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Department of Integrative Biology, University of Texas Medical School, Houston, Texas 77030
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Marsh, Daniel R., David S. Criswell, James A. Carson, and
Frank W. Booth. Myogenic regulatory factors during regeneration of
skeletal muscle in young, adult, and old rats. J. Appl. Physiol. 83(4): 1270-1275, 1997.
Myogenic
factor mRNA expression was examined during muscle regeneration after
bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the
tibialis anterior muscle in the young rats had recovered to control
values by 21 days postbupivacaine injection but in adult and old rats
remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was
significantly increased in muscles of young, adult, and old rats 5 days
after bupivacaine injection. Subsequently, myogenin mRNA levels in
young rat muscle decreased to postinjection control values by
day 21 but did not return to control
values in 28-day regenerating muscles of adult and old rats. The
expression of MyoD mRNA was also increased in muscles at
day 5 of regeneration in young, adult,
and old rats, decreased to control levels by day
14 in young and adult rats, and remained elevated in
the old rats for 28 days. In summary, either a diminished ability to
downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in
old rat muscles, or the continuing myogenic effort includes elevated
expression of these mRNAs.
aging; bupivacaine injection; muscle mass; recovery
INTRODUCTION IN EXPERIMENTAL MODELS of muscle injury, the nature of
the muscle damage dictates the extent to which revascularization,
phagocytosis, reinnervation, and myogenesis must occur to regenerate
the muscle (34). With the exception of phagocytosis of muscle fiber
debris, the cellular and molecular events that occur after
intramuscular injection of bupivacaine are similar to what must occur
during embryonic myogenesis. Bupivacaine injection causes a dissolution of the sarcolemma that leads to rapid muscle fiber necrosis but does
not affect basal lamina, satellite cells, intramuscular nerves, and
blood vessels (16). The subsequent recapitulation of myogenesis can be
used to examine the regenerative capacity of skeletal muscle in young,
adult, and old rats.
The extrinsic exposure of skeletal muscle to growth factors is altered
during the lifetime of an animal. This change could affect its ability
to regenerate during aging (4). For example, in the embryo and in the
young rat, hormones and growth factors favor muscle growth (reviewed in
Refs. 12 and 14); in the adult, many of these endocrine and growth
factors are downregulated (17) because only maintenance of mature
muscle cells is required. Skeletal muscle atrophy with senescence is
evidence of an alteration in the extracellular and/or
intracellular milieu that has diminished the capacity of the muscle to
maintain expression of neuromuscular proteins. This may be because of
an intrinsic program, but significant modifications of extrinsic
factors acting on the muscle, such as voluntary activity patterns,
thyroid hormone levels, growth hormone levels, and axoplasmic
transport, cannot be discounted.
In young rats injected with bupivacaine, satellite cells proliferate,
differentiate, and fuse to form myotubes so that recovery of muscle
mass and force is complete within 21 days (29, 30). Differentiation of
myogenic cells, during embryogenesis and in muscle culture experiments,
has been shown to be regulated by genes, the protein products of which
have basic helix-loop-helix sequences that bind to DNA. This family of
myogenic factors, which includes MyoD, myogenin, Myf-5, and MRF4
(myf-6, herculin), forms dimers with ubiquitous proteins such as E12 or
E47, resulting in heterodimeric complexes that bind to the E-box
consensus DNA sequence (5 Impaired regeneration of skeletal muscle in old animals has been
reported after ischemic necrosis (33), bupivacaine injection (4, 32),
and transplantation of muscle grafts (3). A deficiency in reinnervation
has been proposed to account for the poor regeneration of autografted
muscle observed in aged rats (4). Bupivacaine injection into muscles of
young, adult, and aged rats tests the ability of the muscle to
reactivate myogenic processes, regenerate muscle fibers, and synthesize
muscle proteins. An incomplete recovery of muscle protein in muscle of
old rats (22) suggests that, in addition to a possible deficiency in
reinnervation, myogenesis is also impaired with aging. A prolonged
expression of insulin-like growth factor I (IGF-I) mRNA has been
observed in regenerating muscles of adult and old rats compared with
that of young rats (22). IGF-I induces myogenin mRNA expression in
differentiating muscle cells (11); therefore, elevated expression of
myogenic factor mRNAs may also persist in muscles of adult and old rats during regeneration. The myogenin gene has been shown to be involved in
the control of muscle cell differentiation (8) and regulation of
muscle-specific gene expression (1). Thus it is possible that defective
regulation of myogenin mRNA in regenerating muscles of old rats might
be associated with impaired regeneration.
