Guest guest Posted June 16, 2005 Report Share Posted June 16, 2005 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@... __________________________________________________ Quote Link to comment Share on other sites More sharing options...
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