Biomedical subjects

Russell T Hepple

Publications and source records attributed to Russell T Hepple.

At least 19 recordsLinked to original sources

PubMed2006

Elevated caspase and AIF gene expression correlate with progression of sarcopenia during aging in male F344BN rats.

To establish the relationship between the progression of sarcopenia and apoptosis we examined apoptotic gene expression in plantaris muscles (Pl) from 8 mo old (n=8), 30 mo old (n=8) and 35 mo old (n=6) male rats by real-time PCR. Pl mass declined from 368 +/- 7 mg at 8 mo to 333 +/- 7 mg at 30 mo (P<0.05) and 210 +/- 15 mg at 35 mo of age (P<0.05). BAX, Bcl-2, and Apaf-1 expression decreased by 62-74% at 30 mo and by 90-96% at 35 mo of age (all P<0.05 vs 8 mo old). In contrast, the expression of Caspases 3, 8, and 9 and AIF increased 3- to 5-fold at 30 mo (NS) and 7- to 50-fold at 35 mo of age (P<0.05). There were significant (P<0.05) correlations between Pl mass and Caspase 3 (r(2)=-0.60), Caspase 9 (r(2)=-0.58), Caspase 8 (r(2)=-0.50), and AIF (r(2)=-0.48). Thus, our results show that the expression of some genes involved in apoptosis increase with aging in Pl and correlate with progression of sarcopenia (Caspase 3, Caspase 9, Caspase 8, and AIF), whereas others decline with aging (BAX, Bcl-2, and Apaf-1).

Aging↗

PubMed2006

Differential sensitivities of cerebral and brachial blood flow to hypercapnia in humans.

Although it is known that the vasculatures of the brain and the forearm are sensitive to changes in arterial Pco(2), previous investigations have not made direct comparisons of the sensitivities of cerebral blood flow (CBF) (middle cerebral artery blood velocity associated with maximum frequency of Doppler shift; Vp) and brachial blood flow (BBF) to hypercapnia. We compared the sensitivities of Vp and BBF to hypercapnia in humans. On the basis of the critical importance of the brain for the survival of the organism, we hypothesized that Vp would be more sensitive than BBF to hypercapnia. Nine healthy males (30.1 +/- 5.2 yr, mean +/- SD) participated. Euoxic hypercapnia (end-tidal Po(2) = 88 Torr, end-tidal Pco(2) = 9 Torr above resting) was achieved by using the technique of dynamic end-tidal forcing. Vp was measured by transcranial Doppler ultrasound as an index of CBF, whereas BBF was measured in the brachial artery by echo Doppler. Vp and BBF were measured during two 60-min trials of hypercapnia, each trial separated by 60 min. Since no differences in the responses were found between trials, data from both trials were averaged to make comparisons between Vp and BBF. During hypercapnia, Vp and BBF increased by 34 +/- 8 and 14 +/- 8%, respectively. Vp remained elevated throughout the hypercapnic period, but BBF returned to baseline levels by 60 min. The Vp CO(2) sensitivity was greater than BBF (4 +/- 1 vs. 2 +/- 1%/Torr; P < 0.05). Our findings confirm that Vp has a greater sensitivity than BBF in response to hypercapnia and show an adaptive response of BBF that is not evident in Vp.

Adult↗

PubMed2006

Nitric oxide synthase inhibition reduces O2 cost of force development and spares high-energy phosphates following contractions in pump-perfused rat hindlimb muscles.

The purpose of the present experiments was to test the hypotheses that: (i) nitric oxide synthase (NOS) inhibition reduces the O2 cost of force development across a range of contractile demands; and (ii) this reduced O2 cost of force development would be reflected in a sparing of intramuscular higher energy phosphates. Rat distal hindlimb muscles were pump perfused in situ and electrically stimulated (200 ms trains with pulses at 100 Hz, each pulse 0.05 ms duration) for 1 min each at 15, 30 and 60 tetani min(-1) and for 2 min at 90 tetani min(-1) in three groups: 0.01 mM adenosine; 1 mM D-NAME and 0.01 mM adenosine (D-NAME); and 1 mM L-NAME and 0.01 mM adenosine (L-NAME). The gastrocnemius-plantaris-soleus muscle group was freeze clamped post-contractions for metabolite analyses. Force was 19% higher and oxygen uptake (VO2) was 20% lower with L-NAME versus adenosine, and there was a 35% reduction in VO2/time-integrated tension versus adenosine and 24% versus D-NAME that was independent of contraction frequency. L-NAME treatment produced a 33% sparing of muscle phosphocreatine (PCr), and intramuscular lactate was no different between groups. In contrast, D-NAME reduced force by 30%, VO2 by 29% and the O2 cost of force development by 15% compared with adenosine, but had no effect on the degree of intramuscular ATP and PCr depletion. These results show that NOS inhibition improved the metabolic efficiency of force development, either by improving the ATP yield for a given O2 consumption or by reducing the ATP cost of force development. In addition, these effects were independent of contraction frequency.

