11/11- Aging of the Muscles and Skeletal System Flashcards
1
Q
How does muscle change with age?
A
- Decreased muscle mass relative to body weight
- Also, old muscle is marbled
- Decreased strength
- Huge variability between individuals and muscle groups
2
Q
Describe the decrease in muscle mass with aging
A
- 30-40% decrease in muscle mass from age 30 - 80
- Not linear, loss accelerates with age
- “Sarcopenia”: muscle loss makes up most of the loss of lean body mass seen with aging
- Creatinine production (primarily produced by muscle) decreases by about 50% from 25-90
(although no rise in serum values since kidney function also drops)
3
Q
What are implications of sarcopenia?
A
- Implicated in decreased performance and increased falls - Loss of reserves so bedrest may become permanent
- DON’T do super conservative orthopedic surgery if it means they can’t be up and about soon
- Contributes to:
- Insulin resistance
- Cold intolerance
4
Q
Fun facts: young are stronger than mass predicts while old are slightly weaker than mass would predict
- What are some associated changes
A
- Increased intramuscular fat with age
- Non-contractile tissue is 8% of CSA at age 40 but 18% at age 70
- Old muscle injured more easily
5
Q
Describe decreases in strength with age
A
- From age 20-70 strength decreases 50% in legs
- Non-linear decline
- Accelerates with increasing age
- 30% decrease in strength from 50-70
- 80 yo are 30% weaker at knee extensor than 70
- Loss of strength is smaller when corrected for loss in muscle mass
- Decrease is same in men and women!
- 40% decrease in strength overall (average of arms and legs), wide variation between muscle groups
- Upper body strength decreases LESS rapidly than leg
- Important role of activity here in that workers that consistently use a given muscle have no decrement in strength with age
6
Q
How does grip strength change with age?
A
Grip strength decreases with age
- Opposed from auto worker findings
7
Q
How does lower extremity strength change with age? Elaborate
A
Lower extremity strength decreases with age
- Dramatic falls in max torque generated by knee extensors seen in both men and women
- Presence of heart disease had minimal impact compared to age
8
Q
How does endurance change with age?
A
Decreased endurance in old
- Older people fatigue faster than young
- Remaining muscle works at a lower percentage of max function
- Decreased number of capillaries per motor unit
- Decreased max blood flow
Weird, because those who exert strong enough to shut off blood flow, will have less endurance; those who don’t might actually have better endurance
9
Q
How does muscle perfusion change with age?
A
- Modest decrease in blood flow at rest
- Important decreases in max flow
- Max oxygen extraction decreases with age
- This is modifiable by exercise!
- Muscle capillary density unchanged with age
10
Q
Review: what are the different muscle types?
A
- Type I: slow (dark, red)
- Type II: fast
- IIa: fast oxidative
- IIb: fast glycolytic
- IIx: fast
Motor nerve unit innervates only one type
11
Q
How does muscle composition change with age?
A
- Preferential loss of type II fast fibers (esp type IIb)
- Type I fibers also decrease
- Still, relative enrichment of type I
- Loss of strength correlates strongly with decrease in type II fibers
- Controversy exists as to the extent of this…
- Nerve changes can prompt switch from II to I as precursor to fallout
- Loss of total number of fibers and decrease in CSA of each fiber, esp type II
12
Q
Describe modifications of muscle composition with age
A
- Increased lipofuscin deposition (brown granules)
- Reduced size of myofibrils
- The loss in cross-sectional area of each myofibril is greater than loss in number of myofibrils
- Reduced number of myofibrils
- Increased CT and fat
13
Q
What changes occur at/proximal to the neuromuscular junction with age?
A
- The number of motor units decrease by 50% with age
- Similar to relative denervation
- Loss of alpha motor neurons and re-innervation by remaining neighbor neurons
- Results in inefficient large motor units
- Mass of muscle is preserved (relatively to cutting nerve/atrophy)
- Strength of muscle declines (in part because of stimulation failure)
- In isolated nerve-muscle preparations, tension developed by old muscle is relatively well preserved after nerve stimulation (electric shock stimulation allowed improvement compared to own nerve stimulus)
- Nerve is crapping out (why elderly are weaker than muscle mass)
14
Q
How does the number of motor units in EDL change with age?
A
Decrease
15
Q
What alterations of innervation occur with age?
A
- Decreased number of motor units
- Motor units enlarge to compensate for loss of innervation
- New synapses are unstable
- Many motor neurons have huge arbors
- Failure of synaptic transmission more frequent
- Up to 25% of motor units essentially non-functional
- Muscle fibers not denervated but hypo-innervated
- Nerves can provide trophic factors to keep muscle viable and determine muscle type
- Impact much more important after age 70
16
Q
What was found in transplantation experiments?
