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Faculties of 1Kinesiology and 2Medicine, University of Calgary, Calgary, Alberta, Canada T2N 1N4
Submitted 9 December 2003 ; accepted in final form 10 February 2004
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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capillary-to-fiber interface; morphometry; mitochondria; sarcopenia
O2 max) is reduced in the skeletal muscles of late middle-aged rats even when provided similar levels of convective O2 delivery (arterial O2 content x blood flow) as young adult muscles, revealing an impairment in the flux of O2 from capillary to cytochrome oxidase in the mitochondria with aging. In that prior study, our laboratory also observed a significant reduction in mitochondrial oxidative capacity in homogenates prepared from the plantaris muscles of the older animals, suggesting that a reduced oxidative capacity is likely one of the factors involved in the reduced capacity of skeletal muscle to use O2 with aging (22). Whether alterations in the anatomic determinants of capillarity might also contribute to the lower O2 max observed in the skeletal muscles of the older animals was not determined in that prior study. In this respect, a recent longitudinal study by McGuire et al. (40) observed a reduced arterial-venous O2 content difference despite similar cardiac output during maximal exercise in humans between the ages of 
20 and 50 yr, suggesting that O2 extraction is reduced at the muscle with aging. Research conducted over the past decade supports the proposal of Honig et al. (27) that the anatomic size of the capillary-to-fiber (C/F) interface (i.e., the region of apposition between capillary and fiber) is an important structural determinant of the capacity for O2 flux from blood to fiber mitochondria. The size of the C/F interface has been shown to vary as a function of muscle fiber mitochondrial volume across a wide range of muscle aerobic capacity (with rare exceptions, e.g., flight muscle; for a review, see Ref. 30). Furthermore, the relationship between the size of the C/F interface and muscle fiber mitochondrial volume is unaltered by increased muscle activity [i.e., exercise training (46) or chronic electrical stimulation (32)] or by chronic exposure to hypoxia (20, 31, 33). Thus the ratio of C/F surface area to fiber mitochondrial volume is conserved across a wide range of conditions, suggesting it is fundamental to matching the structural capacity for O2 supply to the structural capacity for O2 utilization. It is significant that, until very recently, there have been no data regarding how aging might impact this relationship and thus how changes at this level might affect the ability of skeletal muscles to use O2 with aging. Interestingly, this first report suggested that the anatomic size of the C/F interface was maintained in relative excess of fiber mitochondrial volume in senescent soleus (Sol) and extensor digitorum longus muscles (36). Specifically, this study reported an increased C/F surface ratio per fiber mitochondrial volume in Sol and extensor digitorum longus muscles of 35-mo-old vs. 12-mo-old Fischer 344 x Brown Norway F1 hybrid (F344BN) rats.
Because aging is associated with greater reductions in the activity of electron transport chain complexes containing mitochondrial DNA encoded subunits (e.g., complexes I, III, IV, and V) (55) than the activity of mitochondrial enzymes that are entirely nuclear DNA encoded (e.g., complex II, Krebs cycle enzymes) (4, 10, 44), changes in mitochondrial volume may not mirror changes in oxidative capacity in aged muscles. For example, so-called "ragged-red fibers," which exhibit excessive mitochondrial proliferation, often exhibit a lack of cytochrome oxidase activity (44). For this reason, the present study was designed to examine the size of the C/F interface in relation to a measure of muscle oxidative capacity estimated from an enzyme pathway that contains 8 of the 13 polypeptides encoded by the mitochondrial genome (55), the flux through electron transport chain complexes I–III. Furthermore, to address the role of differences in muscle oxidative capacity, we examined muscles/muscle regions representing a wide range of aerobic capacity [Sol muscle and red (GR) and white regions of gastrocnemius (GW) muscle]. We hypothesized that skeletal muscles from late middle-aged rats would exhibit a maintenance of the anatomic size of the C/F interface despite reduced fiber oxidative capacity and that this effect would be similar across muscles exhibiting a wide range of oxidative capacity. This result would suggest that reduced anatomic capillarity does not play a major role in the lower O2 max observed previously (22) in the skeletal muscles of late middle-aged rats.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Surgical procedures. Animals were anesthetized with pentobarbital sodium (65–75 mg/kg ip) and prepared for harvesting of muscles for morphometric and/or biochemical analyses. The skin was removed from the right hindlimb, the iliac artery and vein were then ligated (to prevent excessive bleeding), and the gastrocnemius, plantaris, and Sol muscles were excised, dissected free of fat and connective tissue, and weighed. After the muscles were removed, animals were prepared for in situ pump perfusion of the left hindlimb [data part of a previously published study (22)] and/or euthanized with an intracardiac injection of 25 mg of pentobarbital. A cross section through the midbelly of the right Sol and gastrocnemius muscles was mounted transversely in embedding medium (Shandon Cryomatrix) on cork, and frozen in liquid isopentane cooled in liquid nitrogen for subsequent morphometric analyses (see below). The entire plantaris, remaining portion of the Sol (50–80 mg), and portions from the GW and GR muscles (50–80 mg) were frozen in liquid nitrogen for biochemistry (see Biochemistry). The Sol muscle and the GW and GR muscle were selected to represent slow oxidative, fast glycolytic, and fast oxidative muscle, respectively, whereas the plantaris muscle was selected as representative of the rat distal hindlimb as a whole (2). Samples were stored at -70°C until sectioned for morphometry or homogenized for biochemistry.