The purpose of the present study was to examine the effect of aging on
myogenic factor mRNA expression during muscle regeneration. Muscle
regeneration was examined in Fischer 344/Brown Norway F1 hybrid male
rats of appropriate ages to obtain muscle in the growth phase (3 mo
old), maintenance phase (18 mo old), and atrophic phase (31 mo old). We
hypothesized that MyoD, myogenin, and MRF4 mRNA expression would be
elevated in regenerating muscles but that the increase would be less in
regenerating muscles of old rats compared with that in young rats,
relative to contralateral controls. Furthermore, we hypothesized that,
like IGF-I mRNA expression, the increased expression of myogenic factor
mRNAs would be prolonged in regenerating muscles of adult and old rats
compared with young rats. We expected myogenic factor mRNA expression,
in regenerating muscles of young rats, to return to control levels
within 15 days, which coincides with the period of rapid muscle protein
accretion. The present study is a part of our long-term purpose: to use
this model of muscle regeneration to gain more insight into the
mechanism of muscle atrophy that occurs with aging.
MATERIALS AND METHODS
-CANNTG-3) that is found in the
regulatory region of many muscle-specific genes (24). Increased
expression of the above-mentioned myogenic factor genes has been
demonstrated in denervated muscles (2, 9), in hindlimb muscle of aged mice (25), and in regenerating skeletal muscle of young rats 2-3
mo of age (13, 15, 28). MRF4 mRNA has recently been shown to decrease
in the soleus muscle of immobilized limbs, whereas the level of
myogenin mRNA was unaltered (21). Therefore, conditions in which muscle
atrophy is prevalent (denervation, aging, limb immobilization) are not
always associated with increased expression of myogenic factor mRNAs.
80°C until further analysis.
Rats were euthanized by cervical dislocation while under anesthesia.
Total RNA isolation.
Entire tibialis anterior muscles were powdered under liquid nitrogen
with a mortar and pestle. Total RNA was extracted from an aliquot of
150-300 mg of powdered muscle by using the guanidine thiocyanate
method of Chomczynski and Sacchi (6) with Trisolve (Biotecx
Laboratories). The extracted RNA was dissolved in
diethylpyrocarbonate-treated water and quantified
spectrophotometrically at 260-nm wavelength. The integrity and
concentration of the RNA were confirmed by visual inspection of
ethidium bromide-stained 18S and 28S ribosomal (r)RNAs before use of
the total RNA for Northern blots.
mRNA determination.
Northern blot analysis was used to assess the relative abundance of
myogenin, MyoD, MRF4, and 18S mRNAs in contralateral control and
bupivacaine-injected muscles and in control tibialis anterior muscles.
Extracted RNA (15 µg) for each muscle was loaded onto a denaturing
1% agarose gel [1 × 3-(N-morpholino)propanesulfonic acid
and 6.7% formaldehyde] and electrophoresed at 4 V/cm for 3 h.
The RNA was then transferred to a nylon membrane
(Hybond-N+, Amersham) by capillary
action and ultraviolet cross-linked to the membrane when transfer was
complete. A rat myogenin cDNA probe was prepared by random priming the
full-length cDNA cut from Bluescript plasmid (37). Similarly, probes
for the full-length cDNAs for MyoD and MRF4 were prepared from EMSV
plasmids generously provided by Eric Olson.
The RNA-containing membrane was prehybridized with 12 ml hybridization
buffer (QuickHyb, Stratagene) for 40 min at 68°C. One of the
myogenin, MyoD, or MRF4 probes [>3 × 107 counts/min (cpm); sp. act.
>1 × 109 cpm/µg
DNA] was mixed with the hybridization buffer and incubated for 2 h at 68°C. The membrane was washed two times with 2× sodium chloride-sodium citrate (SSC) with 0.1% sodium dodecyl sulfate (SDS;
22°C, 15 min) and once with 0.1× SSC with 0.1% SDS
(55°C, 30 min) (5). The membrane was then visualized
autoradiographically after an exposure time of 1 h (18S), 48 h (MRF4),
or 65 h (MyoD, myogenin) with one intensifying screen at
80°C, and the bands corresponding to 18S, myogenin, MyoD,
and MRF4 mRNAs were quantified by densitometry scanning (BioImage,
Millipore) as integrated optical density (IOD). The IOD values of 18S
mRNA were used to correct loading efficiencies for myogenin, MyoD, and
MRF4 mRNA's IOD. Data are expressed per milligram muscle
by multiplying total muscle RNA concentration (µg/mg), as determined
by Fleck and Munro (23a), by IOD for a mRNA/µg RNA loaded into gel.
Statistics.
