Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

FP5

BETTER-AGEING Berichtzusammenfassung

Project ID: QLK6-CT-2001-00323
Gefördert unter: FP5-LIFE QUALITY
Land: Italy

Skeletal muscle oxidative metabolism and exercise tolerance in ageing

Central (cardiopulmonary) and peripheral (at the skeletal muscle level) effects of ageing on muscle oxidative metabolism were evaluated in this study.

A proteomic analysis of skeletal muscle samples was conducted by two-dimensional differential gel electrophoresis (2-DIGE), SDS analysis and subsequent identification of differently expressed proteins. The results show, in the elderly (E) vs. the young (Y): a downregulation of the degree of expression and phosphorylation of the regulatory isoforms of myosin light chains (MLC); myosin heavy chains (MHC) concentration characterised by greater MHC 1 and 2A; higher concentration of several oxidative enzymes, and lower concentrations of several anaerobic enzymes. The findings on MLC phosphorylation could explain, at least in part, the functional deterioration of ageing skeletal muscle. Ageing skeletal muscle, however, seems to show a shift towards a more oxidative phenotype, whose potential might be not fully expressed in normal conditions.

E showed a significant decline (about 50%) of peak (the value determined at voluntary exhaustion) maximal aerobic power (VO2peak), as well as of the ventilatory threshold (VT) with respect to Y. The lower VO2peak was associated with lower HRpeak and with a lower maximal O2 extraction by skeletal muscle (O2 extraction was estimated at the level of the vastus lateralis by Near Infrared Spectroscopy [NIRS]). Arterial blood O2 saturation (SaO2) did not significantly decrease, both in E and Y. Thus, during cycloergometric exercise both central (but not pulmonary) and peripheral factors contributed to the lower VO2peak in E.
Incremental exercises were also conducted by utilizing a protocol in which only relatively small (2-3 kg) muscle masses were involved, assuming that cardiopulmonary factors should not significantly contribute to the reduced aerobic performance. Knee extension exercises were conducted at 20%, 40% and 60% (3-min steps) of the force corresponding to 1 repetition maximum (1 RM). 1RM and the total lifted load were significantly (by about 40-50%) lower in E vs. Y. In both groups HRpeak was significantly lower that the HRpeak determined during cycloergometric exercise, confirming that the knee-extension exercise did not represent a significant burden for the cardiovascular system. Peak O2 extraction estimated by NIRS was higher in E vs. Y. Thus, after presumably allowing a better perfusion of the exercising muscles, E were capable to attain a higher O2 extraction than Y.

During constant-load cycloergometric exercise below and above VT, O2 uptake (VO2) kinetics were significantly slower in E vs. Y. A slower VO2 kinetics negatively affects exercise tolerance, and is generally considered a variable of evaluation of oxidative metabolism in skeletal muscle. The slower VO2 kinetics in E was associated with slower O2 extraction kinetics. During exercise above VT E did not show, differently from Y, a slow component of VO2 kinetics, and presented less muscle fatigue (as determined by electromyography [EMG], evaluating the slopes of the Root Mean Square [RMS] vs. time profiles). The occurrence of a VO2 slow component is considered to be negative for exercise tolerance, and it is thought to derive from the recruitment of less efficient fast fibres. Thus, not only E showed VT at a higher percentage of their VO2peak, compared to Y, but were also capable to sustain constant-load exercise above VT without showing a slow component of VO2 and with less EMG signs of fatigue.

The subjects underwent a 1-year training program (T), mainly characterised by strength training, with some aerobic exercises. T determined in E a significant increase in HRpeak, a tendency towards an increase in VO2peak, and an increase in maximal O2 extraction. Pulmonary VO2 kinetics were unaffected by training.
As for the knee-extensor exercise, T in E determined a trend toward an increase in the total lifted load, an increased O2 extraction and less EMG signs of fatigue during the exhausting load. The relatively small effects of T on oxidative metabolism could be attributed to the low amount of aerobic work in the training sessions.

In conclusion, there is a significant functional limitation of oxidative metabolism in ageing muscle, attributable to both central and peripheral factors. However, there could be a significant hidden oxidative potential in ageing muscle (see oxidative enzymes by the proteomic analysis, as well as the higher percentage of type 1 and 2A fibres), as also suggested by some functional variables (e.g. higher VT, no slow component, less fatigue during constant-load exercise >VT, higher O2 extraction during knee-extension). Some effects of training were observed (e.g. slightly higher VO2peak, HRpeak, peak O2 extraction during cycloergometric exercise; less fatigue during knee-extension exercise), even if the training protocol was not specific for aerobic metabolism.

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Kontakt

Bruno GRASSI, (Associate Professor)
Tel.: +39-025-0330421
Fax: +39-025-0330414
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