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Ageing Systems > Skeletal muscle ageing > Flashcards

Skeletal muscle ageing Flashcards

1
Q

rate of strength loss for men & women annually?

A

3.5 and 2.7 %

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2
Q

rate of mass loss for men & women annually?

A

0.47 and 0.37 %

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3
Q

what contributes to osteosarcopenic obesity

A

osteopenic obesity and sarcopenic obesity

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4
Q

what does osteosarcopenic obesity, increase the risk of?

A

fractures / morbidity - while decreasing functionality

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5
Q

what are the effects of loss of lean mass of 10 / 20 / 30 / 40 %

A
  • deceased immunity and increased risk of infection
  • decreased wound healing and increased muscle weakness
  • pressure ulcers and pneumonia
  • increased risk of death usually from pneumonia
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6
Q

what is the AA glutamine’s main function

A

to support the repair process and maintain the immune system

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7
Q

what are the four main things derived from ageing muscle

A
  • metabolic dysfunction
  • loss of mass
  • loss of function
    mitochondrial dysfunction

all contributing to reduced quality of life

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8
Q

why do muscles have lipid droplets deposited near mitochondria

A

to provide fast energy - can be observed under a minor array or electron microscope.

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9
Q

what are free AA

A
  • protein repletion for growth
  • oxidation ( eg excretion of urea)
  • transformation ( eg gluconeogenesis)
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10
Q

how can carbon skeletons of amino acids be used as fuel

A

KETOGENESIS - removal of alpha amino acid group. leaving the skeleton to be used as a metabolic intermediate or GLUCONEOGENESIS, forming glycogen for storage.

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11
Q

what does carbohydrate metabolism provide

A

storage of glycogen and conversion of glucose

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12
Q

how are glycogen stores depleted

A

fasting and exercising

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13
Q

how much glycogen can the liver store

A

100g

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14
Q

what is the max glycogen storage of the body

A

3-500g

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15
Q

what are satellite cells

A

essentially muscle stem cels and they become less responsive to to repair leading to reduced regenerative capacity as they age

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16
Q

what is mitochondrial dysfunction free radical theory

A

Mitochondria generate atp and ros, which become scavenged in healthy muscle

  • Overfeeding with reduced energy demand leads to metabolic stress and increased ros production – production is close to DNA and therefore leading to genetic lesions
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17
Q

what does inflammation in ageing muscle cause

A

stimulates the release of catabolic cytokines such as TNF alpha and IL - 6. also activating mitochondria leading to increased production of R.O.S

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18
Q

What are stable isotopes

A

naturally occurring and contain extra neutrons. Safe for use in humans as well as being biologically relavant

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19
Q

advantages of STABLE isotopes

A
  • Heavy elelments can be encorporated into any compound via chemical or enyme reaction
  • Behave like endogenous compounds and can trace things such as metabolism
  • Differentiated form endogenous using mass spectrometry
  • Allow recording of dynamic measurments such as rates instead of static like concentration
  • Non radioactive
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20
Q

applications of STABLE isotopes

A
    • Arterio venous balance mechanisms, sampling of blood flow of labelled compounds to assess net uptake / release and intermediatory metabolism of labelled compounds
    • Allows evaluation of dynamic proteonomics (turnover of muscle proteins and plasma) and metabolics.
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21
Q

negatives of STABLE

A
  • Constant iv requires study in a lab over 24 hours, however typically less than 8
22
Q

What are the advantages of D20

A
  • Taken orally as one bolus or as regular doses
  • It rapidly equilibriates with the bodys water, ending the need for iv infusions.
  • Can calculate and experiment multiple rates at once.
  • Relatively slow turn over of bodys water pool, promotes measures over long times
23
Q

ageing effects on insulin

A

decreased insulin sensitivity, insulin required for inhibition of proteolysis

24
Q

how does obesity and inflammation effect protein turnover

A
  • decreased insulin sensitivity, increased proteolysis
  • lower glucose disposal
  • blunted mps
25
Q

elderly show increased central fat storage - even with reduced energy expenditure and overall activity

A

fatty acid oxidation is also reduced leadings to storage of fats in muscles centrally

26
Q

how do the elderly show metabolic blunting

A
  • reduced anabolic responses from essential AA and protein
  • reduced insulin sensitivity, a potent anabolic hormone
  • anabolic response to exercise alone is also reduced
  • reduced glucose uptake and oxidation
27
Q

how to combat metabolic blunting in the elderly

A
  • increase protein consumption
  • timing of meals around training
  • increased training volume
  • hormone supplementation ( IGF-1 / GH/ T4)
28
Q

standard interventions to reduce muscle loss in ageing

A

Exercise – increasd function by increased vol of exercises and increased insulin sensitivty by increased lipid metabolism with acitivty

Nutrition – sufficient protein feeding / leucine supplementation / hmb (from leucine) to supplement mps

