Download Muscle-specific atrophy of the quadriceps femoris with aging

J Appl Physiol
90: 2070–2074, 2001.
Muscle-specific atrophy of the quadriceps femoris
with aging
T. A. TRAPPE,1 D. M. LINDQUIST,2 AND J. A. CARRITHERS1
1
Nutrition, Metabolism, and Exercise Laboratory, Donald W. Reynolds
Department of Geriatrics, and 2Department of Radiology, University of
Arkansas for Medical Sciences, Little Rock, Arkansas 72205
Received 14 December 2000; accepted in final form 17 January 2001
allows for the discrimination of the muscles of a specific
muscle group (e.g., the four muscles of the quadriceps
femoris).
The purpose of this study was to address the appropriateness of the vastus lateralis as a surrogate for the
quadriceps femoris in aging studies. Specifically, we
hypothesized that the vastus lateralis would atrophy to
the same degree as the other three muscles of the
quadriceps femoris in aging women and men.
METHODS
is composed of the rectus
femoris, vastus lateralis, vastus intermedius, and vastus medialis. However, the vastus lateralis muscle has
been used for nearly 40 yr to represent the quadriceps
femoris in human muscle physiology and biochemistry
studies (4–6). Many aerobic and resistance exercise
investigations have studied muscle samples from the
vastus lateralis while simultaneously examining function of the entire quadriceps femoris (1, 22, 23, 25).
This vastus lateralis-quadriceps femoris supposition is
also being used extensively in aging muscle research
(8–11, 13, 26). However, it has never been determined
whether all four muscles of the quadriceps femoris
change similarly with aging.
Recently, noninvasive measures such as computed
tomography (CT) and magnetic resonance imaging
(MRI) have allowed for the accurate determination of
muscle size (7, 15, 20). In particular, MRI resolution
Subjects. Ten young (5 male, 5 female) and ten old (5 male,
5 female) individuals were included in this investigation
(Table 1) after a physical examination that included blood
and urine analyses and an interview documenting the subject’s life history of physical activity. Subjects were excluded
if they had any acute or chronic illness, cardiac abnormalities, uncontrolled hypertension, insulin- or non-insulin-dependent diabetes, abnormal blood or urine chemistries, arthritis, or history of neuromuscular problems or if they
smoked cigarettes. Women taking oral contraceptives or hormone replacement therapy were included. It was our intent
to carefully screen the subjects so as to include lifelongsedentary, healthy older and younger individuals; therefore,
we excluded individuals who had ever completed any formal
exercise programs or physical activity outside of their activities of daily living. Body composition was determined using
whole body air displacement plethysmography (Life Measurement Instruments, Concord, CA) (14). All procedures,
risks, and benefits associated with the experimental testing
were explained to the subjects before they signed a consent
form adhering to the guidelines of the Institutional Review
Board of the University of Arkansas for Medical Sciences.
MRI. After 1 h of supine rest to control for the influence of
posturally related fluid shifts on muscle size (3), MRIs were
obtained for each subject. Subjects were supine, and their
heels were fixed on a nonmetallic support to control joint and
scan angle and to minimize compression of the legs against
each other and the MRI gurney. Imaging was completed in a
1.5-T GE Signa scanner (General Electric, Milwaukee, WI) to
determine the volume and cross-sectional area (CSA) of the
total quadriceps femoris, rectus femoris (RF), vastus lateralis
(VL), vastus intermedius (VI), and vastus medialis (VM). A
coronal scout scan [repetition time/echo time (TR/TE) ⫽ 300/
14, field of view 48, 256 ⫻ 160 matrix] of ⬃5 slices of 5 cm
Address for reprint requests and other correspondence: T. A. Trappe,
Nutrition, Metabolism, and Exercise Laboratory, DWR Center on Aging, Univ. of Arkansas for Medical Sciences, 4301 W. Markham, Slot
806, Little Rock, AR 72205 (E-mail: [email protected]).
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.
magnetic resonance imaging; rectus femoris; vastus lateralis;
vastus intermedius; vastus medialis
THE QUADRICEPS FEMORIS MUSCLE
2070
8750-7587/01 $5.00 Copyright © 2001 the American Physiological Society
http://www.jap.org
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Trappe, T. A., D. M. Lindquist, and J. A. Carrithers.