An analysis of variance was used to determine whether significant
differences occurred at the P 
0.05 level for body weights, muscle mass, and myogenin, MyoD,
and MRF4 mRNAs among control young, adult, and old rat
muscles that received no bupivacaine injections. A multifactorial
analysis of variance (age, bupivacaine treatment, and recovery day) was
used to determine whether significant differences occurred at
the P 0.05 level for muscle mass
and mRNAs for myogenin, MyoD, and MRF4 among young, adult, and old tibialis anterior muscles after bupivacaine injection. When significant interaction of main effects occurred, Newman-Keuls post hoc tests were
used to assess significance at P 0.05.
RESULTS
), adult (18 mo of age; 
), and old
(31 mo of age; 
) Fischer 344/Brown Norway F1 rats after damage
produced by an intramuscular injection of bupivacaine. Values are means ± SE; n = 15 rats/age group, 5 rats/day. Data are presented as a percentage of contralateral control
muscle. Absolute values for each control are presented in
RESULTS. Contralateral control values
for each point of recovery in each age group have been averaged, and
mean ± SE is shown as day 0 of
recovery. * Significantly different from adult and old rats,
P < 0.05.
Myogenin, MyoD, and MRF4 mRNAs. Myogenin, MyoD, and MRF4 mRNA expression was similar between the uninjected tibialis anterior muscles (control) of young and adult rats. In contrast, expression of myogenin, MyoD, and MRF4 mRNAs was greater in the control muscle of old rats compared with that of adult and young rats (Figs. 2, 3, 4). The greatest relative increase occurred for myogenin mRNA, which was 1,090% greater in old control muscle, whereas MyoD and MRF4 mRNAs were increased by 187 and 66%, respectively, relative to young control muscle.
During muscle regeneration, expression of myogenin, MyoD, and MRF4 mRNAs was altered in young, adult, and old rat muscles recovering from bupivacaine injection. In young rats, myogenin mRNA expression was dramatically increased (18-fold relative to control) at 5 days of recovery, attenuated by 14 days (2.7 fold), and then returned to its respective control levels by 21 days (Fig. 2). The temporal expression of myogenin mRNA in regenerating muscles of adult and old rats differed from that of young rats. In adult rat muscle, myogenin mRNA expression was dramatically increased (13-fold relative to control) at 5 and 14 days of regeneration. At 28 days postbupivacaine injection, myogenin mRNA levels in adult rat muscle remained fourfold greater than its age-group control (Fig. 2). In contrast to young (18-fold) and adult (13-fold) rat muscle, myogenin mRNA expression in old rat muscle was only increased 2.5-fold at 5 days and remained elevated 1.6- to 2-fold above its age-group control at 14 and 21 days postbupivacaine injection. Myogenin mRNA levels in old regenerating muscle was not different from its respective control by 28 days of recovery (Fig. 2). MyoD mRNA expression in regenerating muscles of young rats was significantly elevated (3-fold) relative to control muscle at 5 days postbupivacaine injection (Fig. 3). At all subsequent time points in young rats, MyoD mRNA levels were similar to their age-matched control muscle. The temporal expression of MyoD mRNA in regenerating muscles of adult rats was similar to that of young rats. In contrast, MyoD mRNA expression in regenerating muscles of old rats was elevated two- to threefold above its age-group control at 5, 14, 21, and 28 days postbupivacaine injection (Fig. 3). The temporal expression of MRF4 mRNA during regeneration differed from that of myogenin and MyoD. In regenerating muscles of young rats, MRF4 mRNA levels were significantly decreased by 46% at day 5 when the expression of myogenin and MyoD mRNAs was maximal, significantly increased by 239% at day 14, coincident with decreased expression of myogenin and MyoD mRNAs, presumably once myotubes have been formed, and similar to control values by day 21 of recovery (Fig. 4). In contrast to expression of myogenin and MyoD mRNAs, there was no difference in the temporal pattern of MRF4 mRNA expression among regenerating muscles of young, adult, or old rats. It has been reported in a recent review that the physiological role of MRF4 remains unclear (23).
DISCUSSION
The novel finding in this study was that myogenin and MyoD mRNAs remained upregulated in bupivacaine-injected muscles of old rats compared with those of young and adult rats. Although not mutually exclusive, the expression of MyoD mRNA has been related to proliferation of satellite cells, whereas myogenin mRNA expression has been related to muscle differentiation and expression of muscle-specific proteins (26). Thus it is paradoxical that the mRNA expression of MyoD and myogenin remains elevated during impaired regeneration. The persistent elevation of myogenic factor mRNA levels may reflect a continued attempt to form new muscle cells. Negative feedback, which in regenerating muscles of the young rat downregulates IGF-I (22), MyoD, and myogenin mRNA (Figs. 2 and 3) levels to control values by day 14 to day 15 of recovery, does not seem to be present or is ineffective in regulating these mRNA levels in regenerating muscles of old rats. The IGF-I, MyoD, and myogenin gene products have been demonstrated to be critical for muscle cell determination, differentiation, and activation of muscle-specific gene expression (5, 20, 23, 26). However, there are many sites of protein regulation beyond mRNA levels, e.g., mRNA stability, translation efficiency, phosphorylation, and signal transduction targets, all of which may be modified within the aged muscle.