Biochemistry. With the use of methods described previously (21, 22), frozen muscles were thawed on ice and homogenized at 4°C in phosphate buffer (pH 8.0) containing 0.05 M Tris·HCl and 0.67 M sucrose before being stored at -70°C until assayed. On the day of analysis, homogenates were thawed on ice, and the rate of reduction of cytochrome c at 38°C was followed spectrophotometrically at 550 nm (Biochrom Ultrospec 2100 Pro) after the addition of 20 µl of homogenate to the reaction media (containing 20 µl of 1.0 M phosphate buffer, pH 8.0, 20 µl of 0.1 M NaN3, 60 µl of 1% cytochrome c, and 25 µl of 0.01 M NADH, bringing the total volume to 1 ml with double-distilled H2O). Samples were measured in triplicate, with the average activity over the linear portion of the absorbance vs. time relationship used to represent the activity of the complex I–III pathway. The units (µmol·min-1·g protein-1) represent the rate of appearance of reduced cytochrome c. Due to some decline in activity of this pathway with repeated freeze-thaw cycles, all samples were processed after one or two freeze-thaw cycle(s). Protein content in each muscle sample was determined by the biuret method, such that specific activity of the complex I–III pathway could be expressed relative to total muscle protein.
Morphometry. Ten-micrometer-thick sections from Sol and gastrocnemius muscles in six animals from each group were cut on a cryostat after equilibrating the samples to the temperature of the cryostat (-21°C). Capillaries were identified in lead-ATPase-stained sections (50), as described previously (25). Our laboratory previously determined that the number of capillaries revealed by this histochemical method is not different from that seen with vascular perfusionfixation (25). A single observer, who was naive to the identity of the samples, performed all morphometry. Images were captured from the microscope stage (Nikon Eclipse E400) by a digital camera (Nikon CoolPix 990) and downloaded to a computer for image analysis (Sigmascan Pro 5.0, SPSS Science). The sampling strategy employed for image capture involved randomly selecting two to three fields from the entire Sol muscle cross section or GW or GR muscle (26). For each image collected, a sampling frame was created within the image, such that all fibers intersecting the edges of the sampling frame were contained completely within the image. This approach is the same as that used with histochemically stained muscle previously (25) and, by allowing the complete area of all fibers wholly or partially contained within the sampling frame to be measured, prevents bias of the data toward smaller fibers that would otherwise occur due to the fact that smaller fibers have a greater probability than larger fibers of being completely contained within the image (R. T. Hepple and O. Mathieu-Costello, unpublished observations). Fiber cross-sectional area and perimeter, the number of capillaries around a fiber, and the individual C/F ratio (24) were measured at 200x in each muscle (Sol; an average of 40 ± 2 fibers analyzed per sample; mean ± SE) or muscle region (GW and GR; an average of 45 ± 1 and 42 ± 2 fibers analyzed per sample, respectively). Capillary density was estimated using the fiber as the reference space (11). The size of the C/F interface was estimated as the quotient of the individual C/F ratio and fiber perimeter for each fiber (CFPE index) (19, 25). Fiber oxidative capacity in each muscle or muscle region was estimated by taking the product of mean fiber cross-sectional area and the flux through electron transport chain complexes measured in homogenates for each muscle (see Biochemistry above).