Muscle-specific atrophy of the quadriceps femoris with aging.
J Appl Physiol 90: 2070–2074, 2001.— We examined the size
of the four muscles of the quadriceps femoris in young and old
men and women to assess whether the vastus lateralis is an
appropriate surrogate for the quadriceps femoris in human
studies of aging skeletal muscle. Ten young (24 ⫾ 2 yr) and
ten old (79 ⫾ 7 yr) sedentary individuals underwent magnetic resonance imaging of the quadriceps femoris after 60
min of supine rest. Volume (cm3) and average cross-sectional
area (CSA, cm2) of the rectus femoris (RF), vastus lateralis
(VL), vastus intermedius (VI), vastus medialis (VM), and the
total quadriceps femoris were decreased (P ⬍ 0.05) in older
compared with younger women and men. However, percentage of the total quadriceps femoris taken up by each muscle
was similar (P ⬎ 0.05) between young and old (RF: 10 ⫾ 0.3
vs. 11 ⫾ 0.4; VL: 33 ⫾ 1 vs. 33 ⫾ 1; VI: 31 ⫾ 1 vs. 31 ⫾ 0.4;
VM: 26 ⫾ 1 vs. 25 ⫾ 1%). These results suggest that each of
the four muscles of the quadriceps femoris atrophy similarly
in aging men and women. Our data support the use of vastus
lateralis tissue to represent the quadriceps femoris muscle in
aging research.
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AGING AND MUSCLE-SPECIFIC ATROPHY
Table 1. Subject characteristics
Age, yr
Height, cm
Weight, kg
Body Fat, %
Young
Old
24 ⫾ 2 (22–27)
79 ⫾ 7 (72–93)
173 ⫾ 9 (160–188)
167 ⫾ 10 (150–182)
67.8 ⫾ 12.3 (49.7–89.4)
71.5 ⫾ 7.8 (58.3–83.9)
23 ⫾ 8 (12–37)
35 ⫾ 11 (18–51)*
YM
OM
YF
OF
24 ⫾ 2 (22–27)
81 ⫾ 8 (73–93)
24 ⫾ 2 (22–26)
77 ⫾ 6 (72–86)
180 ⫾ 6 (175–188)
175 ⫾ 5 (170–182)
165 ⫾ 3 (160–168)
158 ⫾ 6 (150–163)
77.4 ⫾ 8.2 (67.0–89.4)
74.6 ⫾ 5.7 (69.0–83.9)
58.2 ⫾ 6.6 (49.7–66.6)
68.5 ⫾ 9.1 (58.3–83.1)
20 ⫾ 7 (12–31)
25 ⫾ 5 (18–30)
27 ⫾ 9 (15–37)
44 ⫾ 6 (36–51)
Values are means ⫾ SD. n ⫽ 10 in young (Y) and old (O) groups; 5 men (M) and 5 women (F). Nos. in parentheses are range. * Different
(P ⬍ 0.05) from young group.
RESULTS
Both the volume and average CSA decreased from
young to old in the individual muscles and the whole
quadriceps femoris (Tables 2 and 3). However, the
percentage (volume or average CSA) of the quadriceps
that each muscle comprised was unchanged with aging
(Fig. 3). Figure 2 shows a representative MRI and CSA
data from an old and young subject.
DISCUSSION
Two important findings in the present study support
the use of the VL as a surrogate of the quadriceps
femoris in studies of aging skeletal muscle. First, significant differences existed between the old and young
in absolute size of each of the four quadriceps femoris
muscles (i.e., aging muscle atrophy). Second, the proportion of the total volume or area of the quadriceps
femoris that each of the four muscles comprises was
not different between old and young individuals. Taken
together, these two findings suggest that the four muscles that make up the quadriceps femoris likely atrophy to the same extent in aging men and women.
These findings are important when one considers the
large number of cross-sectional and longitudinal investigations of aging human skeletal muscle that have
used or are using the vastus lateralis muscle tissue to
represent the quadriceps femoris. For example, studies
have examined the CSA of muscle fibers from the
vastus lateralis of young to old individuals and then
compared these differences with knee extensor (quadriceps femoris) strength in the same individuals (12,
24). Other studies have examined the fractional synthetic rate of muscle proteins from vastus lateralis
biopsy tissue of 20- to 92-yr-old women and men and
related the differences to quadriceps femoris muscle
strength (2). From our data, it appears that these and
other similar comparisons are likely appropriate.
