Physical performance level in sarcomeric mitochondria creatine kinase knockout mouse model throughout ageing.

Area of Science:

• Exercise physiology
• Mitochondrial biology
• Aging research

Background:

• Mitochondrial creatine kinase (Mt-CK) plays a crucial role in cellular energy buffering, particularly in muscle.
• Understanding Mt-CK's role in aging is vital for comprehending age-related decline in muscle function.
• Mt-CK deficient mice (Mt-CK-/-) provide a model to study these effects.

Purpose of the Study:

• To investigate the role of sarcomeric mitochondrial creatine kinase (Mt-CK) in muscle energy output during exercise.
• To assess the impact of Mt-CK deficiency on exercise performance and physiological adaptations in aging mice.

Main Methods:

• Utilized Mt-CK knockout (Mt-CK-/-) and control mice across three age groups (6, 9, 18 months).
• Performed incremental treadmill running tests to measure maximal speed (Vpeak) and maximal oxygen consumption (VO2peak).
• Analyzed urine metabolomics and quantified key mitochondrial biogenesis proteins (PGC-1α, Mnf2) in skeletal muscle.

Main Results:

• 18-month-old Mt-CK-/- mice exhibited significantly lower VO2peak and Vpeak compared to younger counterparts and controls.
• Skeletal muscle mass was reduced in young Mt-CK-/- mice, with urinary branched-chain amino acids suggesting altered protein turnover.
• Age-related effects on PGC-1α and Mnf2 expression were more pronounced than genotype-specific effects.

Conclusions:

• Mt-CK deficiency potentiates aging-related decline in exercise capacity (VO2peak, Vpeak) and mitochondrial protein expression.
• Mt-CK-/- mice develop compensatory physiological adaptations to maintain performance, potentially at a high energy cost.
• These adaptations may contribute to a premature aging phenotype in Mt-CK deficient mice.