Statistical analysis. Values are reported means ± SE. Differences between groups were assessed by two-way ANOVA (muscle or muscle region x age) with a Bonferroni post hoc test. The 
was set at 0.05.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Mitochondrial oxidative capacity. Similar to our laboratory's previous findings (22), the flux through electron transport chain complexes I–III was 43% lower in the plantaris muscle of the older animals, with values of 56 ± 4 vs. 32 ± 2 µmol·min-1·g protein-1 for young adult (n = 8) vs. older rats (n = 9), respectively. The present findings demonstrate that similar reductions are also apparent in other regions of the distal hindlimb muscles of older animals. As shown in Fig. 1, the complex I–III activity was significantly reduced in Sol muscle (35 ± 4 vs. 21 ± 3 µmol·min-1·g protein-1 for young adult vs. older rats, respectively) and GR (74 ± 10 vs. 47 ± 6 µmol·min-1·g protein-1) but not in GW muscle (20 ± 3 vs. 14 ± 3 µmol·min-1·g protein-1; P = 0.46) of the older animals.
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Muscle morphometry. Note that due to the extensive appearance of adjoining capillaries around the fibers in cross sections of Sol muscle of one young adult and one late middle-aged animal (such that a single capillary appeared to almost completely encircle some fibers), it was not possible to evaluate capillarity by our methods for these samples. Thus values are based on five animals in each group for the Sol muscle. In addition, data for GW muscle in the late middle-aged group are based on five animals because there was insufficient tissue to complete biochemical analysis (complex I–III activity) for this sample.
As noted previously in our laboratory's study examining changes in fiber-size distribution in the same muscle samples (26), fiber cross-sectional area was lower in GW, whereas it was greater in GR in the 28- to 30-mo-old animals compared with the 8-mo-old animals (Table 3; Fig. 2). Similarly, fiber perimeter was lower in GW, whereas it was greater in GR muscle. Neither fiber cross-sectional area nor perimeter was different in the Sol muscle between age groups. Note that the fiber cross-sectional area obtained in the Sol muscle via random sampling of 40 fibers/sample (present results) is similar to that obtained previously in the same muscle cross sections (26) by systematic sampling across the entire muscle cross section to yield measurements of 170 fibers/sample. The number of capillaries around a fiber and individual C/F ratio were not different in any muscle or muscle region between age groups (Fig. 2; Table 3). However, due to the differences in fiber cross-sectional area, capillary density was greater in GW and lower in GR muscle of the 28- to 30-mo-old vs. the 8-mo-old animals. In contrast, the estimate of the size of the C/F interface, obtained by taking the quotient of the individual C/F ratio and fiber perimeter (CFPE index; Fig. 3), was not different between groups. Estimation of fiber oxidative capacity in each muscle or muscle region, by taking the product of fiber cross-sectional area and flux through electron transport chain complexes I–III in muscle homogenates for each muscle or muscle region, revealed a main effect for a lower fiber oxidative capacity in the older animals; post hoc analysis showed this was only significant in Sol muscle (Table 3). There was a main effect for a greater quotient of the individual C/F ratio and fiber oxidative capacity in the late middle-aged animals; post hoc analysis showed this was significant in GW and in Sol muscles (Fig. 4). Similarly, examination of the quotient of the CFPE index and fiber oxidative capacity revealed a main effect for a greater size of the C/F interface relative to fiber oxidative capacity in the late middle-aged animals; post hoc analysis showed this was significant in GW and in Sol muscles (Fig. 4).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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O2 max was lower in late middle-aged vs. young adult skeletal muscles perfused at similar rates of convective O2 delivery (22), revealing an impairment at one or more points in the pathway of O2 flux from blood to cytochrome oxidase in the mitochondria. The purpose of the present investigation was to assess whether a reduced anatomic size of the C/F interface plays a role in this response. Morphometric analyses in muscle cross sections revealed that an estimate of the size of the C/F interface, CFPE index (19, 25), was unchanged in Sol muscles or in GW or GR muscles of late middle-aged animals vs. young adults. In the Sol muscles, this was due to preserved fiber size and an unchanged number of capillaries around a fiber and individual C/F ratio with aging. In GW, this was due to a modest reduction in mean fiber size and no