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Hi All,

See the below, which is pdf and suggests that we may retain muscle aerobic

function

in later years on CR.

Hepple RT, Baker DJ, Kaczor JJ, Krause DJ.

Long-term caloric restriction abrogates the age-related decline in skeletal

muscle

aerobic function.

FASEB J. 2005 Jun 14; [Epub ahead of print]

PMID: 15955841

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

ct & list_uids=15955841 & query_hl=2

Here is the text excerpts from the pdf. Tables 1-3 are at the end.

.... Aerobic metabolism provides the majority of ATP required by skeletal muscles

during

locomotion. Thus, it is not surprising that a decline in the capacity for

aerobic

metabolism with

aging has been linked to impaired mobility (8). Although a reduction in the

capacity

for O2

transport to skeletal muscle has been the major factor credited to account for

the

decline in the

maximal rate of aerobic metabolism (VO2max) with aging (9–11), our lab recently

showed that

even when the rate of O2 delivery is matched between age groups (using

pump-perfusion of rat

distal hindlimb muscles), there is a progressive age-related decline in skeletal

muscle mass-specific

VO2max (12, 13). This decline was particularly evident in senescent muscles

(13),

reaching ~50% of the levels observed in young adult animals, and reveals

impairment

at one or

more points in the movement of O2 from blood to cytochrome oxidase in the

mitochondria in

aging skeletal muscles. In particular, whereas the anatomic (14, 15) and

functional

capillarization

(16) are well maintained with aging in this animal model, the decline in VO2max

paralleled a

decline in mitochondrial oxidative capacity (13). Note also that the mass of the

distal hindlimb

muscles in these experiments was reduced by & #8764;50% between young adulthood

and

senescence,

which combined with the reduced mass-specific function of the skeletal muscles,

contributed to a

reduction in absolute muscle VO2max to less than one-third of the value in young

adult skeletal

muscles (13). Thus, it is clear that significant quantitative and qualitative

alterations in skeletal

muscle contribute to a markedly diminished aerobic metabolic capacity with

aging,

particularly

in senescent muscles.

Whereas aging in ad libitum (AL) fed animals is characterized by the

aforementioned

decline in

skeletal muscle mass and function, long-term CR markedly attenuates some of

these

changes. In

particular, previous studies have shown that long-term CR in rodents (i.e., that

instituted in

juvenile animals) attenuates the loss of muscle mass (5–7). Furthermore, recent

reports show that

CR is effective in preventing the decline in force per cross-sectional area

normally

seen with

aging in skeletal muscle (17, 18). ... That CR might

be beneficial in maintaining skeletal muscle aerobic function is supported by

the

observations

that long-term CR slows the progression of mitochondrial abnormalities, such as

altered

proportionality between individual complexes of the electron transport chain

(19)

and the

accumulation of cytochrome oxidase deficient fibers (6, 20), in aged muscles.

Gene

microarray

studies examining the molecular basis of CR’s protective effects show that CR

attenuates most of

the age-related changes seen in skeletal muscle (21, 22) and cardiac muscle (23)

of

AL animals,

including maintaining the expression of genes related to muscle mitochondrial

energy

metabolism. In this regard, although two recent studies have suggested that CR

does

not prevent

the decline in skeletal muscle oxidative capacity with aging (22, 24), these

studies

did not have a

young adult CR control group. This point is important because an earlier study

showed in mouse

skeletal muscles that, although oxidative capacity was lower in young adult

animals

subjected to

CR, the decline in oxidative capacity with aging was prevented by CR in mice up

to

20 months

of age (19).

.... In the AL-fed group animals were selected to represent young adult (8–10

month

old; ~100%

survival rate) and senescent (35–36 month old; & #8764;35% survival rate)

animals,

based upon

previously published survival curves for this rat strain (2). In the CR group we

studied 8–10 mo

old and 35 mo old animals. CR was imposed beginning at 14 weeks of age, such

that by

the age

of 16 weeks the animals were receiving 40% lower caloric intake than AL animals,

and

this was

maintained until the animals were studied in our lab. Note that, although total

caloric intake was

reduced in the CR group, the feed was supplemented (NIH 31 fortified) with

vitamins

and other

nutrients to maintain adequate nutrition in these animals.