Pharmaceutical – t4 or sarms

29
Q

Elderly populations show strength loss 2.5 x faster than mass loss, leading to …

A

compramsised muscle functions and increased hospitalisations, disability and even deaths

30
Q

Jan jenson suggested classification of severity (SMI) skeletal muscle index

A

Smi = total muscle mass / total body mass

  • Normal within 1 sd
  • Class 1 sarcopeniac = smi between 1 and 2 sd below normal
  • Class 2 sarcopeniac = smi greater than 2 sd below normal
31
Q

points against sarcopenia

A

as sarcopenia may imply proportional loss of muscle strength to muscle bulk – with ageing muscle showing a greater decline in strength as apposed to muscle (2.5x greater)

32
Q

how is muscle mass normally accessed and why is it done this way

A

dexa scan is used over ct as it’s a fraction of the cost and gives less exposure to potentially harming ionising radiation

33
Q

studdies by - Lanssen, borken and Gallagher showed …

A

Muscle loss is not seen in a uniform way across the body with lower limbs showing greater loss than that of upper limbs – 2x.

34
Q

why do males experience greater loss of muscle with age even after considerations of height and weight

A

asscociated with increased decline of T4. with women showing signs of menopause - loss of testosterone a precursor for oestrogen.

35
Q

muscle function studies on reduced hand grip strength have shown

A
  • Increased hospitlisations with lower scores

- Good example of a inexpeisnve and accessible clinical practice

36
Q

why do elderly show preservation of eccentric strength - in some studies

A

accumulation of non contractile tissue in muscle giving increased passive stiffness and changing the contractile poroperties of the muscle fibres. (fat and lipid droplets deposition)

37
Q

elderly changes in muscle architecture

A

Elderly show a shorter fascicle length – potential contributer towards reduced shortening velocity and force generation

viewed via ultrasound

38
Q

fibre morphology changes

A

Decreased in csa of muscle bulk

No preffernetial loss of fibre type, however in men more type 2 diamter loss is seen (sexual dimorphism)

39
Q

change in my-nuclei density

A

little change in size but the clustering of MND in the grooves of periphery fibres is reduced - potentially implicating the efficiency of mps.

change in mnd:satelite leads to a reduced regenerative function

40
Q

Elderly changes in fibre type biochemistry

A

Can express a mixed form of myhc isofroms – I and IIa for example – givng a mix of contractile properties.
Even some cases all three isoforms

Observed clustered fibre types, suggest denervation or incomplete reinnervation with loss of fast twitch alpha motor units being reinnervated by neighboring slow twitch motor units.
- However this is not seen in smaller more proximal muscles.

41
Q

how is elderly vasoconstriction compromised

A

decreased capillary density is known to happen in sedentary individuals - leading to potential decrease in bulk flow upon exercise.
with reduced density may be from shorter fibres, requiring reduced vasomotor response.

42
Q

signs of compromised vasomotor response

A

hypoxia
free radical stress
compromised nutrient delivery

43
Q

aerobic exercise as a sarcopenic intervention

A
  • triggering mps by expression of mps genes and inhibiting mpb genes
  • shown in older athletes who show protection against age related loss of motor recruitment
  • similar studies have shown nueroportective benefits to be limited to the lower limbs.
  • also shown to help protect against the blunting of insulin
44
Q

where are the majority of non essential AA requested

A

sphlanic tissue = such as alanine in the liver for gluconeogenesis

45
Q

are many essential AA taken up into sphlanic tissue

A

only a small %, allowing miantainance of proteostasis in skeletal muscle.

46
Q

where are branched chain essential AA such as leucine and isoleucine broken down

A

in the muscle

47
Q

explain the muscle ‘fed state”

A

after feeding an initial 45-90 min lag is seen before mps peaks at around 1.5-2 hours. to which after it returns to post abosbative rates. despite substrate availability and anabolic signalling.

48
Q

what are essential AA sensed by

A

motor 1 and rag dependent signalling. elderly showing a poor proportionality between mps and mtorc1.

49
Q

what do satellite cells do

A

provide nuclei to existing myofibrils enabling maintained transcriptional capacity aswel as endogenous satellite cell production.

with each nucleus only managing a certain cell volume of cytoplasm and with hypertrophy as the muscle grows, the uncle content becomes diluted to the point where new source of nuclei is needed to overcome the ‘ceiling effect’

50
Q

what does biological variation for high responders show

A

posses high numbers of satellite cells and greater myonuclei numbers following restrictive training.

51
Q

other age related blunting factors of mps

A
  • attenuated decline in mob in elderly postpradinal
  • depressions in mtorc1 activation in elderly / anabolic signalling may not be as well sensed in elderly, potentially increased with leucine with meals as its a potent anabolic signalling protein.
  • shift in sensitivity (more exercise stimulus needed and demand for volume for reponse)
  • digestion rate, impairing the level of free AA available for mps

Ageing Systems (9 decks)

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