change in capillary number around a fiber or individual C/F ratio in the older animals. In GR, this was due to a modest increase in fiber size and a tendency (not significant) to increase capillary number around a fiber and individual C/F ratio in the older animals. In contrast to the maintained fiber capillarity, the flux through electron transport chain complexes I–III in muscle homogenates was reduced by 40% in Sol muscles and by 36% in GR in late middle-aged vs. young adult F344BN rats. Use of these values to compute a fiber oxidative capacity (i.e., the product of fiber cross-sectional area and the flux through electron transport chain complexes I–III) showed that fiber oxidative capacity was reduced in Sol muscles (due to a reduced muscle oxidative capacity and unchanged fiber size) but unchanged in GR (increased fiber size offsetting a reduced muscle oxidative capacity) and GW (modestly reduced fiber size and unchanged muscle oxidative capacity) of the late middle-aged animals. Thus taking the quotient of the individual C/F ratio and fiber oxidative capacity revealed a greater anatomic capillarity relative to fiber oxidative capacity in GW and Sol muscle of the late middle-aged animals, whereas it was unchanged in GR. The same conclusion was reached when the quotient of the CFPE index and fiber oxidative capacity was examined. As such, these results suggest that a reduced anatomic size of the C/F interface does not play a major role in the reduced ability of aged muscles to use O2 during high-intensity contractions. The distal hindlimb muscles of the rat exhibit a wide distribution of fiber types, with distinct regions dominated by a particular metabolic character (2). To be specific, the Sol is a postural muscle that is comprised of a high proprtion of type I fibers. The gastrocnemius muscle exhibits marked regionalization, with a superficial region exhibiting a high proportion of type IIb fibers (GW) and a deep highly oxidative red portion (GR) comprised largely of type IIa and type I fibers (2). In addition to fiber-type differences, these muscles and muscle regions exhibit differences in oxidative capacity and capillarization. Similar to the present results for the flux through electron transport chain complexes I–III in young adult rats, GW exhibits the lowest oxidative capacity, the Sol muscle is intermediate, and GR exhibits the highest oxidative capacity (9). Similarly, the C/F ratio is lowest in GW but very similar in the Sol muscle and GR (16, 17), as seen in the young adult rats of the present investigation. It is for these reasons that these muscles lend themselves well to investigations aimed at understanding the role of fiber type and/or oxidative capacity in adapting to a variety of conditions (e.g., exercise training, disease), including aging.
Assessing the structural resistance to O2 flux from C/F mitochondria. The present results showed that neither the number of capillaries around a fiber nor the individual C/F ratio was different in skeletal muscles of late middle-aged animals compared with young adult animals. Due to opposing changes in fiber size, capillary density was increased in GW (fiber size reduced) but reduced in GR (fiber size increased) of late middle-aged animals. The potential causes of these differential effects of aging on fiber size, as well as the increased heterogeneity in fiber size seen in these muscles, have been discussed previously (26). The maintained fiber size in the Sol muscle of the late middle-aged animals is likely due to the influence of increased body mass on this postural muscle with aging (increased body mass counteracting the effect of reduced physical activity), and the increased fiber size in GR may, likewise, be in compensation for the increased body mass if this region is recruited to assist the Sol during postural stance. On the other hand, the reduced fiber size in GW of the older animals is likely due to lower physical activity (26). In contrast to the minimal changes in anatomic capillarity, muscle oxidative capacity (flux through electron transport chain complexes I–III) was reduced in plantaris and Sol muscles and in GR of the late middle-aged animals. This is similar to data in sedentary humans and animal models showing reduced mitochondrial enzyme activities in aged skeletal muscles (6, 12, 41, 52). In regard to the minimal changes in capillarization observed in the late middle-aged animals, changes in skeletal muscle capillary number with aging are equivocal. Some studies report no change (1, 5, 28), others report a reduction (6, 8, 14, 18), and others have even reported an increase (7, 45) in C/F ratio and/or capillary density with aging. However, prior studies have not examined capillarity from the perspective of where present evidence suggests the greatest structural resistance to O2 flux resides.