.... Whereas the AL fed animals were provided rat

chow (NIH31) ad libitum, CR animals were provided with supplemented rat feed

(NIH31-NIA

fortified) and maintained on the CR diet (40% lower caloric intake).

.... RESULTS

General animal characteristics

The AL rats were heavier than the CR rats, regardless of age (Table 1). On the

other

hand,

although the mass of the distal hindlimb muscles was less in the 8 mo old CR vs.

8–10 mo old

AL rats, by 35 months of age the mass of these muscles (with the exception of

soleus

muscle)

was greater in the CR vs. AL rats because of a markedly attenuated rate of

muscle

atrophy with

aging in the CR animals. Notwithstanding this point, irrespective of dietary

treatment, the

greatest muscle mass decline was evident in the gastrocnemius muscle,

intermediate

in plantaris

muscle, and least in soleus muscle. Similar to the differences with aging and/or

CR

seen in the

distal hindlimb muscles, the total hindlimb muscle mass declined markedly

between

8–10

months and 35 months of age in AL animals, and this was attenuated by CR.

Metabolic and contractile responses

One of the 35 mo old CR animals died during surgical preparation of the hindlimb

for

pump-perfusion.

Thus, metabolic and contractile data for the 35 mo old CR group are based upon 5

animals.

Table 2 shows that muscle mass-specific blood flow, arterial O2 content and

muscle

convective

O2 delivery (convective O2 delivery = arterial O2 content × blood flow) were

well

matched

between all groups during the pump-perfusion experiments. As seen previously,

resting VO2 was

not affected by age (13) and was not affected by dietary treatment (Table 3).

Similar to our

previous results (32), there was a marked decline in the peak tension responses

in

the 35 month-ld

vs. 8–10 mo old AL animals, and this persisted after normalizing forces to the

mass

of the

gastrocnemius, plantaris, soleus muscle group (Table 3, Fig. 1). In contrast,

although there was a

modest reduction in absolute peak tension in the 35 mo old vs. 8–10 mo old CR

animals, this

difference was abolished after normalizing to the mass of the gastrocnemius,

plantaris, soleus

muscle group.

Consistent with our prior results (13), both VO2max and peak lactate efflux were

markedly

reduced between 8–10 mo old and 35 mo old AL animals (Table 3, Fig. 2 and Fig.

3).

This

difference persisted after accounting for the smaller muscles in the aged

animals.

In contrast,

although there were modest reductions in absolute VO2max and peak lactate efflux

with aging in

CR animals, normalizing to the muscle mass abolished the decline in VO2max and

reduced the

age-related decline in lactate efflux to 18% in 35 mo old CR animals. In other

words, the decline

in absolute VO2max with aging in CR animals was entirely due to less muscle (no

reduced muscle

function), which is in stark contrast to the AL animals where both a loss of

muscle

and reduced

mass-specific muscle function played a significant role in accounting for the

reduced absolute

VO2max responses with aging.

Muscle oxidative capacity

Note that the units in Fig. 4 refer to the rate of appearance of the mercaptide

ion

(citrate

synthase), the rate of appearance of reduced cytochrome c (complex I-III), or

the

rate of

appearance of oxidized cytochrome c (complex IV). Similar to our previous

results in

plantaris

muscle (13), aging in AL animals resulted in a marked reduction in oxidative

capacity in

plantaris muscle and the mixed region of gastrocnemius muscle. In the plantaris

muscle this

reduction was of similar magnitude (38–41%) for citrate synthase, complexes

I–III,

and complex

IV. On the other hand, in the mixed region of gastrocnemius muscle the decline

in

activity of

citrate synthase and complexes I–III with aging in AL animals was not

statistically

significant

(19 and 29%, respectively; Holm-Sidak unadjusted P=0.012 with a critical P of

0.010,

and

unadjusted P=0.027 with a critical P of 0.009, respectively), whereas the

reduction

in complex

IV activity with aging in AL animals was similar in mixed gastrocnemius muscle

(39%)