An alternative explanation is that a denervation-like phenomenon is responsible for the elevated MyoD and myogenin mRNAs. MyoD and myogenin mRNA levels are higher in embryonic muscle before its innervation and then are reexpressed at high levels in denervated adult muscles (9, 35). Therefore, it is possible that their prolonged expression during regeneration of old muscle could be related to incomplete reinnervation. Terminal nerve branches retract from the neuromuscular junction immediately after bupivacaine injection (32a), so a failure to reinnervate is possible. We have previously demonstrated that IGF-II mRNA levels are elevated at day 10 and are diminished by day 15 in regenerating muscles of young, adult, and old rats (22). Elevated levels of IGF-II mRNA after peripheral nerve damage return to control values once the nerve regrows and connects back to the muscle (27), which indirectly supports a successful reinnervation in regenerating muscles of old rats.
Limb muscles have been reported to regenerate less well in old compared with young mammals (3, 4, 32, 38). However, recovery from bupivacaine varies between dorsiflexor muscles of older animals. The extensor digitorum longus (EDL) muscle recovers better from bupivacaine-induced damage than the tibialis anterior muscle, even though they have similar functions and are composed of predominantly fast-twitch fiber types. The bupivacaine-injected tibialis anterior of 18-mo-old rats had not recovered muscle wet weight by 56 days (Fig. 1), whereas the EDL had recovered its muscle wet weight by 28 days (data not shown). This concurs with previous reports of complete recovery of EDL muscle wet weight and force at 60 days in young and old rats (4) and with unsuccessful regeneration of muscle fibers in the tibialis anterior of old rats after bupivacaine injection (Ref. 32; see also RESULTS). Inherent differences likely exist between the tibialis anterior and the EDL muscles to account for this discrepancy in regenerative capacity. One potential explanation for this difference could be the success of reinnervation (4). Although axonal regeneration does not need to occur in bupivacaine-injected muscles, neuromuscular synapses must be reformed between the retracted terminal nerves and the myotubes regenerating within the basal laminae (32a). The reformation of synapses in bupivacaine-injected EDL muscles may be superior to that occuring in the tibialis anterior.
During embryonic development of muscle, expression of myogenin and MyoD mRNA is elevated. Myogenin and MyoD mRNA levels then decrease from embryonic day 19 to an almost undetectable signal in muscles of young rats (3) and mice (2, 7, 9). In contrast, MRF4 mRNA expression increases postnatally until it is the dominantly expressed myogenic factor in adult muscle (2, 7, 9). Myogenin and MyoD mRNA levels were thought to remain low throughout adulthood; however, myogenin and MyoD mRNA levels in old mouse muscle are increased to levels similar to those in the newborn (25). Our present results confirm elevated myogenin and MyoD mRNA levels with aging, but we also observed an increased MRF4 mRNA expression in old rat muscle. Thus both embryonic myogenesis and senescence of skeletal muscle are associated with an increased expression of mRNAs for myogenin and MyoD. A loss of motoneurons occurs with aging (18) and results in denervated muscle fibers in old muscle. Denervation and/or electrical inactivity increases myogenin, MyoD, and MRF4 mRNA expression in skeletal muscle (9, 35), whereas electrical stimulation of denervated muscle represses myogenin and MyoD mRNA expression (9). Therefore, it is possible that alterations at the neuromuscular junction and/or the physical inactivity of old rats could be causative of the increased myogenin, MyoD, and MRF4 mRNA levels in muscles of old rats.