Since the pioneering work of August Krogh (29), who suggested that diffusion distance from capillaries to the most distant myocyte mitochondria determined O2 flux in this region, studies have attempted to refine the location of "bottlenecks" in the diffusion of O2 in muscles. Myoglobin spectroscopy measurements in animal models (15) and exercising humans (43, 48) show a large drop in PO2 between capillary blood and myocyte interior, revealing a large resistance to O2 flux in the area of apposition between capillary and myocyte sarcolemma (27), a region known as the C/F interface (38). A number of morphometric measures have been developed to quantify the size of the C/F interface. Mathieu-Costello et al. (34) introduced the C/F perimeter ratio, which is estimated by intersection counting in vascular perfusion-fixed muscles. This method is unique in that it accounts for intersample differences in capillary geometry (i.e., capillary length contributed by tortuosity and branching) and, as a result, has been shown to vary little with changes in sarcomere length (34) and permits comparison of muscles that have different capillary geometry (e.g., avian or mammalian flight muscle vs. mammalian limb muscle; for a review, see Ref. 35). We used the C/F perimeter ratio as the theoretical basis for developing a method to estimate the size of the C/F interface in biopsy material processed for histochemistry (19). This measurement (CFPE index) is calculated as the quotient of the individual C/F ratio and fiber perimeter for individual fibers. Note that the difference between the CFPE index and the C/F perimeter ratio is that the CFPE index does not measure capillary diameter (19, 25) and, as such, unlike the C/F perimeter ratio, the CFPE index cannot take into account differences in capillary geometry, and it can be biased by intersample variability in sarcomere length (25). It is thus an approximation of the size of the C/F interface.
Notwithstanding these issues, the CFPE index is closely related to the C/F perimeter ratio when measured in the same samples (25). Furthermore, because sarcomere length in frozen biopsy samples exhibits a relatively small variability (coefficient of variation = 7%; calculated from Ref. 25), estimates of the size of the C/F interface using the CFPE index permit useful comparisons, provided the muscle samples are from the same species and/or muscle group (25). However, our estimate of the size of the C/F interface could be biased if aging caused a change in capillary geometry or capillary diameter (see preceding paragraph for explanation). In this respect, a recent study (51) examining capillary structure and erythrocyte hemodynamics in spinotrapezius muscles showed no difference in the degree of capillary tortuosity or capillary diameter when examined at similar sarcomere lengths in 26- to 28-mo-old vs. 6- to 8-mo-old F344BN rats. As such, the lack of difference in CFPE index between the distal hindlimb muscles of young adult and late middle-aged F344BN rats suggests that the anatomic size of the C/F interface, and thus the structural resistance to O2 flux, is not impaired in muscles from older animals. Note that the CFPE index plotted as a function of fiber cross-sectional area was similar in both age groups in each of the muscles or muscle regions examined (R. T. Hepple, unpublished observations), suggesting that the previously documented heterogeneity in fiber size in these late middle-aged muscles (26) does not obscure the comparisons between age groups. It should also be noted that to permit us to examine an enzymatic estimate of fiber oxidative capacity required the use of frozen-fixed tissue, and, because capillary diameter cannot be readily measured in histochemically stained muscles, the CFPE index was the measure of choice to estimate the anatomic size of the C/F interface in our study.
Our results are similar in some respects to a recent report in skeletal muscles of 12-, 24-, and 35-mo-old F344BN rats (36) that employed the more rigorous stereological approach to quantify the anatomic size of the C/F interface. Specifically, Mathieu-Costello et al. (36) reported that C/F surface ratio [the product of C/F perimeter ratio and the capillary anisotropy coefficient c'(K',0); Ref. 34] was higher in the extensor digitorum longus and unchanged in Sol muscle of 35-mo-old (senescent) vs. 12-mo-old (adult) F344BN rats. Fiber mitochondrial volume (i.e., the product of mitochondrial volume density and mean fiber cross-sectional area) was reduced in proportion to the degree of fiber atrophy in both muscles. Thus, similar to our observations in Sol and GW in 28- to 30-mo-old (late middle aged) vs. 8-mo-old (young adult) F344BN rats, Mathieu-Costello et al. observed that the size of the C/F interface was maintained in relative excess of fiber mitochondrial volume with aging. Whereas our results show maintained fiber size in Sol muscles of the older animals, Mathieu-Costello et al. observed a marked reduction of fiber size in Sol muscles of the senescent animals. Because we also see a marked reduction in mean fiber cross-sectional area in Sol muscles of 36-mo-old F344BN rats (J. Heth and R. T. Hepple, unpublished observations), this difference between studies is most likely due to the advanced age of the rats examined by Mathieu-Costello et al. (35 mo old) vs. our present study (28–30 mo old).