Adenosine↗

PubMed2006

Dividing to keep muscle together: the role of satellite cells in aging skeletal muscle.

The factors responsible for the atrophy of skeletal muscle with aging remain to be elucidated. Recent evidence points toward an important role for a population of cells located on the surface of skeletal muscle fibers, known as satellite cells, in maintaining the integrity of skeletal myocytes throughout the life span. This Perspective examines the role that these cells are thought to play in aging muscle atrophy, and highlights a recent study by Brack and colleagues that attempts to understand the role of satellite cells in maintaining the ratio of myonuclear number to cytoplasmic volume within myocytes as we age.

Aging↗

PubMed2006

Caloric restriction protects mitochondrial function with aging in skeletal and cardiac muscles.

In skeletal muscles and heart in vitro complex IV activity is lower in young adult caloric restricted (CR) animals despite normal aerobic function in situ and in vivo. On the other hand, whereas markers of oxidative capacity decline 25% to 46% between 8 and 10 months and 35 months in ad libitum fed (AL) animals, in most muscles there is no decline in CR across the same absolute age (35 mo old) or relative age (35% survival rate) span and PGC-1alpha gene expression in gastrocnemius muscle declines more slowly with aging. The present results show that CR largely prevents the age-associated decline in mitochondrial function in heart and skeletal muscles, and suggest that this is secondary to a better-maintained drive on mitochondrial biogenesis.

Aging↗

PubMed2006

No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: effects are independent of mitochondrial DNA integrity.

We investigated if calorie restriction (CR) preserved skeletal muscle oxidative capacity with aging after accounting for life span extension by CR, and determined if mitochondrial content, mitochondrial DNA integrity, and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) were involved. Ad libitum-fed (AL) and CR animals representing young adult, late middle age, and senescence were studied. Whereas citrate synthase and complex IV activities were lower in plantaris and gastrocnemius muscle of young adult CR animals, in contrast to the 15%-40% decline in senescent AL animals, there was no decline with aging in CR animals. There was no decline in citrate synthase protein in gastrocnemius with aging in either group, suggesting that CR preserves oxidative capacity with aging by protecting mitochondrial function rather than content. This protection was independent of mitochondrial DNA damage between groups. However, there was a slower decline in PGC-1alpha gene expression with aging in CR versus AL animals, suggesting a better maintenance of mitochondrial biogenesis with aging in CR animals.

Aging↗

PubMed2005

Nitric oxide synthase inhibition reduces the O2 cost of force development in rat hindlimb muscles pump perfused at matched convective O2 delivery.

Nitric oxide (NO) is a physiological mediator of skeletal muscle function. Specifically, NO affects cellular respiration and muscle contractility; however, the reduced blood flow and convective O2 delivery that result from impaired vasodilatation when NO synthase (NOS) is inhibited in vivo have obscured past interpretations of the effects of NO. Therefore, we studied the effect of NOS inhibition in an in situ pump-perfused rat hindlimb to test the hypothesis that NOS inhibition would improve contractile and aerobic metabolic performance. Pump perfusion permitted matching of convective O2 delivery (516 +/- 16 micromol O2 min(-1) (100 g)(-1); mean +/- s.e.m.) between groups, allowing us to investigate the effects of NOS inhibition independent of this variable. Three groups were studied. The perfusate of one group was treated with both adenosine (0.01 mm) and the NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 mm). Adenosine is a vasodilator that can act through both NO-dependent and -independent pathways; the NO-independent vasodilatory action of adenosine allowed us to match the perfusion rate and convective O2 delivery in this L-NAME group to those of the other groups. In the second group the perfusate was treated with adenosine only (Ado). In the third group the perfusate received no treatment and served as a control (Con). Oxygen consumption (VO2) was on average 26 and 14% lower during the contraction bout in L-NAME and Ado, respectively, versus Con. In Ado, lactate efflux was similar to Con and force was reduced in proportion to versus Con, whereas L-NAME was associated with a 32% lower lactate efflux and similar force to Con. Therefore, the lower :force development ratio in the L-NAME group demonstrates that the O2 cost of force development is reduced by NOS inhibition independent of convective O2 delivery.