To our knowledge, no one has previously addressed
the issue presented in the present paper with a direct
Table 2. Volumes of the quadriceps femoris muscles
Young
Old
YM
OM
YF
OF
Rectus
Femoris
Vastus
Lateralis
Vastus
Intermedius
Vastus
Medialis
Total
85.3 ⫾ 7.4
66.8 ⫾ 5.1*
292.2 ⫾ 21.4
200.2 ⫾ 14.3*
277.3 ⫾ 28.1
192.2 ⫾ 15.0*
238.5 ⫾ 26.7
157.5 ⫾ 15.5*
893.4 ⫾ 81.1
616.6 ⫾ 47.7*
345.6 ⫾ 23.3
228.8 ⫾ 17.5
238.8 ⫾ 9.8
171.6 ⫾ 14.3
354.0 ⫾ 21.4
224.8 ⫾ 18.7
200.7 ⫾ 13.0
159.6 ⫾ 11.1
312.7 ⫾ 19.1
190.0 ⫾ 21.1
164.3 ⫾ 8.8
125.0 ⫾ 10.6
103.6 ⫾ 7.9
77.8 ⫾ 6.0
67.0 ⫾ 4.2
55.8 ⫾ 4.6
Values are means ⫾ SE in cm3. * Different (P ⬍ 0.05) from young group.
1115.8 ⫾ 66.5
721.4 ⫾ 57.7
670.9 ⫾ 20.5
511.9 ⫾ 37.9
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thick with 5-mm spacing was completed to establish orientation of the femur (Fig. 1). After the scout scan, interleaved
transaxial images of 1 cm thick (TR/TE ⫽ 2,000/9, field of
view 48 cm, 256 ⫻ 256 matrix) were taken from the top of the
greater trochanter of the femur to the articular surface of the
tibia (Fig. 2).
Magnetic resonance images were transferred electronically from the scanner to a personal computer (Macintosh
Power PC) and analyzed with NIH Image software (version
1.60) using manual planimetry. Analyses of the magnetic
resonance images began with the first proximal slice not
containing gluteal muscle and continued distally to the last
slice containing RF (7), because this region has been shown to
represent the maximal CSA of the thigh (17, 20). The dominant leg of each subject was analyzed for CSA and volume.
The average CSA (cm2) was taken as the average of all the
analyzed slices for an individual muscle and determined for
the RF, VL, VI, and VM and summed for the total quadriceps
femoris. Muscle volume (cm3) was calculated by multiplying
the CSA of each individual muscle by the slice thickness (1
cm) for all analyzed images of the RF, VL, VI, andVM and
summed for the total quadriceps femoris.
All measurements were made by the same investigator. In
our laboratory, coefficients of variation for measurements
made on separate days on the same individuals were 3.6, 1.4,
2.9, 2.6, and 1.4% for RF, VL, VI, VM, and total quadriceps
femoris, respectively. The coefficients of variation measuring
the same image were 0.3, 1.1, 0.2, 1.3, and 0.2% for RF, VL,
VI, and VM and total quadriceps femoris, respectively.
Statistics. A one-way analysis of variance was completed
on the group (men and women combined) data for subject
characteristics, individual muscle volume, and CSA of the
quadriceps femoris, and the percentage of the individual
muscle volume and CSA of the quadriceps femoris. Significance was accepted at P ⬍ 0.05.