In summary, myogenin, MyoD, and MRF4 mRNAs demonstrated distinct patterns of expression during regeneration of skeletal muscle after bupivacaine injection. Aging had a pronounced effect on the temporal pattern of myogenin and MyoD mRNA expression but had no effect on MRF4 mRNA expression during regeneration. The prolonged elevation of myogenin and MyoD mRNA expression in regenerating muscles of old rats is a novel finding. Regeneration of growing muscle in young rats was accompanied by transient elevations of myogenin and MyoD mRNA expression and complete recovery of muscle mass. Regeneration of nongrowing and atrophic muscle in adult and old rats, respectively, was accompanied by a prolonged elevation of myogenin and MyoD (old rats only) mRNA expression and incomplete recovery of muscle mass. Thus the regenerative capacity of skeletal muscle is reduced with maturation concomitant with alterations in the regulation of myogenin mRNA, whereas alterations of MyoD mRNA regulation occur with senescence. The results of the present study demonstrate that a deficiency in myogenesis is at least partly accountable for the poor regeneration of the tibialis anterior muscle observed in old rats. Furthermore, elevated MyoD and myogenin mRNA levels in old control muscle may reflect a continued attempt to generate new muscle fibers and ameliorate muscle atrophy.
ACKNOWLEDGEMENTS
We thank Drs. Brian Black, Eric Olson, and Woodwring Wright for generosity in supplying probes.
FOOTNOTES
Address for reprint requests: F. W. Booth, Dept. of Integrative Biology, Pharmacology and Physiology, Univ. of Texas Medical School, 6431 Fannin St., Houston, Texas 77030 (E-mail: fbooth{at}girch1.med.uth.tmc.edu).
Received 27 January 1997; accepted in final form 16 May 1997.
REFERENCES
| 1. |
Brennan, T. J.,
and
E. N. Olson.
Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element on heterodimerization.
Genes Dev.
4:
582-595,
1990 |
| 2. |
Buonanno, A.,
L. Apone,
M. I. Morasso,
R. Beers,
H. R. Brenner,
and
R. Eftimie.
The MyoD family of myogenic factors is regulated by electrical activity: isolation and characterization of a mouse Myf-5 cDNA.
Nuc. Acids Res.
20:
539-544,
1992 |
| 3. |
Carlson, B. M.,
and
J. A. Faulkner.
Muscle transplantation between young and old rats: age of host determined functional recovery.
Am. J. Physiol.
256 (Cell Physiol. 25):
C1262-C1266,
1989 |
| 4. | Carlson, B. M., and J. A. Faulkner. The regeneration of noninnervated muscle grafts and Marcaine-treated muscles in young and old rats. J. Gerontol. A Biol. Sci. Med. Sci. 51: B43-B49, 1996[Abstract]. |
| 5. |
Carson, J. A.,
Z. Yan,
F. W. Booth,
M. E. Coleman,
R. J. Schwartz,
and
C. S. Stump.
Regulation of skeletal  -actin promoter in young chickens during hypertrophy caused by stretch overload.
Am. J. Physiol.
268 (Cell Physiol. 37):
C918-C924,
1995 |
| 6. | Chomczynski, P., and N. Sacchi. Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162: 156-159, 1987[Medline]. |
| 7. |
Duclert, A.,
J. Piette,
and
J.-P. Changeux.
Influence of innervation of myogenic factors and acetylcholine receptor -subunit mRNAs.
Neuroreport
2:
25-28,
1991[Medline].
|
| 8. |
Edmondson, D. G.,
and
E. N. Olson.
A gene with homology to the myc similarity region is expressed during myogenesis and is sufficient to activate the muscle differentiation program.
Genes Dev.
3:
628-640,
1989 |
| 9. |
Eftimie, R.,
H. R. Brenner,
and
A. Buonanno.
Myogenin and MyoD join a family of skeletal muscle genes regulated by electrical activity.
Proc. Natl. Acad. Sci. USA
88:
1349-1353,
1991 |
| 11. |
Florini, J. R.,
D. Z. Ewton,
and
S. A. Coolican.
Growth hormone and the insulin-like growth factor system in myogenesis.
Endocr. Rev.
17:
481-517,
1996 |
| 12. |
Florini, J. R.,
and
K. A. Magri.
Effects of growth factors on myogenic differentiation.
Am. J. Physiol.
256 (Cell Physiol. 25):
C701-C711,
1989 |
| 13. | Füchtbauer, E.-M., and H. Westphal. MyoD and myogenin are coexpressed in regenerating skeletal muscle of the mouse. Dev. Dyn. 193: 34-39, 1992[Medline]. |
| 14. | Grounds, M. D. Towards understanding skeletal muscle regeneration. Pathol. Res. Pract. 187: 1-22, 1991[Medline]. |
| 15. | Grounds, M. D., K. L. Garrett, M. C. Lai, W. E. Wright, and M. W. Beilharz. Identification of skeletal muscle precursor cells in vivo by use of MyoD and myogenin probes. Cell Tissue Res. 267: 99-104, 1992[Medline]. |
| 16. | Hall-Craggs, E. C. B. Rapid degeneration and regeneration of a whole skeletal muscle following treatment with bupivacaine (Marcain). Exp. Neurol. 43: 349-358, 1974. [Medline] |
| 17. |
Hamilton, M. T.,
D. R. Marsh,
D. S. Criswell,
W. Lou,
and
F. W. Booth.
No effect of aging on skeletal muscle insulin-like growth factor mRNAs.