to that

observed in plantaris muscle (41%). In contrast to these results, CR rats

exhibited

no decline in

oxidative capacity with aging, regardless of the muscle considered. It is also

relevant that for

citrate synthase activity and complex IV activity, the 8–10 mo old CR animals

actually started at

a lower point, but maintained this level with age. Note that muscle protein

concentration

assessment in the gastrocnemius muscle revealed that although there was no

difference between

8–10 mo old AL (376±4 µg protein·mg muscle –1 ), 8–10 mo old CR (367±10 µg

protein•mg

muscle –1 ) and 35 mo old CR (359±8 µg protein·mg muscle –1 ) rats, protein

concentration was

10% lower in 35 mo old AL (339±17 µg protein·mg muscle –1 ) than 8–10 mo old AL

rats. Thus, a

small portion of the age-related decline in oxidative capacity in AL animals can

be

ascribed to a

dilution of muscle protein rather than a loss of mitochondria per se.

Complex IV activity in situ

To estimate the oxygen flux through complex IV in situ at VO2max in our

pump-perfusion

experiments, we calculated the mass-adjusted activity of complex IV in the

plantaris

and mixed

gastrocnemius muscle (which comprise & #8764;50% of the contracting muscles by

mass)

as a whole

and then took the quotient of VO2max and this aggregate complex IV activity.

This

calculation

revealed a significant main effect for a higher oxygen flux through complex IV

at

VO2max in the

mitochondria of CR animals that was not dependent upon age (no age × diet

interaction), despite

matching the rate of muscle convective oxygen delivery between groups. As such,

this

provides

evidence that mitochondria from CR animals have a higher affinity for oxygen in

situ.

DISCUSSION

The current results show that, in contrast to the marked (46%) decline in

mass-specific VO2maxin

the distal hindlimb skeletal muscles with aging in AL animals, not only did CR

animals begin at

the same point as AL animals in young adulthood, but CR completely prevented the

decline in

mass-specific skeletal muscle VO2maxwith aging. In addition, whereas the decline

in

VO2max with

aging in AL animals paralleled a decline in muscle oxidative capacity

(particularly

complex IV),

in CR animals citrate synthase and complex IV activities began at lower levels

and

there was no

age-related decline in any marker of oxidative capacity. Furthermore, CR also

prevented the

disproportionate alterations of in vitro citrate synthase activity and complex

IV

activity seen in

AL animals with aging in the mixed region of gastrocnemius muscle. Lastly, the

estimated

oxygen flux through complex IV in situ at VO2max in the distal hindlimb muscles

of

CR animals

was higher than that of AL animals, despite a similar rate of muscle oxygen

delivery, suggesting

a higher oxygen affinity in CR mitochondria. As such, these results demonstrate

that

CR

prevents the decline in mass-specific aerobic function between young adulthood

and

senescence

in large part by preventing the age-related decline in mitochondrial oxidative

capacity and by

facilitating superior mitochondrial function in situ.

Effect of aging and/or CR on skeletal muscle contractile and metabolic

performance

In recent experiments from our lab, we used a pump-perfused model to overcome

the

limitation

imposed on contracting skeletal muscles by the reduction in convective O2

delivery

seen in vivo

with aging (11, 33, 34). These experiments showed a progressive decline in

skeletal

muscle

VO2maxwith aging in AL animals even when the aged muscles were provided with the

same rate

of convective O2 delivery (12, 13), revealing impairment in aerobic capacity

within

the aging

muscles.

Previous studies have shown that CR slows the decline in skeletal muscle mass

and

contractile

function that normally accompanies aging (5, 17, 18, 35). Specifically, CR

attenuates the loss of

muscle mass with aging, primarily by preventing the loss of muscle fibers (5–7).