Adenosine↗

PubMed2005

Long-term caloric restriction abrogates the age-related decline in skeletal muscle aerobic function.

The purpose of this study was to determine the effect of long-term caloric restriction (CR) on the age-associated decline of skeletal muscle aerobic function. Skeletal muscle maximal aerobic performance (VO2max) was assessed in ad libitum (AL) and CR rats aged 8-10 months and 35 months using a pump-perfused hindlimb model to match oxygen delivery to muscle mass between groups. Whereas there was a 46% decline in muscle mass-specific VO2max between 8-10 mo (524+/-13 micromol x min(-1) x 100 g(-1); mean+/- SE) and 35 mo (281+/-54 micromol x min(-1) x 100 g(-1)) in AL rats, not only did CR rats begin at the same point in 8-10 mo old rats (490+/-42 micromol x min(-1) x 100 g(-1)), we found no decline in 35 mo old CR animals (484+/-49 micromol x min(-1) x 100 g(-1)). Interestingly, although most markers of oxidative capacity began at a lower point in young adult CR animals, CR rats exhibited a higher in situ activity of complex IV at VO2max. This activity allows the young adult CR animals to exhibit normal aerobic capacity despite the lower oxidative enzyme activities. In stark contrast to the 19-41% decline in activities of citrate synthase, complexes I-III, and complex IV in homogenates prepared from the plantaris muscle and mixed region of gastrocnemius muscle with aging in AL rats, no age-related decline was found in CR animals. Thus, our results showed that CR preserves aerobic function in aged skeletal muscles by facilitating a higher in situ function of complex IV and by preventing the age-related decline in mitochondrial oxidative capacity.

Aerobiosis↗

PubMed2005

The versatility of the pump-perfused rat hindlimb preparation: examples relating to skeletal muscle function and energy metabolism.

The pump-perfused rat hindlimb model, in various forms, has been in use for several decades. There are many applications for this model, owing to the ability to control the content and rate of perfusion. In the context of exercise physiology this model has been put to particularly good use. In this report we summarize some of the central surgical differences between different versions of the pump-perfused rat hindlimb model, including the double hindlimb + trunk, double hindlimb alone, single hindlimb, and distal hindlimb-alone models. We also summarize specific elements of the perfusion medium and measurement of force used in our lab during assessment of muscle metabolic and contractile responses, and illustrate some of the differences from the in vivo condition that merit consideration. We then provide specific examples of how the single pump-perfused hindlimb and distal hindlimb-alone versions of this model have been used to study muscle function and energy metabolism. In this context we show how this model can be used to permit the experimenter to manipulate and control the rate of O(2)delivery and to add specific compounds that inhibit a particular aspect of muscle metabolism, such that in combination with measurements of the flux of specific substances across the muscle and/or fast-freezing of muscle after contractions, more can be understood about the metabolic state of the contracting muscles.

Animals↗

PubMed2004

Anatomic capillarization is maintained in relative excess of fiber oxidative capacity in some skeletal muscles of late middle-aged rats.

The anatomic size of the capillary-to-fiber (C/F) interface plays an important role in O(2) flux from blood to tissue by determining the surface area available for diffusion and is maintained in relative proportion to fiber mitochondrial volume across a wide range of muscle aerobic capacity. In the present study, we examined an estimate of the anatomic size of the C/F interface [the quotient of the individual C/F ratio and fiber perimeter, C/F perimeter exchange (CFPE) index] and fiber oxidative capacity in different skeletal muscles, or muscle regions, to test the hypothesis that capillarization would be maintained in relative excess of reduced fiber oxidative capacity in aged muscles. The right gastrocnemius, plantaris, and soleus muscles from young adult (8 mo old) and late middle-aged (28-30 mo old) Fischer 344 x Brown Norway F1 hybrid rats were excised for evaluation of flux through electron transport chain complexes I-III and/or morphometric estimation of capillarization. Muscle mass was lower in the gastrocnemius muscles of the older animals (2,076 +/- 32 vs. 1,825 +/- 47 mg in young adult vs. late middle-aged, respectively; mean +/- SE) but not the plantaris or soleus muscles. Fibers were smaller in the white region of gastrocnemius muscles but larger in the red region of gastrocnemius muscles of the older animals. There was no difference in the number of capillaries around a fiber, the individual C/F ratio, or the CFPE index between groups for any muscle/region, whereas flux through complexes I-III was reduced by 29-43% in late middle-aged animals. Thus the greater quotient of indexes of anatomic capillarity (individual C/F ratio or CFPE index) and fiber oxidative capacity in soleus and the white region of gastrocnemius muscles, but not in the red region of gastrocnemius muscles of the older animals, shows that anatomic capillarity is maintained in relative excess of oxidative capacity in some muscle regions in late middle-aged rats.