Am. J. Physiol.
269 (Regulatory Integrative Comp. Physiol. 38):
R1183-R1188,
1995 |
| 18. | Hashizume, K., K. Kanda, and R. E. Burke. Medial gastrocnemius motor nucleus in the rat: age-related changes in the number and size of motoneurons. J. Comp. Neurol. 269: 425-430, 1988[Medline]. |
| 19. | Hasty, P., A. Bradley, J. H. Morris, D. G. Edmondson, J. M. Venuti, E. N. Olson, and W. H. Klein. Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature 364: 501-506, 1993[Medline]. |
| 20. |
Lefaucheur, J.-P.,
and
A. Sébille.
Muscle regeneration following injury can be modified in vivo by immune neutralization of basic fibroblast growth factor, transforming growth factor  1 or insulin-like growth factor I.
J. Neuroimmunol.
57:
85-91,
1995[Medline].
|
| 21. | Loughna, P. T., and C. Brownson. Two myogenic regulatory factor transcripts exhibit muscle-specific responses to disuse and passive stretch in adult rats. FEBS Lett. 390: 304-306, 1996[Medline]. |
| 22. |
Marsh, D. R.,
D. S. Criswell,
M. T. Hamilton,
and
F. W. Booth.
Association of insulin-like growth factor mRNAs expression with muscle regeneration in young, adult, and old rats.
Am. J. Physiol.
273 (Regulatory Integrative Comp. Physiol. 42):
R353-R358,
1997 |
| 23. | Megeney, L. A., and M. A. Rudnicki. Determination versus differentiation and the MyoD family of transcription factors. Biochem. Cell Biol. 73: 723-732, 1995[Medline]. |
| 23a. | Munro, H. N., and A. Fleck. Analysis of tissues and body fluids for nitrogenous constituents. In: Mammalian Protein Metabolism. New York: Academic, 1969, vol. III, p. 481-483. |
| 24. | Murre, C., P. S. McCaw, H. Vaessin, M. Caudy, L. Y. Jan, J. N. Yan, C. V. Cabrera, J. N. Buskin, S. D. Hauschka, A. B. Lassar, H. Weintraub, and D. Baltimore. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58: 537-544, 1989[Medline]. |
| 25. | Musaró, A., M. G. Cusella De Angelis, A. Germani, C. Ciccarelli, M. Molinaro, and B. M. Zani. Enhanced expression of myogenic regulatory genes in aging skeletal muscle. Exp. Cell Res. 221: 241-248, 1995[Medline]. |
| 26. |
Olson, E. N.,
and
W. H. Klein.
bHLH factors in muscle development: dead lines and commitments, what to leave in and what to leave out.
Genes Dev.
8:
1-8,
1994 |
| 27. | Pu, S. F., H. X. Zhuang, and D. N. Ishii. Differential spatio-temperal expression of the insulin-like growth factor genes in regenerating sciatic nerve. Brain Res. Mol. Brain Res. 34: 18-28, 1995[Medline]. |
| 28. | Rantanen, J., T. Hurme, R. Lukka, J. Heino, and H. Kalimo. Satellite cell proliferation and the expression of myogenin and desmin in regenerating skeletal muscle: evidence for two different populations of satellite cells. Lab. Invest. 72: 341-347, 1995[Medline]. |
| 29. | Rosenblatt, J. D. A time course study of the isometric contractile properties of rat extensor digitorum longus muscle injected with bupivacaine. Comp. Biochem. Physiol. A Physiol. 101A: 361-367, 1992. |
| 30. | Rosenblatt, J. D., and R. I. Woods. Hypertrophy of rat extensor digitorum longus muscle injected with bupivacaine. A sequential histochemical, immunohistochemical, histological and morphometric study. J. Anat. 181: 11-27, 1992. |
| 31. | Rudnicki, M. A., P. N. J. Schnegelsberg, R. H. Stead, T. Braun, H. H. Arnold, and R. R. Jaenisch. MyoD of Myf-5 is required for the formation of skeletal muscle. Cell 75: 1351-1359, 1993[Medline]. |
| 32. | Sachs, M. Effects of aging on skeletal muscle regeneration. J. Neurol. Sci. 87: 67-74, 1988. [Medline] |
| 32a. | Tomas i Ferré, J., R. Fenoll, I. Brunet, M. Santafé, and E. Mayayo. Changes in motor nerve terminals during bupivacaine-induced postsynaptic deprivation. J. Anat. 162: 225-234, 1989[Medline]. |
| 33. | Ullman, M., A. Ullman, H. Sommerland, A. Skottner, and A. Oldfors. Effects of growth hormone on muscle regeneration and IGF-I concentration in old rats. Acta Physiol. Scand. 140: 521-525, 1990[Medline]. |
| 34. | Vandenburgh, H. H., M. F. Sheff, and S. I. Zacks. Soluble age-related factors from skeletal muscle which influence muscle development. Exp. Cell Res. 153: 389-340, 1984[Medline]. |
