11/11- Aging of the Muscles and Skeletal System

Question 1

How does muscle change with age?

Answer 1

• Decreased muscle mass relative to body weight
• Also, old muscle is marbled
• Decreased strength
• Huge variability between individuals and muscle groups

Question 2

Describe the decrease in muscle mass with aging

Answer 2

• 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)

Question 3

What are implications of sarcopenia?

Answer 3

• 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

Question 4

Fun facts: young are stronger than mass predicts while old are slightly weaker than mass would predict

• What are some associated changes

Answer 4

• 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

Question 5

Describe decreases in strength with age

Answer 5

• 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

Question 6

How does grip strength change with age?

Answer 6

Grip strength decreases with age

• Opposed from auto worker findings

Question 7

How does lower extremity strength change with age? Elaborate

Answer 7

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

Question 8

How does endurance change with age?

Answer 8

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

Question 9

How does muscle perfusion change with age?

Answer 9

• 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

Question 10

Review: what are the different muscle types?

Answer 10

• Type I: slow (dark, red)
• Type II: fast
• IIa: fast oxidative
• IIb: fast glycolytic
• IIx: fast

Motor nerve unit innervates only one type

Question 11

How does muscle composition change with age?

Answer 11

• 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

Question 12

Describe modifications of muscle composition with age

Answer 12

• 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

Question 13

What changes occur at/proximal to the neuromuscular junction with age?

Answer 13

• 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)

Question 14

How does the number of motor units in EDL change with age?

Answer 14

Decrease

Question 15

What alterations of innervation occur with age?

Answer 15

• 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

Question 16

What was found in transplantation experiments?

Answer 16

• 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

Question 17

Describe energetics and mitochondria changes with age

Answer 17

• 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

Question 18

Describe how contractile proteins change with age

Answer 18

• 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

Question 19

Describe rate of contraction/relaxation in elderly

Answer 19

• Both phases impaired by age
• Time to peak tension is prolonged
• Relaxation time prolonged

Question 20

How do satellite cells change with age?

Answer 20

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

Question 21

Describe the old muscle in injury

Answer 21

• 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

Question 22

Describe the parabiosis experiments and results?

Answer 22

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

Question 23

Describe how inactivity contributes to the changes seen with aging

Answer 23

• 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

Question 24

What may be a good mirror of your true age

Answer 24

Muscle may be the mirror of someone’s aging process

Question 25

How do anabolic hormones change with age?

Answer 25

• 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!!

Question 26

Describe how resistance training affected strength in little old ladies

Answer 26

• 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)

Question 27

What are aging changes in joints and cartilage?

Answer 27

• 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)

Question 28

How does bone change with aging?

Answer 28

• 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

Question 29

What are some of the factors that play a role in bone loss?

Answer 29

• Conditioning and exercise
• Nutrition
• Vascular and neurologic abnormalities
• Inflammaging and other pro-inflammatory states

Question 30

How do hormone changes affect bone loss?

Answer 30

• Growth hormone and IGF-1 decrease
• Estrogens decrease
• Androgens decrase

Question 31

What are ethnic differences in bone mass?

Answer 31

• 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)

Question 32

Summary

Answer 32

• 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