In

addition, CR

prevents the fall in skeletal muscle specific force (i.e., force per

cross-sectional

area) in both 33

mo old F344BN rats (17), and in 26–28 mo old Fischer 344 rats (18). Thus, our

results, showing

that CR prevented the mass-specific decline in force generating capacity of the

gastrocnemius-plantaris-

soleus muscle group between 8–10 mo and 35 mo of age in F344BN rats, are similar

to

the aforementioned studies (17, 18). Note that denervation is unlikely to

explain

the mass-specific

force deficit in 35 mo old AL animals, as Brown and Hasser previously

demonstrated

no

difference in twitch forces generated by direct muscle stimulation vs. that seen

with nerve

stimulation in soleus, extensor digitorum longus and plantaris muscles of 36 mo

old

male

F344BN rats (36). We have confirmed these findings in our lab and see no

difference

in peak

twitch forces under supramaximal stimulation conditions (0.05 s pulses at >20 V

for

direct

muscle stimulation) between sciatic nerve stimulation (2.4±0.3 N) vs. direct

end-to-end muscle

stimulation (2.5±0.3 N) of the gastrocnemius-plantaris-soleus muscle group in 35

mo

old male

F344BN rats (R.T. Hepple and D.J. Baker, unpublished results). Thus, the

protection

of specific

force by CR is not due to its preservation of motor neuron number (37).

The potential benefit of CR on skeletal muscle aerobic performance has not been

examined

previously. Our results showed that whereas muscle mass-specific VO2max declined

by

46%

between 8–10 mo and 35 mo of age in AL animals, CR animals not only started at

the

same level

at 8–10 mo of age, but CR completely prevented the age-related decline of muscle

mass-specific

VO2max up to 35 mo of age (senescence for AL animals). In addition to

maintaining

muscle

quality, CR markedly attenuated the degree of atrophy in the distal hindlimb

muscles

(21%) vs.

that seen in 35 mo old AL animals (50%), such that there was only a modest

decline

in absolute

VO2max (22%) compared with the severe reduction seen in AL animals (72%). Thus,

CR

preserves skeletal muscle aerobic function not only by preserving the

muscle-mass

specific

function, but also by markedly attenuating the age-related loss of muscle mass.

Since CR animals

exhibit a longer life span than AL animals, it would have been valuable to

include

CR animals at

a similar relative survival rate as 35 mo old AL animals (i.e., a 40 mo old CR

group). However,

it was not possible to include this group in our current results because in

preliminary studies we

found that the 40 mo old CR rats did not tolerate the sodium pentobarbital

anesthesia employed

in the other groups (3 out of 4 animals died prior to establishing hindlimb

perfusion; R.T.

Hepple, unpublished results).

We have previously noted a reduced capacity to generate lactate in aged muscles

of

F344BN rats

(32), consistent with experiments using nuclear magnetic resonance spectroscopy

that

indicate a

reduced glycolytic metabolism in the calf muscles of older exercising humans

(38),

which is

similar to the decline of aerobic function with aging. The current results

confirm

our previous

findings in AL animals and show that in contrast, CR largely maintains the

capacity

for

generation of lactate during intense muscle contractions, suggesting CR helps

preserve glycolytic

capacity with aging. Thus, taken collectively, our results show that CR is

highly

effective not

only in slowing the quantitative loss of muscle, but is even more effective in

maintaining muscle

contractile and metabolic function (i.e., maintained ATP generating capacity)

with

aging.

Basis for the preserved aerobic metabolic response in aging muscles by CR

As noted previously (13), the principle factors that could account for a

reduction

in muscle mass-specific

VO2max in aged muscles pump-perfused at similar rates of convective O2 delivery

as

muscles from young adult animals are a reduced anatomic and/or functional

capillary

surface

area, and a reduced oxidative capacity. In addressing these factors, we and

others

have shown

that neither the anatomic (14, 15) nor the functional capillary surface area

(16)

appears to be

altered with aging in the skeletal muscles of the F344BN rat. On the other hand,

there is a decline

in mitochondrial oxidative capacity that is proportional to the decline in

mass-specific VO2max

with aging (13). The current results in AL animals are similar in this context

in

that a 46%

decline in skeletal muscle mass-specific VO2max seen between 8–10 mo old and 35

mo

old AL

animals was accompanied by a & #8764;40% decrease in the in vitro activity of

complex

IV (i.e., the

component of the electron transport chain where O2 is used as the terminal

electron

acceptor) in

plantaris muscle and mixed region of gastrocnemius muscle. On the other hand,

the

maintained

levels of oxidative capacity with aging by CR aids significantly in preventing

the

fall of muscle

mass-specific VO2max in these animals, although a contribution by other factors

not

quantified in

our study cannot be ruled out.