A
- Transplant EDL from 24 m to 4 m rat
- Grafted muscle functional just as well as 4m to 4m graft
- Transplant EDL from 4 m to 24 m rat:
- Poor function
- Poor regeneration
- One key is axonal regeneration for nerve that will innervate graft
- Much of age-related decline is in the nerve, not intrinsic to muscle
- Replacement of denervated muscle with fat
17
Q
Describe energetics and mitochondria changes with age
A
- Marked decrease in old muscle ability to maintain energy balance during contraction
- Impaired return to energy balance after prolonged contraction
- Decreased aerobic potential, oxidative capacity
- Decrease mitochondrial mass and mitochondrial concentration per g muscle
- Non invasive study with NR show impaired creatinine phosphate resynthesis
- Anaerobic metabolism unchanged
18
Q
Describe how contractile proteins change with age
A
- Decreased rates of synthesis and degradation with aging
- Old rats have decreased mRNA for alpha-sk actin, normal for beta-myosin heavy chain
- Similar dis-coordination seen after unloading
- Short term studies unenlightening relevant to long term cahnges
19
Q
Describe rate of contraction/relaxation in elderly
A
- Both phases impaired by age
- Time to peak tension is prolonged
- Relaxation time prolonged
20
Q
How do satellite cells change with age?
A
Recall: satellite cells are the key to repair, growth, and remodeling of muscle
- Cannot regrow after muscle after forced inactivity
- Deficits in repair are apparent early in life
- Limited proliferative potential has implications for cell-based gene therapy of muscular diseases
- Dedifferentation to adipocytes with age
- Uncertain role of blood-derived cells
21
Q
Describe the old muscle in injury
A
- Much slower recovery after damage
- Decrease in pluripotential satellite cells
- Old satellite cells produce much smaller colony size in vitro
- After 6 wks in a cast:
- Young people will return to precast strength and mass
- Old people never return to precast levels
22
Q
Describe the parabiosis experiments and results?
A
Parabiosis experiments involved sewing young/old rats together
- Young environment improves muscle repair
- Suggests that there are circulating factors in the young animal (including progenitor cells) that can integrate into the old animal and allow cells to repair
23
Q
Describe how inactivity contributes to the changes seen with aging
A
- Diaphragm relatively resistant to aging changes
- Evidence that some of the “aging” effect is due to inactivity
- Auto workers that continuously use muscles have no decrement in strength
24
Q
What may be a good mirror of your true age
A
Muscle may be the mirror of someone’s aging process
25
Q
How do anabolic hormones change with age?
A
- Normal aged humans are GH deficient
- Anabolic response to exogenous IGF-1 is unaltered by age
- His observation is that IGF-1 is transgenic mice have age-related muscle atrophy just like wild type
- Anabolic steroid response is also unaltered by age and may have role as therapeutic agent
- Vitamin D is the forgotten anabolic hormone; if it is low, replace it!!
26
Q
Describe how resistance training affected strength in little old ladies
A
- Weight training of very old ladies resulted in 145% increase in strength!
- Muscle mass increase was less than 10% (in young person, there would be HUGE hypertrophy)
27
Q
What are aging changes in joints and cartilage?
A
- Water content of articular cartilage decreases with age
- Ability of cartilage to withstand the compressive load depends on ability to expel and imbibe water
- Proteoglycan monomer content and size are decreased
- Proteoglcyan aggregates fragmented
- Chondroitin sulfate chains decreased modestly
- increased keratin sulfate and hyaluronic acid (perhaps compensatory)
- Surface depression depth increases (less re-imbibing of water)
- More crosslinking of long-lived proteins
- Age changes do not mean osteoarthritis (but may make it worse)
28
Q
How does bone change with aging?
A
- Bone loss is universal aspect of aging
- Loss is more rapid in women than men, especially after menopause (type I)
- Haversian system growth slows
- Cortex thins and becomes more porous - Subperiosteal deposition is slower than endosteal erosion
- Trabecular lattice loses horizontal support and strength
- Increased likelihood of collapse
- There is a different patter of bone loss between genders
- Peak bone mass is less in women than men
- Menopausal bone mass is sharp decline in women
- Bone loss with age occurs in both
- Osteoblast activity is greatly reduced
- Osteoclast activity is less altered
- Removal faster than deposition
- Healing of fractures much slower in old
- Bone marrow precursors of osteoblasts decreased
- Skull thickens with age
- Multiple changes in Vitamin D metabolism
- GI Ca absorption decreases with age
29
Q
What are some of the factors that play a role in bone loss?
A
- Conditioning and exercise
- Nutrition
- Vascular and neurologic abnormalities
- Inflammaging and other pro-inflammatory states
30
Q
How do hormone changes affect bone loss?
A
- Growth hormone and IGF-1 decrease
- Estrogens decrease
- Androgens decrase
31
Q
What are ethnic differences in bone mass?
A
- African Americans have more skeletal mass at any age
- Lower frequency of hip fractures in both black men and women
- Aged blacks in US have 2x the risk of Africans in Africa (so part of it is environmental)
32
Q
Summary
A
- Skeletal muscle decreases in mass, strength, and quality with aging
- Part of the decreases are due to changes at the neuro-muscular interface
- Resistance exercise can modify performance such that old people get much stronger
- Old joints work less well, but age does not equal osteoarthritis
- Bone loss is also an age-related phenomenon in men and women
