Age-related changes in muscle energetics
20 important questions on Age-related changes in muscle energetics
The muscle is a metabolically active tissue, what is needed for this
- especially during contractions...
- some approcimate values:
- brain - 3 ml/min/100g
- kidney - 5
- skin - 0.2
- heart - 8
- skeletal muscle (rest) - 1
- skeletal muscle (contraction) - 50
Most ATP is generated in mitochondria, in 2 successive processes, namely
- Citric acid cycle (or Krebs cycle)
- Oxidative phosphorylation
What happens with the VO2max when ageing?
- Maximal oxygen consumption (VO2max): O2 consumption at maximal exercise intensity
- measure of endurance
exercise capacity
- Declines with ageing
- This parallels a decline in maximal heart rate
- "220 - age"
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Are muscle mitochondria involved in the age-related decline in VO2max?
- No, VO2max is limited by cardiac output (maximal heart rate), not by utilization by muscle tissue
- yes, absolutely
- Nobody knows for sure
but still some doubted
Maximal oxygen consumption (exercise) is related to mitochondrial respiration in elderly (avg. 78 years)![]()
So what?
- No problem, as long as elderly do not exercise to their maximal intensity
- Well, this may also influence their normal physical functioning
- Who needs mitochondria anyway, i only do resistance exercise that doesn't require oxidatice phosphorylation
What happens with capillarization when ageing?
- Lower capillary to fiber ratio in elderly
- associated with VO2 max
capillarization & sarcopenia
- Lower capillary to fiber ratio and capillary-fiber contacts in sarcopenic subjects
Anyone knows what PGC-1alfa is?
- A transcriptional coactivator, involved in the regulation of mitochondrial functioning
- An alfa-subunit of complex IV
- A phosphorus-containing high-energy substrate involved in mitochondrial ATP production
- An Italian brand hybrid passenger car
- A transcriptional coactivator, involved in the regulation of mitochondrial functioning
What is the role of PGC-1alfa in mitochondrial functioning
- PGC-1alfa content is lower in low-functioning than in high-functioning elderly
- PGC-1alfa content is related to cytochrome-c oxidase (complex IV) activity
- Indicating the importance of PGC-1alfa for mitochondrial functioning during human ageing
What is the role of PGC-1alfa in physical functioning?
- Gait (walking) speed is higher in high-functioning than in low-functioning elderly
- PGC-1alfa content is related to gait (walking) speed
- Indicating the importance of PGC-1alfa for physical functioning during human ageing
What is the role of PGC-1alfa in physical functioning?
- Gait (walking) speed is higher in high-functioning than in low-functioning elderly
- PGC-1alfa content is related to gait (walking) speed
- Indicating the importance of PGC-1alfa for physical functioning during human ageing
Thus, the effects of ageing on muscle energetics are less pronounced in physical active subjects. Is this cause or consequence?
- Cause. Those subjects can be so physical active because they have good mitochondria and adequate capillarization
- Consequence. By staying physical active, you will counteract the effects of ageing on your muscle energetics
- You cannot tell from these cross-sectional studies, you need intervention studies
- What is a muscle?
3. You cannot tell from these cross-sectional studies, you need intervention studies
16 weeks of endurance exercise training in sedentary elderly (60-79) increases the following things (4)
- Increase in VO2max: 37±2 to 42±2 ml/min/kg lean body mass
- Increase in mitochondrial volume density
- Increased expression of complex III, IV and V (protein)
- Increased expression of PGC-1alfa and TFAM (mRNA)
Synthesis of cytochrome-c oxidase subunit 4 and NADH subunit 4 in human muscle increases by 66% after 16 weeks of exercise training in all ages
===> adaptive capacity of skeletal muscle persists also at higher age
12 weeks of combined exercise training increases capillary to fiber ratio in older men (74±8yrs)
- in both fiber types (I and II)
How does the in vivo mitochondrial oxidative functioning?
- Skeletal muscle tissue contains immediate energy sources, in particular phosphocreatine (PCr), that are used during the initial phase of exercise
- Post-exercise recovery of PCr --> depending on oxidative metabolic pathway --> reflects mitochondrial oxidative functioning
- Post-exercise recovery of PCrcan be measured directly (31P-MRS) or indirectly (muscle O2 consumption, mVO2 --> NIRS)
In vivo PCr synthesis & ex vivo respiromtery & ageing
- 31P-Magnetic resonance spectroscopy
- Rate of post-exercise restoration of PCr stored (± maximal ATP synthesis rate) in vastus lateralis is related to ex vivo mitochondrial respiration in eldery (avg. 78 yrs)
- Suggesting that the ex vivo results are reflecting the in vivo situation
- At increasing age
- VO2max decreases
- Post-exercise PCr recovery vastus lateralis (31P-MRS)
- VO2max related to PCr recovery vastus lateralis
Not all muscles are equal
The is no difference in post-exercie PCr recovery in calf of young and old subjest
What is further known?
- Mainly vastus lateralis biopsies
- Review of available 31P-MRS studies suggest differences between skeletal mu
scle groups
- Limited evidence from muscle comparisons in the same subjects
- age
- level of physical activity
What is the Near-infrared spectroscopy (NIRS) technique?
- Oxygenated and deoxygenated haemoglobin (+myoblobin) show a different pattern of extinction coefficients in infrared spectrum range
- NIRS device: PortaMon
- 3 transmitters (spatially-resolved spectroscopy)
- 2 wavelengths optimized for oxy-Hb and deoxy-Hb (750 and 850 nm)
- Measuring at different maximal depths (apr. Half the interoptode distance ± 15, 18 and 20 mm)
What happens when looking at NIRS & oxygen utilisation?
- Vascular (arterial and venous) occlusion
- pressure > systolic blood pressure
- NIRS signals:
- Deoxy Hb signal increases
- Oxy Hb signal declines
- Total Hb remains stable
- Slope: O2 utilisation by tissue
What is the NIRS protocol?
- Set of 3 occlusions to measure basal mVO2
- Ischemia - reperfusion protocol to determine
minimal (0%) and maximal (100%) oxygenation levels (Oxy Hb signal)
- Short (ca. 30s) exercise to lower intramuscular PCr stores
- Repetitive (up to 20) short vascular occlusions (5-10 s each)
- using slopes to model post-exercise recovery of mVO2 (rate contact)
NIRS is used for the assessment of mitochondrial capacity.
- m. Gastrocnemius (A) - recovery from plantar flexion
- tibialis anterior (B) - recovery form dorsiflexion
- vastus lateralis (C) - recovery form electrical stimulation
mulste-specific effect of ageing
- lower mitochondria capacity in m. Gastrocnemius and vastus lateralis
- no effect in tibialis anterior
What are the OXPHOS complexes
- Decreased protein expression of CII and CIV (corrected for total protein) in vastus lateralis
- CI and CIV protein expression correlated to mVO2 recovery (NIRS)
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