CR has proven effective in protecting mitochondrial oxidative capacity and

function

with aging

in liver (39) and skeletal muscle (19). In contrast to this view, however, two

recent studies

appear inconsistent with the idea that CR protects oxidative capacity in aged

skeletal muscles. In

one of these studies (22), male 12-week-old Sprague-Dawley rats were put onto a

40%

CR diet

(i.e., energy intake reduced to 60% of AL, as done here) for 36 weeks. After 36

weeks these

investigators reported no difference in citrate synthase activity or maximal

mitochondrial ATP

production rate in gastrocnemius muscles of control vs. CR animals (22).

Similarly,

Drew and

colleagues showed no difference in maximal mitochondrial ATP production rate in

gastrocnemius muscles from 26 mo old AL vs. 26 mo old CR Fischer 344 rats (24).

In

contrast to

these findings, however, a prior study by Desai and colleagues showed that,

whereas

the

gastrocnemius muscle from AL fed mice exhibited a 54–74% decline in the

activities

of

individual components of the electron transport chain with aging, CR completely

opposed these

changes (19). Although these latter findings may appear to be contradicted by

the

more recent

studies noted above (22, 24), the study by Desai and colleagues (19) included a

young CR

control group and it is noteworthy that the young CR animals had lower

activities of

the electron

transport chain complexes than did young AL fed animals. Our current results

confirm

the results

of Desai and colleagues (19) and show that CR does indeed prevent the

age-related

loss of

skeletal muscle mitochondrial oxidative capacity, but that the young CR animals

start out at a

significantly lower point, such that only comparing the older animals would lead

one

to

mistakenly conclude that CR did not prevent the age-related decline in oxidative

capacity.

Further to this point, despite the lower oxidative capacity in young adult CR

animals, there was

no deficit in muscle VO2max vs. the young adult AL animals. Since the oxygen

delivery was

matched between these groups, these results suggest that mitochondria from CR

animals have a

higher affinity for oxygen than AL animals. This possibility is backed up by the

significant main

effect for a higher rate of oxygen flux per unit of complex IV activity in the

muscles of CR

animals (as estimated from the quotient of VO2max and complex IV activity; see

next

section). On

the other hand, it might be considered that the lower oxidative capacity

observed in

the muscles

of the young adult CR animals might have imposed a limitation to aerobic

function

had the rate

of blood flow, and thus oxygen delivery, been higher. Note that the rate of

skeletal

muscle blood

flow during high-velocity treadmill running in rats (40) is considerably higher

than

that possible

with the pump-perfused rat hindlimb model (due to the inability of increasing

flow

further

without incurring damaging levels of perfusion pressure), lending support to the

possibility that

CR rats might exhibit lower VO2max values during whole body maximal exercise. To

our

knowledge, the maximal running capacity of CR animals has not been examined,

precluding

assessment of this possibility at this time.

Effect of caloric restriction on mitochondrial function

CR may maintain mitochondrial oxidative capacity with aging by preserving

mitochondrial

quality and/or mitochondrial content. In the current experiments CR prevented

the

age-related

decline in all three markers of oxidative capacity (citrate synthase, complexes

I–III, and complex

IV) in senescent F344BN rats, similar to prior results in aged mice (19). It is

not

possible, based

upon the current analysis, to distinguish the extent to which the decrease in in

vitro muscle

oxidative capacity of 35 mo old AL animals was due to a reduced quantity vs.

quality

of

mitochondria. In other words, even though our in vitro assays indicated a

reduced

oxidative

capacity with aging in AL fed rats, this age effect could reflect impaired

enzyme

function rather

than reduced enzyme content per se. In support of the latter possibility, Bota

and

colleagues

recently found that although aconitase activity declined significantly with

aging in

mouse

skeletal muscles, this was not accompanied by a reduction in aconitase protein

content (41).