Whereas our findings show that anatomic capillarity is well maintained in muscles from late middle-aged animals, our results do not address alterations in the distribution of erythrocytes in the microvasculature. Theoretical calculations (13) suggest that the majority of O2 flux occurs in the regions of close apposition between erythrocytes and the capillary wall, rather than the intererythrocyte space (i.e., plasma). Thus it is possible that, despite maintained anatomic capillarity, the functional distribution of the erythrocytes may be altered such that the instantaneous surface area between erythrocyte and capillary wall is reduced in aged muscles. However, Russell et al. (51) observed no difference in capillary tube hematocrit in spinotrapezius muscle at rest of 26- to 28-mo-old vs. 6- to 8-mo-old F344BN rats, suggesting no change in the instantaneous surface area available for O2 diffusion within individual capillaries with aging. On the other hand, there was a reduced lineal density of capillaries (those with and without flowing erythrocytes) and an increased mean erythrocyte velocity and flux under these resting conditions (51). Although we found no changes in anatomic capillary density, if an elevated erythyrocyte velocity occurs under contracting conditions, this could compromise O2 diffusion by reducing the capillary transit time.
Functional significance of relationship between capillarization and oxidative capacity. It is not clear why capillarization would be maintained in relative excess of fiber oxidative capacity in some muscle regions with aging. There is abundant structural evidence that the anatomic size of the C/F interface is maintained in proportion to fiber mitochondrial volume across muscles exhibiting a wide range of oxidative capacity. Similarly, adaptation in skeletal muscle, for example in response to increases in muscle activation or in response to chronic exposure to hypoxia, does not affect the relationship between the size of the C/F interface and fiber mitochondrial volume (for a review, see Ref. 35). As such, it would appear that this relationship is a fundamental property of muscles that reflects a matching of the structural capacity for O2 supply with the structural capacity for O2 utilization. On the other hand, the consequence of altering this relationship for skeletal muscle performance is less certain. For example, although treatment of rats with the 5'-AMP-activated protein kinase activator 5-aminoimadazole-4-carboximide-1-
-D-ribofuranoside leads to increased oxidative enzyme activities without affecting capillary number or fiber size (53), and thus would cause a reduction in the ratio of size of the C/F interface and fiber oxidative capacity, the functional consequences of this were not examined. Based on data from our laboratory (21) and that of Terjung and colleagues (39, 49) showing that acute reduction of oxidative capacity yields a proportional reduction in O2 max (passing through the origin), possessing a greater size of the C/F interface relative to fiber oxidative capacity (as would occur under these latter experimental conditions) affords little protection to O2 uptake. Whether this applies to aging skeletal muscles, where other changes [e.g., altered myoglobin concentration (3)] may accompany a reduced oxidative capacity, is unknown. Altered regulation of angiogenesis could explain the maintenance of capillarization in relative excess of fiber oxidative capacity in some muscles with aging. Because the results are similar regardless of whether one considers a structural estimate of fiber oxidative capacity [i.e., fiber mitochondrial volume, see Mathieu-Costello et al. (36) or an enzymatic estimate of fiber oxidative capacity (as used here)], this effect appears to be independent of age-associated mitochondrial dysfunction, although the fact that capillarization and fiber oxidative capacity were proportionally maintained with aging in the most oxidative muscle region studied (GR) suggests that muscles with a lower oxidative capacity are more likely to be affected. Further research is required to clarify the physiological basis of these results.