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AGING AND MUSCLE-SPECIFIC ATROPHY
Table 3. Average cross-sectional areas of the
quadriceps femoris muscles
Rectus
Femoris
Vastus
Lateralis
Vastus
Intermedius
Vastus
Medialis
Total
Young 6.0 ⫾ 0.3 20.9 ⫾ 0.9 19.6 ⫾ 1.4 16.9 ⫾ 1.3 63.4 ⫾ 3.7
Old
5.0 ⫾ 0.3* 15.1 ⫾ 1.0* 14.5 ⫾ 1.0* 11.8 ⫾ 1.1* 46.4 ⫾ 3.4*
YM
OM
YF
OF
6.8 ⫾ 0.2
5.8 ⫾ 0.4
5.3 ⫾ 0.2
4.2 ⫾ 0.3
22.8 ⫾ 1.3
17.2 ⫾ 1.4
19.0 ⫾ 0.7
13.0 ⫾ 0.8
23.3 ⫾ 1.0
16.8 ⫾ 1.3
16.0 ⫾ 1.0
12.1 ⫾ 0.7
20.6 ⫾ 0.5
14.2 ⫾ 1.5
13.2 ⫾ 1.0
9.5 ⫾ 0.7
73.5 ⫾ 2.5
53.9 ⫾ 4.1
53.4 ⫾ 1.8
38.8 ⫾ 2.3
Values are means ⫾ SE in cm2. * Different (P ⬍ 0.05) from young
group.
or indirect sampling of all of the quadriceps femoris
muscles. However, we do recognize the underlying
methodological impediment as the basis for the lack of
relevant data. Recently, using similar MRI methodology to that used in the present study, it has been
shown, in a nonaging model of human muscle atrophy,
that the individual muscles of the quadriceps femoris
atrophy to varying degrees (27). Thus, in conjunction
with our ongoing studies of aging skeletal muscle, we
Fig. 2. Representative magnetic resonance images of an old and young subject. Left: a 77-yr-old man with an
average cross-sectional area (CSA) for the rectus femoris (RF) of 5.0 cm2 (9), vastus lateralis (VL) of 19.7 cm2 (35),
vastus intermedius (VI) of 16.7 cm2 (30), vastus medialis (VM) of 15.0 cm2 (27), and total of 56.4 cm2. Right: a
23-yr-old man with an average CSA for the RF of 6.2 cm2 (8), VL of 23.7 cm2 (31), VI of 24.7 cm2 (32), VM of 21.5
cm2 (28), and total of 76.2 cm2. Values in parentheses represent %CSA of the total quadriceps femoris.
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Fig. 1. Representative image of a coronal scout scan used for land
marking the femur (see METHODS).
thought it was necessary to address this issue in an
aging population.
Our data compare favorably with literature values of
total quadriceps femoris muscle size in young and old
(7, 10, 11, 15–17) and individual muscles of the quadriceps femoris from young subjects by means of MRI (7,
15, 17). Furthermore, the 27% difference in CSA
(⫺31% in volume) of the total quadriceps femoris from
young to old in the present study is comparable to
calculated differences in reported values from studies
that have examined only young (7, 15–17) or old individuals (10, 11).
The young and old study groups contained equal
numbers of men and women. However, we did not
power the study to examine gender responses as well
as aging responses. We have included the subset of
male and female data in Tables 1–3 to represent the
gender responses. These data show that the gender
response is similar to the group (men and women
combined) response. That is, the absolute size of the
muscles was smaller in both older women and men,
AGING AND MUSCLE-SPECIFIC ATROPHY
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Fig. 3. Percent volume (and CSA) of the individual muscles of the
quadriceps femoris.
The authors thank the subjects for their participation.
This work was supported by National Institutes of Health Grants
R21 AG-15833 and K01 AG-00831 (to T. Trappe) and M01 RR-14288.
Downloaded from http://jap.physiology.org/ by 10.220.33.3 on May 7, 2017
compared with their younger gender counterparts.
Furthermore, the percentage of the total quadriceps
femoris taken up by each muscle was similar in both
women and men with aging.
In presenting these data, we realize that specific
biochemical, molecular, or physiological analyses were
not completed on tissue obtained from each muscle of
the quadriceps femoris from our subjects. One further
consideration when interpreting our data is the possibility of age-related increases in nonmuscle (i.e., fat
and connective) tissue. It has been shown that the
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Other methodologies are needed to address the issue
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due to location or size. Promising approaches for the
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tomography (18, 28). Both of these methods allow for
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In conclusion, the present data support the continued use of the vastus lateralis as a surrogate for the
quadriceps femoris in studies of aging human skeletal
muscle. Future studies of muscle samples, or other
innovative measurements, taken from more than one
muscle of the quadriceps femoris in cross-sectional and
longitudinal studies of aging would further help address this issue.
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