Ageing and skeletal muscle Flashcards
Compare lifespan and healthspan
- Lifespan - how long you are alive for - life expectancy
- Healthspan- how long are you healthy for
What are pro-aging factors?
- Loss of renewal capacity:
- Stem cells
- Telomeres
- Hormornal changes
- Accumulation of Damage
What are Longevity Assurance Systems?
- DNA repair
- Stress responses
-Antioxidant defenses - Protein and cell turnover
- Mitochondrial Maintainenace
What is genome analysis?
- Looking into 1000s of hemes
- Single nucleotide polymorphisms (SNPS)
- We can look at complex genetic signatures
- Very few genes consistently involved
- No genes associated with diseases
- Genes do not solely governn whether you will live longer than an average lifespan
What is the concept of hormesis?
- Something that causes harm but up to a certain point, that harm may be beneficial/ have a positive benefit e.g.g exercise
What are the changes in muscle mass with aging?
- 40% loss in muscle mass from 20-70 years of age
- 6% decline in muscle mass per decade from aeg 30-70
1.4-2.5 % decline in muscle mass per year after 60 - 6% decrease in leg muscle volume over a 5 year follow up - from 71-76 years olf
What is sarcopenia?
- Age-associated decline in muscle mass
Sarco = flesh, penia = deficiency - Asssociated with increased mortality and functional decline
What is the prevalence of sarcopenia?
- More prevalent in females (60-75)
- <70 -85 increase in sarcopenia in men
What is the catabolic crisis model?
Muscle catabolism leads to a loss of muscle mass. This process reduces muscle protein levels, which are essential for building and repairing muscle. The reduction in muscle mass has a negative impact on body appearance and the body’s ability to process fat and carbohydrates
- e.g. injury and bed ridden = loss of muscle , never gained back
What is sarcopenia?
- Sarcopenia = reduced musclemass, also associated with decreased muscle quality
What are some cross -sectional studies for ageing muscle?
- Fibre loss - denervation , apoptosis
- Fibre atrophy
- Ratio of type II/I goes from ~ 1.25/1 to ~0.85/1 between ages 30-80
- Lower extremities> Upper extremities
- Postural/locomotor> non-postural
- Rate of loss in males > females
What can cause sarcopenia (satellite cells) ?
- Satellite cells - central to muscle regeneration/maintainenance
- SC content decreases with age
- Loss of SCs is specific to type II muscle fibres
- Currently all associative : no evidence yet that SC decline preceds sarcopaenia
What is motor unit remodelling?
- Loss of normal innervation
- Denervation and reinveration
- Loss of motor neuron leaves fibres denervated
- Denervation causes motor neuron loss
What are the changes in muscle metabolism with age?
- Increase in mitochondrial DNA mutation
- Decline in muscle mitochondrial protein synthesis (40%)
- Decreased oxidative phosphorylation and ATP generation
- Results in fatigability
- Decline in myosin heavy chain synthesis
- Major protein involved in ATP and conversion of chemical to mechanical energy
What is mitochondrial dysfunction?
- Disrupted mitochondria also display abnormal function in humans
- Lowered mitochondrial :
- Content (overall capacity)#
- Oxidative capacityy per mitochondrial volume
- Mitochondrial protein concentration
- Mitochondrial ATP production (MAPR)
What are the effects of ageing on muscle protein turnover?
- Postabsorptove (fasting) protein balance is unchanged in the basal state in elderly
- Acuumulation of neg effects of ageing cells may decrease muscle quality/function when protein balance is unchanged
What are the effects of healthy aging on dose response of MPS to EAA?
- Accumulation of small but meaningful decreases = leads to atrophy
= ANABOLIC - Muscle protein breakdown also not suppressed after feeding in the elderly
MPS- Muscle Protein Synthesis
EAA - Essential Amino Acids (Stimulator of MPS)
FSR - Fractional synthetic rate (i.e. rate of newly made protein)
Explain glucose metabolism in older muscle
- Older muscle does not swithch to glucose metabolism in response to insulin
- suggests that muscle is less able to dispose of glucose with age and therfore contributes to age related diabetes.
What is dynapaenia?
- Porgressive loss of muscle function during the ageing process
- In elderly people, functional capacity is directly dependent on muscle size/ fitness
- 65-80 yr have approc 20-40 % decline in leg maximal voluntary force production
(MVC) - 50% decline in MVC with progressive age
What is muscle strength?
The maximum capacity to generate force or tension declines
What is strength loss in ageing (percentages)?
- Strength increases up to age 30
- Plateaus from age 30-50
- Declines 24-36% betweem 50-70
- 12% decrease in leg muscle strength over a 5 year follow up from 71-76 years old
- Most precipitous loss after 70
- 15% loss per decade up to 6th and 7th decades of life
- 30% loss per dcecade thereafter
- 35% loss over 11 year period in 80 year old subjects
- Women unable to lift 4.5 kg (!0 ibs) increased from 40% in 55-64 year olds to 65% in those afe 75-84
Why does the max capacity to henerate force or tension decline?
- Mucsle Cross sectional area
- MU recruitment/ Firing rate
- Intrinsic factors
What are mean motor unit forces?
- Fast fatigable FF motor units get smaller in old age and decrease in number
- Slow twitchs motor units get bigger with no change in number
- Decreased rate of force generation and POWER
Explain what happens with SKM quality with age
- More fat infiltration of muscles
- Increased fibrosis/ disorganised extracellular matrix
What mechanisms underpin sarcopenia / dynapenia?
- Genetic influence
- Immobility
- Muscle fibre atrophy
- Neurodegenerative processes
- Decreased protein synrhesis
- Nutritional status ( decreased protein and energy intake)
- Autophagy, Apoptosis, Mitochondria dysfunction
- Endocrine factors (decreased GH, IGF-1, sex steroids, insulin resistance)
