Sarcopenia: age-related declines in skeletal muscle Flashcards
-Background to muscle mass maintenance: o Describe why muscle is important o Explain how muscle mass is regulated in healthy individuals and how we can measure this -Apply to sarcopenia: o Describe sarcopenia and its clinical manifestations o Discuss the molecular and metabolic alterations that underpin sarcopenia o Consider how what we know from molecular studies inform interventional approaches -Emphasis on main stimuli of muscle growth: o Exercise o Nutrients
Why is muscle important?
o Skeletal muscle is specially designed to contract
Generates mechanical force
Muscle mass correlates strongly with force production and overall function
o Bodies largest mobilisable source of amino acids in times of organismal need
o Largest site of glucose uptake
o Contributes to approx. 25% basal energy expenditure
o Releases signals (‘myokines’)
o Serves as a metabolic buffer
o Temperature regulation
o Muscle mass and strength are strong predictors of all cause mortality and morbidity
How is muscle mass regulated?
o Muscle mass is ultimately regulated by dynamic protein turnover
o Protein turnover = balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB)
Myofibrillar proteins (contractile apparatus)
Sarcoplasmic proteins
Mitochondrial proteins
Collagen proteins
Net muscle protein balance = MPS minus MPB
o Over a day (without resistance exercise), MPS is same as MPB = No change in muscle mass
o So, changes in muscle mass occur due to dynamic changes in protein synthesis and breakdown, which are caused by changes in molecular signalling activity
But how do we measure changes in molecular signalling activity?
o A-V Tracer Exchange Model for Macromolecule Turnover
o Tracer enters circulation, reaches muscle, is used when making new protein, then measured in blood and muscle
o Requires collection of muscle biopsies to measure incorporation into muscle proteins
What are the most potent stimulators of muscle growth?
o Nutrients + Contractile activity
In the rested, fasted state net protein balance is negative (breakdown > synthesis)
What does growth and wasting do to protein turnover?
Protein synthesis is facilitative, protein breakdown is adaptive; I.e. most changes occur due to alterations in S and B follows to lessen the effects - except for fast wasting.
Disorganised myofibres (?)
o Aged Caenorhabditis elegans (worms) with myofibres tagged with green fluorescent protein
o Functional effect would = impaired mobility
Why does strength decline exceed muscle mass losses during ageing?
o Fat- / collagen infiltration?
o Neuronal decline?
o Impaired E-C coupling?
o Decreased actin-myosin cross-bridge stability?
o Reduced muscle attachment complex stability?
Mechanisms underpinning sarcopenia / dynapenia (?)
o Genetic influence o Immobility o Endocrine factors o Muscle fibre atrophy o Neurodegenerative process o Decreased protein synthesis o Nutritional status
Role of integrin-attachments in sarcopenia?
o Impaired mechanotransduction with age?
o Altered intracellular biochemical response to exercise
o Reduced protein synthetic response to (e.g.) daily activity?
o Poor regenerative capacity?
o Accumulation of muscle ‘damage’?
But what about the response of aged muscle to anabolic stimuli?
o Decreased response of MPS / MPB to food could underlie sarcopaenia
Do older people just not eat enough?
May be influential
Is sarcopenia simply a result of disuse atrophy?
o May contribute, e.g.:
Bed rest induces atrophy via depressed MPS and (to a lesser extent) increased MPB
Spaceflight induces atrophy, primarily via depressed capacity for MPS
Eccentric training – helpful or harmful?
o Eccentric strength remarkably well preserved in ageing – Zembron-Lacny et al. (2014). Physiol Res, Epub ahead of print.
o Optimal approach to initiate RE training in elderly?
o Eccentric training also maximises strength gains vs. concentric training in young healthy people
o CON increases pennation angle; ECC increases fascicle length in young (Franchi et al. 2014) and old muscle (unpublished)
o May increase muscle power but not strength / hypertrophy – Vaczi et al. (2014). Exp Gerontol, 58: 69-77.
o However, aging muscle likely exhibits impaired regenerative capacity – Role for impaired mechanotransduction?
o Thus, accumulation of unrepaired muscle ‘damage’ after eccentric bouts may actually make elderly muscle worse
o Would expedite the progression of sarcopaenia
Prevalence of and Interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (Landi et al., 2014)
Prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.