Aging↗

PubMed2004

Skeletal muscle aging in F344BN F1-hybrid rats: I. Mitochondrial dysfunction contributes to the age-associated reduction in VO2max.

Although mitochondrial DNA damage accumulates in aging skeletal muscles, how this relates to the decline in muscle mass-specific skeletal muscle aerobic function is unknown. We used a pump-perfused rat hind-limb model to examine maximal aerobic performance (VO(2max)) in young adult (YA; 8-9-month-old), late middle aged (LMA; 28-30-month-old) and senescent (SEN; 36-month-old) Fischer 344 x Brown Norway F1-hybrid rats at matched rates of convective O(2) delivery (QO(2)). Despite similar muscle QO(2) during a 4-minute contraction bout, muscle mass-specific VO(2max) was reduced in LMA (15%) and SEN (52%) versus YA. In plantaris muscle homogenates, nested polymerase chain reaction revealed an increased frequency of mitochondrial DNA deletions in the older animals. A greater reduction in the flux through electron transport chain complexes I-III than citrate synthase activity in the older animals suggests mitochondrial dysfunction consequent to mitochondrial DNA damage with aging. These results support the hypothesis that a reduced oxidative capacity, due in part to age-related mitochondrial dysfunction, contributes to the decline in aerobic performance in aging skeletal muscles.

Aerobiosis↗

PubMed2004

Skeletal muscle aging in F344BN F1-hybrid rats: II. Improved contractile economy in senescence helps compensate for reduced ATP-generating capacity.

We used a pump-perfused rat hind-limb preparation to compare young adult (YA: 8-9- month-old), late middle-aged (LMA: 28-29-month-old), and senescent (SEN: 36-month-old) rats at similar rates of convective O(2) delivery during a 4-minute contraction bout. We hypothesized that not only would VO(2) and lactate production be reduced, but also that contractile economy would be altered with aging. Peak tension was lower in LMA (42%) and SEN (71%) versus YA. VO(2) and lactate efflux was progressively lower with increasing age. Estimated adenosine triphosphate per N of force was increased in LMA (35%) and reduced in SEN (31%) versus YA. Myosin heavy chain (MHC) analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed a lower MHC type IIb and higher MHC type IIa/IIx in SEN versus YA. Therefore, whereas contractile economy is impaired in LMA, it is improved in SEN, and this latter effect may be due in part to reduced type IIb MHC.

Adenosine Triphosphate↗

PubMed2004

Fiber atrophy and hypertrophy in skeletal muscles of late middle-aged Fischer 344 x Brown Norway F1-hybrid rats.

We examined young adult and late middle-aged male rats to test the hypothesis that gastrocnemius (a locomotor muscle) demonstrates reduced fiber size with aging, whereas soleus (a postural muscle) demonstrates atrophy of some fibers and compensatory hypertrophy in other fibers. Although body mass was greater in late middle-aged animals, mass was reduced in gastrocnemius but not soleus muscle. In another group of animals, physical activity was reduced by 34% in late middle-aged animals. Whereas mean fiber size was lower in gastrocnemius of late middle-aged animals, it was not different in soleus. Histograms revealed atrophied fibers (</=1000 micro m(2)) in soleus and gastrocnemius and hypertrophied fibers (>/=8000 micro m(2)) in soleus with aging. Atrophied fibers often demonstrated no subsarcolemmal mitochondrial staining, suggesting denervation, whereas hypertrophied fibers often demonstrated cytochrome oxidase deficiency, suggesting mitochondrial dysfunction. These results underscore the divergent influences (e.g., physical inactivity, denervation, mitochondrial dysfunction) affecting fiber size with aging.

