sarcopenia / generalised muscle wasting

see also:

• weakness of the lower limb(s) / weak in the knees
• motor neurone disease (MND)
• exercise for health

• sarcopenia is a very common problem with aging and is a leading cause of frailty
• it is characterized by progressive and generalized loss of skeletal muscle mass and strength
• it has high correlations with physical disability, poor quality of life and death
• presarcopenia stage is characterized by low muscle mass without impact on muscle strength or physical performance
• loss in muscle mass may be associated with increased body fat so that despite normal weight there is marked weakness, this is a condition called sarcopenic obesity.
• sarcopenia is different to cachexia which may be defined as a multifactorial syndrome characterized by severe body weight, fat and muscle loss and increased protein catabolism due to underlying disease

• pronounced changes in muscle tissue begin from around 50 years of age
  • muscle mass and strength begin to deteriorate at an annual rate of 1–2% and 1.5–5% respectively
• up to 10% of 60-69 yr olds have sarcopenia
• 40% for adults over 80 years of age

• primarily a syndrome of old age
• risk factors include:
  • age
  • gender
  • low level of physical activity
  • protein malnutrition
  • sleep quality
  • alcohol intake
  • smoking status
  • chronic inflammatory conditions
  • genetic factors:
    • genetic factors account for 46–76% and 32–67% of fat-free mass (FFM) and muscle strength variability, respectively and thus far it seems 24 genes and 46 DNA polymorphisms whose expression is significantly associated with muscle phenotypes in older adults have been found ¹⁾
    • ACTN3 (the “sprint gene”):
      • 1 in 5 people have genetic α-actinin-3 deficiency due to homozygosity for the premature stop codon at the rs1815739 (R577X) polymorphism which is associated with significantly lower strength and higher frailty scores as they age²⁾
        • a meta-analysis using two large independent cohorts of Caucasian postmenopausal women showed that even heterozygous carriage of the ACTN3 577X allele increases the risk of falling by 33%³⁾
    • VDR polymorphisms
    • IGF1 and IGFBP3
    • CNTF and CNTFR
    • TNFα
    • ACE rs1799752 (insertion/deletion) polymorphism
    • Apolipoprotein E (APOE) gene
    • Uncoupling Proteins 2/3 (UCP2/3) polymorphisms
    • PR domain containing 16 (PRDM16) gene
    • Zinc finger protein 295 (ZNF295) gene
    • C2 calcium dependent domain containing 2 (C2CD2) gene

• Creatinine Muscle Index (CMI)
  • CMI (mg/day) is calculated as eGFR cystatin C × serum creatinine concentration
  • Creatinine is a marker of kidney function, but is metabolised in muscle and thus its levels also relate to amount of muscle mass.
  • Cystatin C is a measure of kidney function that is independent of muscle mass.
  • 2026 study⁴⁾ showed it was independently associated with muscle function and mortality, supporting its utility in populations with reduced kidney function.
    • lower CMI (indicating lower muscle mass) was linked to weaker hand grip strength, slower walking speed, and a higher risk of sarcopenia
    • higher CMI was also linked to a lower risk of death. For every 100 mg/day per 1.73 m2 increase in CMI, the risk of death fell by 15% in men and 23% in women.

• adequate protein intake
• muscle resistance training combined and possibly creatine supplements appear to build muscle mass more effectively than resistance training alone and may add an extra 1.4kg mass compared to no creatine supplementation ⁵⁾
  • estimated daily requirement of creatine is about 2 g/day for a 70-kg male however endogenous synthesis of creatine may be inadequate under pathological or certain physiological conditions
  • creatine-rich foods include fish and meat
  • supplementation protocols, such as an initial loading phase of 20 g/day for 5–7 days followed by a maintenance dose of 3–5 g/day, have shown consistent benefits in enhancing muscle performance and lean mass.
  • exercise programs should include progressive weight training, with up to 10 exercises targeting major muscle groups and 8–12 repetitions per exercise.
  • both high- and low-frequency resistance training can effectively improve skeletal muscle mass, muscle strength, and quality in older females with sarcopenia
• leucine supplements
  • leucine, in combination with resistance training, has been found to improve muscle function and reduce muscle loss in elderly patients with sarcopenia. Due to age-related anabolic resistance, older people require approximately twice as much dietary leucine as young adults to achieve similar increases in muscle protein synthesis⁶⁾
• β-hydroxy-β-methylbutyrate
  • β-hydroxy-β-methylbutyrate is a leucine metabolite that the International Society of Sports Medicine has endorsed as a safe dietary supplement across various populations, including athletes, non-exercising and sedentary individuals, and patients with sarcopenia. Recent evidence supports its effectiveness in enhancing muscle protein synthesis, reducing protein breakdown, and improving muscle strength and function. Real-world benefits still require confirmation through larger, long-term studies. ⁷⁾
• magnesium
  • magnesium supplements in healthy elderly women have been found to improve physical performance and conserve skeletal muscle mass and strength. Magnesium supplements can significantly increase the abundance of beneficial bacteria in the gut ⁸⁾