| 35. | Voytik, S. L., M. Przyborski, S. F. Badylak, and S. F. Konieczny. Differential expression of muscle regulatory factor genes in normal and denervated adult rat hindlimb muscles. Dev. Dyn. 198: 214-224, 1993[Medline]. |
| 36. | Witzemann, V., and B. Sakmann. Differential regulation of MyoD and myogenin mRNA levels by nerve induced muscle activity. FEBS Lett. 282: 259-264, 1991[Medline]. |
| 37. | Wright, W. E., D. A. Sassoon, and V. K. Lin. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell 56: 607-617, 1989[Medline]. |
| 38. | Zacks, S. I., and M. F. Sheff. Age-related regeneration of mouse minced anterior tibial muscle. Muscle Nerve 5: 152-161, 1982[Medline]. |
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C. Suetta, L. G. Hvid, L. Justesen, U. Christensen, K. Neergaard, L. Simonsen, N. Ortenblad, S. P. Magnusson, M. Kjaer, and P. Aagaard Effects of aging on human skeletal muscle after immobilization and retraining J Appl Physiol, October 1, 2009; 107(4): 1172 - 1180. [Abstract] [Full Text] [PDF]
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 D. T. Hwee and S. C. Bodine Age-Related Deficit in Load-Induced Skeletal Muscle Growth J Gerontol A Biol Sci Med Sci, June 1, 2009; 64A(6): 618 - 628. [Abstract] [Full Text] [PDF]
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D. J. Kosek and M. M. Bamman Modulation of the dystrophin-associated protein complex in response to resistance training in young and older men J Appl Physiol, May 1, 2008; 104(5): 1476 - 1484. [Abstract] [Full Text] [PDF]
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M. I. Lewis, M. Fournier, T. W. Storer, S. Bhasin, J. Porszasz, S.-G. Ren, X. Da, and R. Casaburi Skeletal muscle adaptations to testosterone and resistance training in men with COPD J Appl Physiol, October 1, 2007; 103(4): 1299 - 1310. [Abstract] [Full Text] [PDF]
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D. J. Kosek, J.-s. Kim, J. K. Petrella, J. M. Cross, and M. M. Bamman Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults J Appl Physiol, August 1, 2006; 101(2): 531 - 544. [Abstract] [Full Text] [PDF]
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U. Raue, D. Slivka, B. Jemiolo, C. Hollon, and S. Trappe Myogenic gene expression at rest and after a bout of resistance exercise in young (18-30 yr) and old (80-89 yr) women J Appl Physiol, July 1, 2006; 101(1): 53 - 59. [Abstract] [Full Text] [PDF]
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 S. J. Lees, C. R. Rathbone, and F. W. Booth Age-associated decrease in muscle precursor cell differentiation Am J Physiol Cell Physiol, February 1, 2006; 290(2): C609 - C615. [Abstract] [Full Text] [PDF]
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M. M. Bamman, R. C. Ragan, J.-s. Kim, J. M. Cross, V. J. Hill, S. C. Tuggle, and R. M. Allman Myogenic protein expression before and after resistance loading in 26- and 64-yr-old men and women J Appl Physiol, October 1, 2004; 97(4): 1329 - 1337. [Abstract] [Full Text] [PDF]
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 M. I. Lewis, M. Fournier, X. Da, H. Li, Z. Mosenifar, R. J. McKenna Jr, and A. H. Cohen Short-term Influences of Lung Volume Reduction Surgery on the Diaphragm in Emphysematous Hamsters Am. J. Respir. Crit. Care Med., October 1, 2004; 170(7): 753 - 759. [Abstract] [Full Text] [PDF]
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J. C. Gallegly, N. A. Turesky, B. A. Strotman, C. M. Gurley, C. A. Peterson, and E. E. Dupont-Versteegden Satellite cell regulation of muscle mass is altered at old age J Appl Physiol, September 1, 2004; 97(3): 1082 - 1090. [Abstract] [Full Text] [PDF]
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P. M. Siu, D. A. Donley, R. W. Bryner, and S. E. Alway Myogenin and oxidative enzyme gene expression levels are elevated in rat soleus muscles after endurance training J Appl Physiol, July 1, 2004; 97(1): 277 - 285. [Abstract] [Full Text] [PDF]
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 J. S. Pattison, L. C. Folk, R. W. Madsen, T. E. Childs, and F. W. Booth Transcriptional profiling identifies extensive downregulation of extracellular matrix gene expression in sarcopenic rat soleus muscle Physiol Genomics, September 29, 2003; 15(1): 34 - 43. [Abstract] [Full Text] [PDF]
