Ariel C. Zane1, Donnie Cameron1, Seongjin Choi1, David A. Reiter2, Kenneth W. Fishbein2, Christopher M. Bergeron1, Eleanor Simonsick1, Richard G. Spencer2, and Luigi Ferrucci3
1Translational Gerontology Branch, NIH/National Institute on Aging, Baltimore, MD, United States, 2Laboratory of Clinical Investigation, NIH/National Institute on Aging, Baltimore, MD, United States, 3Intramural Research Program, NIH/National Institute on Aging, Baltimore, MD, United States
Synopsis
We examined the effect of high intensity physical activity
on the post-exercise PCr recovery rate (kPCr), testing whether the
decline in muscle quality may be attributed to an age-related decline in muscle
mitochondrial capacity. In-vivo 31P MRS measurements were
obtained before, during, and after a rapid knee-extension exercise. The
cross-sectional results in the BLSA show that both age and frequency of
physical activity are significant predictors of kPCr. However,
neither is significantly correlated with a strength-based assessment of muscle
quality.Purpose
To examine the effect of high intensity physical activity on
the post-exercise PCr recovery rate (k
PCr), and test the hypothesis
that the decline of muscle quality may be attributed to an age-related decline
in muscle mitochondrial energetic capacity.
Methods
We investigated the relationship between the post-exercise
phosphocreatine (PCr) recovery rate (kPCr), and measures of muscle
quality in the Baltimore Longitudinal Study of Aging (BLSA) participants (n =
258, age = 72 ± 13 years, male = 120, female = 138). In-vivo 31P MRS measurements were obtained using a 3T Philips Achieva MR scanner (Philips, Best,
The Netherlands) and a 10-cm 31P-tuned surface coil (PulseTeq,
Surrey, United Kingdom) fastened over the left thigh vastus lateralis muscle; participants
performed a rapid ballistic knee extension exercise while lying supine in the
bore of the magnet, following a protocol similar to that outlined by Coen et al.1
A series of pulse-acquire 31P spectra were obtained before, during,
and after the knee extension exercise. The pulse sequence consisted of adiabatic
RF excitation pulses with a 90-degree flip angle, TR = 1.5 s, averaged over
four scans, with 6 s between consecutive time points. A total of 75 dynamic
time points were acquired, for a total of 7.5 minutes scan time. The duration
of exercise was monitored to achieve between a 33 – 66% reduction in PCr signal
amplitude; spectra were processed using jMRUI (version 5.0), and quantified
using a nonlinear least squares algorithm (AMARES).2,3 The recovery
rate for phosphocreatine was calculated by fitting the time-dependent change in
[PCr] to a mono-exponential function of the form PCr(t) = PCr(0) + {PCrrest
– PCr(0)}{1 – exp(-t/ τPCr)};
kPCr, the recovery rate constant is defined as 1/ τPCr
and is accepted as a marker of mitochondrial oxidative capacity.4
One functional metric of muscle quality (Nm/cm2)
is defined as the ratio between knee-extension isokinetic strength (isokinetic
dynamometer, 30 deg/s), and thigh muscle cross-sectional area (CMA) as measured
by CT (computed topography). To account for variations in subject height, we
define a normalized CMA, NCMA = [(CMAx/(hx)2]*(hmean)2,
where CMAx and hx denote the CMA and height,
respectively, for the xth subject, and hmean is the
average height from all subjects in the population. Muscle quality is defined
by NNMQ = isokinetic peak torque/NCMA.5
The amount of high intensity exercise is defined by the
self-reported number of minutes per week spent participating in a high
intensity physical activity.
Results and Discussion
The cross-sectional results from the BLSA show that the PCr
recovery rate decreases with increasing age (Figure 1), but, along with age,
the frequency of high intensity exercise per week is a significant predictor of
kPCr in both genders, when adjusting for age, height, and weight
(Table 1), suggesting that the amount of intense physical activity modulates the
mitochondrial oxidative capacity of skeletal muscle.
Muscle quality, NNMQ, has previously been shown
to decline with age; that relationship is demonstrated here again (Table 2).5
However, when adjusting for age and weight (NNMQ is already
normalized by height), kPCr does not appear as a significant
predictor of muscle quality in either gender. A linear regression model for NNMQ
was fit for predictors including age, weight, frequency of high intensity
exercise and kPCr; neither the exercise variable nor kPCr
were significant (data not shown). These
results suggest that while bioenergetic capacity in skeletal muscle can be increased
by high levels of activity, kPCr does not act as a limiting factor
for max knee extension torque. This work will be extended using other
biochemical and functional measures available through the BLSA in an effort to
further define the elements of the decline in physical function with age.
Conclusions
Age and frequency of high intensity exercise are predictors
of the PCr recovery rate in both genders; frequency of high intensity physical
activity appears to be positively correlated with k
PCr in men, and negatively
correlated with k
PCr in women. However, k
PCr is not
strongly associated with assessments of strength-defined muscle quality in
either gender.
Acknowledgements
This research was supported entirely the Intramural Research Program of the NIH, National Institute on Aging.References
1. Coen PM, Jubrias SA, Distefano G, et al. Skeletal Muscle Mitochondrial Energetics Are Associated With Maximal Aerobic Capacity and Walking Speed in Older Adults. J. Gerontol A Biol Sci Med Sci. 2013; 68(4):447-455.
2. Naressi A, Couturier C, Castang I, et al. Java-based graphical user interface for MRUI, a softwarepackage for quantitation of in vivo=medical magnetic resonance spectroscopy signals. Comput
Biol Med. 2001; 31: 269-286
3. Vanhamme L, Van Huffel S, Van Hecke P, et al. Time-domain quantification of series of biomedical magnetic resonance spectroscopy signals. J. Magn. Reson. 1999; 140: 120-130.
4. Conley K, Jubrias SA, Esselman PC. Oxidative capacity and aging in human muscle. J. Physiol. 2000; 526: 203-210.
5. Moore AZ, Caturegli G, Metter EJ, et al. Difference in muscle quality over the adult life span and biological correlates in the Baltimore Longitudinal Study of Aging. J Amer Geriatr Soc 2014; 62: 230-236.