Aging↗

PubMed2003

Sarcopenia--a critical perspective.

Aging is associated with a progressive decline in skeletal muscle mass and function (sarocopenia). Despite several years of research, controversy exists regarding the manifestations and causes of sarcopenia. In the former respect, whereas a preferential loss of so-called "fast-twitch" muscle fibers occurs in rat models of aging, this appears unlikely in human skeletal muscle. In the latter respect, whereas a decline in physical activity with aging contributes to whole-muscle atrophy, it cannot explain the marked heterogeneity in muscle fiber size seen in aged muscles. Similarly, systemic alterations, such as reduced blood levels of anabolic hormones and nutritional deficits, although involved in modulating the degree of whole-muscle atrophy, cannot explain the observation that only some fibers atrophy and die while most appear unaffected. A further significant question remaining is that if death of some muscle fibers is normal and perhaps advantageous (that is, by removing malfunctioning cells), what is the capacity for muscle fiber regeneration in adult skeletal muscle and can this process be augmented in aging muscles?

Aging↗

PubMed2003

Selected contribution: Bone adaptation with aging and long-term caloric restriction in Fischer 344 x Brown-Norway F1-hybrid rats.

Rodents are commonly used as models for human aging because of their relatively short life span, the ease of obtaining age-specific tissue samples, and lower cost. However, age-associated disease may confound inbred animal studies. For example, numerous physiologically significant lesions, such as chronic nephropathy, are more common in aged Fischer 344 (F344) rats than in other strains (Bronson RT, Genetic Effects of Aging, 1990). Conversely, F344 x Brown-Norway F1-hybrid (F344BN) rats, developed by the National Institute on Aging for aging research, live considerably longer and have fewer pathologies at any given age vs. inbred strains (Lipman RD, Chrisp CE, Hazzard DG, and Bronson RT, J Gerontol A Biol Sci Med Sci 51: 54-59, 1996). To our knowledge, there are no data regarding the effect of age on bone geometry and mechanics in this strain of rat. Furthermore, caloric restriction (CR) extends the mean and maximal life span of animals and significantly reduces age-associated disease but may have adverse consequences for bone growth and mechanics. Thus we investigated the effects of age and CR on bone geometry and mechanics in the axial and appendicular skeleton of F344 Brown-Norway rats. Ad libitum fed rats were assessed at 8 mo (young adult; n = 6), 28 mo (late middle age; n = 5), and 36 mo (senescence; n = 6). CR rats were assessed at 28 mo (n = 6). Tibiae and the sixth lumbar vertebrae (L6) were dissected, scanned (micro-computed tomography) to determine geometry, and tested mechanically. From 8 to 36 mo, there were no significant changes in L6 geometry, and only the cross-sectional moment of inertia changed (increased) with the tibia. CR-induced body mass reductions accounted for changes in L6 load at proportional limit, maximal load, and stiffness (structural properties), but altered tibial structural properties were independent of body mass. In tibiae, geometric changes dominated alterations in structural properties. Those data demonstrated that, whereas aging in ad libitum-fed animals induced minor changes in bone mechanics, axial and appendicular bones were adversely influenced by CR in late-middle-aged animals in different manners.

Adaptation, Physiological↗

PubMed2003

V(O2) max is unaffected by altering the temporal pattern of stimulation frequency in rat hindlimb in situ.

It might be anticipated that fatiguing contractions would impair the aerobic metabolic response in skeletal muscle if significant fatigue developed before full activation of aerobic metabolism. On the basis of this premise, we examined two groups of rats to test the hypothesis that a gradual increase in stimulation frequency would yield a higher maximal O2 uptake (Vo2 max) than beginning immediately with an intense stimulation frequency because of a slower progression of fatigue under the former conditions. In one group of animals, the distal hindlimb muscles were electrically stimulated at a frequency of 60 tetani/min for 4 min (F60; n = 6 rats); in the other group, the muscles were incrementally stimulated for 1 min at each of 7.5, 15, 30, and 60 tetani/min and for 2 min at 90 tetani/min (FInc; n = 5 rats). Despite large differences in rate of fatigue [time to 60% of initial force was 47 +/- 3 (SE) vs. 188 +/- 1 s in F60 and FInc, respectively] and the time at which Vo2 max occurred (120 +/- 15 vs. 264 +/- 6 s), Vo2 max was not different (419 +/- 24 vs. 381 +/- 44 micromol x min-1. 100 g-1). Furthermore, time x tension integral at Vo2 max (3.82 +/- 0.41 vs. 4.07 +/- 0.31 N. s) and peak lactate efflux (910 +/- 45 vs. 800 +/- 98 micromol x min-1. 100 g-1) were not different between groups. Thus our results show that the more rapid progression of fatigue in F60 did not compromise the aerobic metabolic response in electrically stimulated rat hindlimb muscles. However, in both groups, O2 uptake and lactate efflux declined after Vo2 max was attained in similar proportion to a further fall in force, suggesting that ongoing fatigue with intense contractions reduced ATP demand below that requiring maximal aerobic and glycolytic metabolic responses once Vo2 max was reached.