In summary, our results show relatively modest changes in capillarization in distal hindlimb skeletal muscles from late middle-aged F344BN rats. The number of capillaries around a fiber and individual C/F ratio were well maintained in older animals. Although capillary density was reduced in GR, it was increased in GW and unchanged in Sol of the older animals. On the other hand, there were no differences in an estimate of the size of the C/F interface (CFPE index) between age groups, suggesting a preserved structural capacity for O2 flux up to late middle age. Interestingly, there was a greater quotient of indexes of anatomic capillarity (individual C/F ratio or CFPE index) and fiber oxidative capacity in late middle-aged rats in Sol muscles and GW, whereas it was unchanged in the highly oxidative GR. We conclude that alterations in the anatomic size of the C/F interface do not play a major role in the fall in skeletal muscle aerobic performance with aging.
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ACKNOWLEDGMENTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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GRANTS
This work was supported by an operating grant from Canadian Institutes of Health Research (CIHR) (MOP 57808) and a CIHR Institute of Aging New Investigator Award (to R. T. Hepple).
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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O2 kinetics in old and young individuals. J Appl Physiol 82: 63-69, 1997.O2. Am J Physiol Heart Circ Physiol 251: H789-H799, 1986.O2 peak and the capillary supply to skeletal muscle. J Appl Physiol 82: 1305-1310, 1997.This article has been cited by other articles:
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B. J. Behnke, M. D. Delp, D. C. Poole, and T. I. Musch Aging potentiates the effect of congestive heart failure on muscle microvascular oxygenation J Appl Physiol, November 1, 2007; 103(5): 1757 - 1763. [Abstract] [Full Text] [PDF]
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E. L. Rezende, T. Garland Jr, M. A. Chappell, J. L. Malisch, and F. R. Gomes Maximum aerobic performance in lines of Mus selected for high wheel-running activity: effects of selection, oxygen availability and the mini-muscle phenotype J. Exp. Biol., January 1, 2006; 209(1): 115 - 127. [Abstract] [Full Text] [PDF]
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A. N. Croley, K. A. Zwetsloot, L. M. Westerkamp, N. A. Ryan, A. M. Pendergast, R. C. Hickner, W. E. Pofahl, and T. P. Gavin Lower capillarization, VEGF protein, and VEGF mRNA response to acute exercise in the vastus lateralis muscle of aged vs. young women J Appl Physiol, November 1, 2005; 99(5): 1872 - 1879. [Abstract] [Full Text] [PDF]
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O. Mathieu-Costello, Y. Ju, M. Trejo-Morales, and L. Cui Greater capillary-fiber interface per fiber mitochondrial volume in skeletal muscles of old rats J Appl Physiol, July 1, 2005; 99(1): 281 - 289. [Abstract] [Full Text] [PDF]
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 H. B Rossiter, R. A Howlett, H. H Holcombe, P. L Entin, H. E Wagner, and P. D Wagner Age is no barrier to muscle structural, biochemical and angiogenic adaptations to training up to 24 months in female rats J. Physiol., June 15, 2005; 565(3): 993 - 1005. [Abstract] [Full Text] [PDF]
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T. P. Gavin, H. W. Stallings III, K. A. Zwetsloot, L. M. Westerkamp, N. A. Ryan, R. A. Moore, W. E. Pofahl, and R. C. Hickner Lower capillary density but no difference in VEGF expression in obese vs. lean young skeletal muscle in humans J Appl Physiol, January 1, 2005; 98(1): 315 - 321. [Abstract] [Full Text] [PDF]
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 J. L. Hagen, D. J. Krause, D. J. Baker, M. H. Fu, M. A. Tarnopolsky, and R. T. Hepple Skeletal Muscle Aging in F344BN F1-Hybrid Rats: I. Mitochondrial Dysfunction Contributes to the Age-Associated Reduction in VO2max J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2004; 59(11): 1099 - 1110. [Abstract] [Full Text] [PDF]
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R. T. Hepple, J. L. Hagen, D. J. Krause, and D. J. Baker Skeletal Muscle Aging in F344BN F1-Hybrid Rats: II. Improved Contractile Economy in Senescence Helps Compensate for Reduced ATP-Generating Capacity J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2004; 59(11): 1111 - 1119. [Abstract] [Full Text] [PDF]
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