Furthermore, a recent report showed that mitochondrial volume density in the

extensor digitorum

longus muscle and the soleus muscle was not altered between 12 months and 35

months

in AL

fed male F344BN rats (14), which is the same strain of rat studied here. Thus,

we

cannot discern

at this time whether the protection of these enzyme activities by CR was due in

part

to a

protection of mitochondrial content.

On the other hand, we have several lines of evidence to indicate that CR

protected

mitochondrial

function. First, the relatively greater decline in activity of complex IV than

other

mitochondrial

enzymes often seen in aged muscles (19, 42, 43), and evident in the mixed region

of

the

gastrocnemius muscle in the 35 month old animals of the current study, was

prevented

by CR.

Similar benefits of CR on age-related changes in mitochondrial enzymes have been

seen

previously in aged mice (19, 44) and rats (20, 44). The second line of evidence

supporting a

beneficial effect of CR on mitochondrial function in our study is the

aforementioned

higher in

situ rate of complex IV turnover at VO2max seen in CR animals. In this regard, a

previous study

observed that complex IV in gastrocnemius muscle mitochondria from CR mice had a

higher

proportion of high affinity binding sites (80%) than mitochondria from AL mice

(69%)

in young

animals. Furthermore, CR prevented the decline in the proportion of

high-affinity

binding sites

for cytochrome c in complex IV with aging (19). Desai and colleagues stated that

maintaining a

higher proportion of high-affinity binding sites in complex IV with aging would

permit a higher

rate of complex IV activity for a given concentration of cytochrome c (19).

Thus,

our results

showing that the oxygen flux through complex IV at VO2max in situ was

significantly

higher in

muscles from CR than AL rats, despite conditions where oxygen availability is

expected to be

similar (muscle mass-specific convective O2 delivery was matched between

groups), is

consistent with a higher affinity of complex IV for O2 in the mitochondria of

the CR

vs. AL

animals. As such, these results show that CR promotes a superior function of

complex

IV in situ,

and that this in part contributes to the maintenance of skeletal muscle aerobic

function with aging

by CR. It should also be noted that maintaining a high proportion of

high-affinity

binding sites in

complex IV with aging is thought to lower the rate of free radical production

(45),

which has

been hypothesized to account for some of the protective effects of CR on tissue

and

organism

aging (19, 46, 47).

Role of voluntary physical activity in the effect of caloric restriction

Early work by Goodrick (48) suggested that some of the protective effects of CR

on

longevity

were due to sustained high levels of voluntary physical activity. It may be

relevant, therefore,

that in previous studies we saw a significant decline in the volume of daily

voluntary physical

activity with aging in AL fed F344BN rats under cage-confined conditions (13).

Although

variation in voluntary physical activity may play a role in the decrease of

mitochondrial

oxidative capacity with aging and its protection by CR, several lines of

evidence

argue against

this being the sole explanation. First, whereas mitochondrial enzyme proportions

are

maintained

across wide ranges of oxidative capacity between sedentary and trained animals

(49),

the

reduction in oxidative capacity in aged muscles is often characterized by a

disproportionate

reduction in complex IV activity (e.g., the mixed region of gastrocnemius muscle

in

the current

study and 19, 43), and CR retards this change (current results; 6, 19, 20).

Second,

whereas CR

promotes increases in both mean and maximal life span (50, 51), voluntary

exercise

increases

mean life span only (50, 52, 53). As such, the available evidence indicates that

CR

operates

through mechanisms that are distinct from physical activity in its effects on

life

span and

mitochondrial function. Notwithstanding this point, it would be valuable to

compare

the

protection of skeletal muscle aerobic performance and mitochondrial oxidative

capacity by CR

vs. that obtained by physical activity to provide a clearer understanding of the

different

mechanisms involved.

The current results show that CR completely prevents the nearly 50% decline in

mass-specific

skeletal muscle VO2max between young adulthood and senescence in AL fed F344BN

rats.

This

effect is due to a maintained mitochondrial oxidative capacity with aging by CR,

acting in

conjunction with a higher in situ oxygen affinity of complex IV that permits

similar

aerobic

function at a lower level of oxidative capacity in young adult animals. Our

results

also clarify

previous controversy regarding the effect of CR on mitochondrial oxidative

capacity

with aging

by showing that although there may be no difference between AL vs. CR in aged

animals; the

CR animals start at a lower point in young adulthood and do not decline with

age. As

such, the

current results show that in addition to the previously established slowing of

muscle atrophy with

aging, CR has an even more profound effect in maintaining skeletal muscle

contractile and

aerobic metabolic function.