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N. Psilander, R. Damsgaard, and H. Pilegaard Resistance exercise alters MRF and IGF-I mRNA content in human skeletal muscle J Appl Physiol, September 1, 2003; 95(3): 1038 - 1044. [Abstract] [Full Text] [PDF]
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W. J. Lee, J. McClung, G. A. Hand, and J. A. Carson Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate J Appl Physiol, March 1, 2003; 94(3): 1153 - 1161. [Abstract] [Full Text] [PDF]
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 M Hameed, R W Orrell, M Cobbold, G Goldspink, and S D R Harridge Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise J. Physiol., February 15, 2003; 547(1): 247 - 254. [Abstract] [Full Text] [PDF]
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 M. M. Bamman, V. J. Hill, G. R. Adams, F. Haddad, C. J. Wetzstein, B. A. Gower, A. Ahmed, and G. R. Hunter Gender Differences in Resistance-Training-Induced Myofiber Hypertrophy Among Older Adults J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2003; 58(2): B108 - 116. [Abstract] [Full Text] [PDF]
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B. M. Carlson, A. B. Borisov, E. I. Dedkov, A. Khalyfa, T. Y. Kostrominova, P. C. D. Macpherson, E. Wang, and J. A. Faulkner Effects of Long-Term Denervation on Skeletal Muscle in Old Rats J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2002; 57(10): B366 - 374. [Abstract] [Full Text] [PDF]
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S. M. Roth, R. E. Ferrell, D. G. Peters, E. J. Metter, B. F. Hurley, and M. A. Rogers Influence of age, sex, and strength training on human muscle gene expression determined by microarray Physiol Genomics, September 3, 2002; 10(3): 181 - 190. [Abstract] [Full Text] [PDF]
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J. A. Carson, W. J. Lee, J. McClung, and G. A. Hand Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic steroid administration J Appl Physiol, July 1, 2002; 93(1): 242 - 250. [Abstract] [Full Text] [PDF]
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S. E. Alway, H. Degens, G. Krishnamurthy, and C. A. Smith Potential role for Id myogenic repressors in apoptosis and attenuation of hypertrophy in muscles of aged rats Am J Physiol Cell Physiol, July 1, 2002; 283(1): C66 - C76. [Abstract] [Full Text] [PDF]
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 S. E. Alway, H. Degens, D. A. Lowe, and G. Krishnamurthy Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R411 - R422. [Abstract] [Full Text] [PDF]
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P. Hespel, B. Op't Eijnde, M. V. Leemputte, B. Urso, P. L Greenhaff, V. Labarque, S. Dymarkowski, P. V. Hecke, and E. A Richter Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans J. Physiol., October 15, 2001; 536(2): 625 - 633. [Abstract] [Full Text] [PDF]
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 T. Launay, A.-S. Armand, F. Charbonnier, J.-C. Mira, E. Donsez, C. L. Gallien, and C. Chanoine Expression and Neural Control of Myogenic Regulatory Factor Genes During Regeneration of Mouse Soleus J. Histochem. Cytochem., July 1, 2001; 49(7): 887 - 900. [Abstract] [Full Text] [PDF]
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T. Y. Kostrominova, P. C. D. Macpherson, B. M. Carlson, and D. Goldman Regulation of myogenin protein expression in denervated muscles from young and old rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2000; 279(1): R179 - R188. [Abstract] [Full Text] [PDF]
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R. R. Gomes Jr. and F. W. Booth Expression of acetylcholine receptor mRNAs in atrophying and nonatrophying skeletal muscles of old rats J Appl Physiol, November 1, 1998; 85(5): 1903 - 1908. [Abstract] [Full Text] [PDF]
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D. A. Lowe, T. Lund, and S. E. Alway Hypertrophy-stimulated myogenic regulatory factor mRNA increases are attenuated in fast muscle of aged quails Am J Physiol Cell Physiol, July 1, 1998; 275(1): C155 - C162. [Abstract] [Full Text] [PDF]
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