Physiology of Aging Muscle and Connective Tissue

1. Physiology of Aging Muscle and Connective Tissue Jessie VanSwearingen, PhD, PT Associate Professor Department of Physical Therapy University of Pittsburgh School of Health and Rehabilitation Sciences

2. Muscle Physiology: Force Production Motor unit: motor neuron, motor axon, and all of the muscle fibers innervated by the motor axon Motor Unit Recruitment - to Increase Force: - increase the number of active motor units - increase the firing rate of active motor units (Henneman’s Size Principle: recruit small before large)

3. Body Composition Changes and Muscle Mass • 60% of body K+ ; highest ratio of nitrogen by tracing these ions, determined the protein loss in aging is largely skeletal muscle protein loss (Cohn et al, 1980) • evidence suggests decrease in muscle mass • with aging accounts for: • decrease in BMR • decrease in VO2 max • (BLSA, Tzankoff and Norris, 1978)

4. Muscle Function : Force Producing Capacity • decreased muscle force production • begins about 45 years of age • more rapid > 70 years; 25-30% decrease • usually lower extremities > upper extremities • decrease muscle force > decline in cross sectional area(adductor pollicis, ankle plantar- and dorsi- flexors) • Frontera et al (1991), corrected for muscle mass: no difference in MVF / CSA for old • versus young (knee flexors)

5. Muscle Function : Force Producing Capacity • cadaver studies: cross sections of entire vastus lateralis decrease of 10% in CSA, between 30-50 years 25-30% decrease in CSA between 50-80 years (Lexall et al, 1988) • CONCLUDE: • maximal force / unit area remains constant • MESSAGE: • suggests the “quality” of the muscle – intrinsically muscle fibers are able to produce • force in old as in young

6. Muscle Function: Endurance Capacity • endurance capacity appears preserved • recovery of contractile properties after fatiguing work slower • (Davies et al, 1983, 1984; Larsson, 1979)

7. Muscle Morphology: Fiber Type Distribution • (previous lit.) muscle biopsy studies (Gollnick et al, 1972; Green, 1986, rev.) • 10-30% increase in slow twitch fiber number • selective fast twitch fiber loss • (recent lit.) cadaver whole muscle studies (Lexall et al, 1988, 1989); surgical resectionings (Sato, 1984; Grimby et al , 1982, 1984) • no preferential loss of fiber type • number with ageing

8. Muscle Fiber Type Distribution • total muscle fiber number reduction of about 25% by 70 years (likely result of loss motor units) • Brooks and Faulkner (1994) suggest motor unit loss leads to reinnervation, preferentially by slow motor neurons, with an increase in the proportion of slow versus fast muscle fibers (biopsy studies)

9. Muscle Fiber Size (biopsy and whole muscle cross sectional studies [Lexall et al, 1988]): slow twitch fiber (Type I) area maintained fast twitch fiber (Type II) area decreased 25% between 20-80 years greatest loss in fast fatigueable (Type IIb) CONCLUDE: decrease CSA related to decrease in fast twitch fiber type size - (atrophy, loss of muscle protein,blood, enzymes)

10. Muscle Blood Flow • Capillarization - few studies • appears little changed in active old • decreased in sedentary old • decrease effectiveness of vasodilation with activity -- shunting of blood to active tissue • (??decrease sensitivity to circulating norepinephrine and epinephrine) • (??decrease ability of muscle to exchange metabolites across thickened basement membrane)

11. Muscle Metabolic Activity • ANNAEROBIC: • little change in glycolytic enzymes (3-15% or less) • little change in high energy phosphates (CP) • AEROBIC: • oxidative enzymes • little or no change in active older people • 20-40% decrease in sedentary older people • (Coggan et al, 1992; • Meredith et al, 1989)

12. Microscopic Changes in Muscle • sarcolemma leakage • thickening of the sarcolemma • disorganization of myofibrils Little evidence for myopathic changes in aging muscle. (except: dehydration, K+ moves out, muscle function declines recovery from damage – DOMS)

13. Neuromuscular Changes in with Aging • decrease number of motor units (25-30% decrease in spinal cord motoneurons) • prolonged contraction time • lower threshold firing rate (for remaining units) Result: Increased EMG for a given level of force production

14. Review of Connective Tissue Physiology Structure and Components: cells - fibroblast fibers - collagen elastin ground substance - glycosaminoglycans, GAGs (linked to protein =proteoglycans) associated proteins - fibronectin and laminin

15. Aging Changes in Connective Tissues in connective tissue cells: few

16. Aging Changes in Connective Tissues in fibers: collagen - decreased solubility, reducible cross linkages stabilize, increased rigidity elastin - decreased production, increased fragmentation, rupture, loss of “rebound”

17. Aging Changes in Connective Tissues in ground substance: Aggrecan = proteoglycan of articular cartilage, binds a lot of water changes in GAGS: decreased chondroitin-4-SO4 , changed to chondroitin-6-SO4 increased keratan SO4

18. Aging Changes in Connective Tissues Aggrecan - degradation of protein core Hyalauron - smaller size, less link protein Result more unbound GAGS - smaller fragments, diffuse into joint fluid

19. Aging Changes on Articular Cartilage Performance loss of hydrostatic lubrication: decrease compressibility increase in subchondral fractures inflammation - pain / spasm infection ischemia septicemia

20. Aging Changes on Articular Cartilage Performance • loss of boundary lubrication: • cracking and fibrillation: • disrupts binding of fibronectin and laminin • exposes cartilage to degredative enzymes Review this lecture