Table 1

Descriptive data

----------------------------------

8–10 mo old AL 35 mo old AL 8–10 mo old CR 35 mo old CR

----------------------------------

Body Mass, g 443±7 471±26 326±6 † ,‡ 319±7 ‡

Soleus mass, mg 173±3 104±3* 136±5 † ,‡ 114±5*

Plantaris mass, mg 418±8 193±20* 326±7 † ,‡ 261±17* ,† ,‡

Gastrocnemius mass,mg 2190±43 877±89* 1649±53 † ,‡ 1189±77* ,† ,‡

Distal hindlimbmuscle mass, g 5.04±0.16 2.52±0.24* 3.86±0.12 † ,‡ 3.09±0.12* ,†

,‡

Total hindlimb musclemass, g 18.36±0.40 13.29±0.45* 13.98±0.24 † 11.32±0.56* ,†

,‡

-------------------------------------

Values are means±SE; mo = months; AL = ad libitum fed; CR = caloric restricted.

*P <

0.05 versus 8–10 mo old of same dietary treatment. † P <

0.05 versus age-matched ad libitum group. ‡ P < 0.05 versus 35 mo old AL.

Table 2 Perfusion Conditions

---------------------------------------

8–10 mo old AL 35 mo old AL 8–10 mo old CR 35 mo old CR

---------------------------------------

Total perfusion pressure,Torr 135±8 96±8* 134±2 126±7†

Net perfusion pressure,Torr 87±6 62±6* 90±2 84±2†

Hindlimb blood flow,ml·min–1 10.4±0.1 6.3±0.5* 7.9±0.1† 7.3±0.1

Muscle blood flow,ml·min–1·100 g–1 79±7 84±6 75±6 76±8

Arterial O2 content,volume % 21.6±0.4 21.8±0.5 22.3±0.5 22.7±0.4

Muscle QO2,µmol·min –1·100 g –1 662±56 721±30 640±38 668±73

---------------------------------------

Values are means±SE. AL = ad libitum fed. CR = caloric restricted. QO2 =

convective

O2 delivery (arterial O2 content × blood flow). *P < 0.05

versus 8–10 mo old of same dietary treatment. † P < 0.05 versus age-matched ad

libitum group.

Table 3 Contractile and metabolic responses

-------------------------------

8–10 mo old AL 35 mo old AL 8–10 mo old CR 35 mo old CR

-------------------------------

Resting VO2,µmol·min –1 7.2±0.6 4.1±0.6* 4.9±0.5† 4.1±0.5

Resting VO2,µmol·min –1·100 g–1 39±4 31±5 33±3 36±5

Peak force,N 34.9±4.7 7.9±1.5* 27.6±2.1 21.0±0.7*,†

Peak force,N·g-1 12.9±2.1 6.5±1.0* 13.2±1.3 13.9±0.8†

Force at VO2maxN 13.0±1.9 3.1±0.6* 10.9±0.8 7.2±0.3*,†

Force at VO2maxN·g -1 4.8±0.8 2.5±0.4* 5.2±0.4 4.8±0.5†

Peak lactate efflux,µmol·min –1 43.0±3.1 8.0±1.9* 34.9±2.4† 23.0±2.3*,†

Peak lactate efflux,µmol·min–1 ·100 g –1 879±72 307±59* 900±69 740±58*,†

VO2max,µmol·min –1

26.3±1.5 7.3±1.6* 19.1±1.6† 14.9±1.7*,†

VO2max,µmol·min –1·100 g–1 524±13 281±54* 490±42 484±49

------------------------------------------

† Values are means±SE. AL = ad libitum fed. CR = caloric restricted. QO2 =

convective O2 delivery (arterial O2 content × blood flow). *P < 0.05

versus 8–10 mo old of same dietary treatment. † P < 0.05 versus age-matched ad

libitum group.

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

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