restraint by gummed tape and in the ability to resist slipping,

and these items were not influenced by body weight.

Furthermore, in comparing with AL mice of 8 to 9 weeks of

age and DR mice of after 18 weeks, DR mice showed an

advantage in the time to escape restraint by gummed tape, the

time hanging from a bar, and the ability to resist slipping, and

both groups showed the same body weight. Therefore, the

influence of body weight might be insignificant. It can then be

considered that physical performance is affected by not only

body weight but also numerous other factors.

It is difficult to investigate these behavioral phenomena and

to explain the advantage of DR mice by using reductionistic

analysis, in which each of the phenomena presented by the

system under consideration would be divided into as many

parts as possible and analyzed separately. Therefore, in the

present study, we attempted to measure several reactions to

assigned tasks and to estimate physical performance as a total

system. However, further methodological improvement is

needed before we can analyze these reactions within specific

tasks.

In summary, we measured several reactions of mice to

assigned tasks and attempted to estimate their physical

performance. The results of the present study suggest that mice

on a restricted diet have higher physical abilities, such as those

required to avert risks to life, than ad-libitum-fed mice.

Al Pater, PhD; email: old542000@...

__________________________________________________

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