Animals↗

PubMed2003

No effect of trans sodium crocetinate on maximal O(2) conductance or V(O(2),max) in moderate hypoxia.

The lumped parameter describing skeletal muscle diffusional conductance for O(2), DM(O(2)), reflects all of the resistances for O(2) in moving from red cell to muscle fiber mitochondria. The purpose of our study was to determine if the carotenoid compound, trans sodium crocetinate (TSC), which has been reported to increase the diffusivity of O(2) in plasma, improves DM(O(2)) and thus, V(O(2),max) in maximally contracting in situ skeletal muscle. V(O(2),max) was measured in the isolated perfused canine gastrocnemius (n=5) during 3 min of isometric tetanic contractions at 1 Hz, while the animal was breathing 12% O(2) (PA(O(2))=32+/-2 Torr, mean+/-S.E.) under two experimental conditions. The first was a control contraction period and the second (following 60 min recovery) was performed within 5 min after infusion of a 0.1 mg x ml(-1) solution of TSC (total dose 100 microg kg(-1)). There were no significant differences in convective O(2) delivery (11.9+/-2.3 vs. 12.1+/-2.2 ml x min(-1) x 100 g(-1)), V(O(2),max) (9.5+/-1.5 vs. 9.6+/-1.5 ml x min(-1) x 100 g(-1)) or calculated DM(O(2)) (0.37+/-0.03 vs. 0.37+/-0.04 ml x min(-1) x 100 g(-1) x Torr(-1)) between contraction periods. As such, our results show that TSC does not improve performance in maximally contracting canine gastrocnemius muscle in situ under moderately hypoxic conditions, suggesting either that TSC in this situation does not increase plasma O(2) diffusivity or that this step in O(2) diffusion from red cell to myocyte does not constrain DM(O(2)).

Animals↗

PubMed2002

Aerobic power declines with aging in rat skeletal muscles perfused at matched convective O2 delivery.

Although it is well established that maximal O(2) uptake (Vo(2 max)) declines from adulthood to old age, the role played by alterations in skeletal muscle is unclear. Specifically, because during whole body exercise reductions in convective O(2) delivery to the working muscles from adulthood to old age compromise aerobic performance, this obscures the influence of alterations within the skeletal muscles. We sought to overcome this limitation by using an in situ pump-perfused hindlimb preparation to permit matching of muscle convective O(2) delivery in young adult (8 mo; muscle convective O(2) delivery = 569 +/- 42 micromol O(2) x min(-1) x 100 g(-1)) and late middle-aged (28-30 mo; 539 +/- 62 micromol O(2) x min(-1) x 100 g(-1)) Fischer 344 x Brown Norway F1 hybrid rats. The distal hindlimb muscles were electrically stimulated for 4 min (60 tetani/min), and Vo(2 max) was determined. Vo(2 max) normalized to the contracting muscle mass was 22% lower in the 28- to 30-mo-old (344 +/- 17 micromol O(2). min(-1) x 100 g(-1)) than the 8-mo-old (441 +/- 20 micromol O(2) x min(-1) x 100 g(-1); P < 0.05) rats. The flux through the electron transport chain complexes I-III was 45% lower in homogenates prepared from the plantaris muscles of the older animals. Coincident with these alterations, the tension at Vo(2 max) and lactate efflux were reduced in the 28- to 30-mo-old animals, whereas the percent decline in tension was greater in the 28- to 30-mo-old vs. 8-mo-old animals. Collectively, these results demonstrate that alterations within the skeletal muscles, such as a reduced mitochondrial oxidative capacity, contribute to the reduction in Vo(2 max) with aging.

Aerobiosis↗