W J Fink’s research while affiliated with Ball State University and other places

Studies of real and simulated microgravity exposure show the lower limb muscles atrophy to the greatest extent, with the calf muscles being most affected and most difficult to target with exercise countermeasures. This ground-based study examined the metabolic involvement of the thigh and calf muscles during two cycle exercise protocols (moderate and high intensity) central to the exercise countermeasures program on the International Space Station. Intramuscular glycogen and triglyceride levels were quantified in the vastus lateralis and soleus muscles before and after a moderate (current ISS prescription: 45 min at 55% VO(2max), 131 +/- 12 W) and high (proposed ISS prescription: 8 x 30-s intervals at 150% VO(2max), 459 +/- 34 W) intensity cycle exercise bout in nine individuals. During moderate intensity cycling, glycogen was significantly reduced in the vastus lateralis (114 +/- 27 mmol x kg(-1) dry weight) and remained unchanged in the soleus. High intensity cycling significantly reduced glycogen in both muscles, but the vastus lateralis (151 +/- 25 mmol x kg(-1) dry weight) used significantly more (-160%) than the soleus (59 +/- 11 mmol x kg(-1) dry weight). Intramuscular triglycerides were unchanged in both muscles at both intensities. These findings, coupled with other ground-based studies, provide strong support for high intensity cycling being a more appropriate component of the ISS prescription for upper and lower leg skeletal muscle health and cardiorespiratory fitness, although additional exercise paradigms that target the calf are warranted. These muscle-specific findings should be considered when designing exercise strategies for combating conditions of sarcopenia and muscle wasting on Earth.

We examined whole body aerobic capacity and myocellular markers of oxidative metabolism in lifelong endurance athletes (n=9, 81±1 y, 68±3 kg, BMI=23±1 kg/m(2)) and age-matched, healthy, untrained men (n=6; 82±1 y, 77±5 kg, BMI=26±1 kg/m(2)). The endurance athletes were cross-country skiers, including a former Olympic champion and several national/regional champions, with a history of aerobic exercise and participation in endurance events throughout their lives. Each subject performed a maximal cycle test to assess aerobic capacity (VO(2)max). Subjects had a resting vastus lateralis muscle biopsy to assess oxidative enzymes (citrate synthase and βHAD) and molecular (mRNA) targets associated with mitochondrial biogenesis (PGC-1α and Tfam). The octogenarian athletes had a higher (P<0.05) absolute (2.6±0.1 vs. 1.6±0.1 L•min(-1)) and relative (38±1 vs. 21±1 ml•kg(-1)•min(-1)) VO(2)max, ventilation (79±3 vs. 64±7 L•min(-1)), heart rate (160±5 vs. 146±8 b•min(-1)), and final workload (182±4 vs. 131±14 watts). Skeletal muscle oxidative enzymes were 54% (citrate synthase) and 42% (βHAD) higher (P<0.05) in the octogenarian athletes. Likewise, basal PGC-1α and Tfam mRNA were 135% and 80% greater (P<0.05) in the octogenarian athletes. To our knowledge, the VO(2)max of the lifelong endurance athletes is the highest recorded in humans >80 y of age and comparable to non-endurance trained men 40 years younger. The superior cardiovascular and skeletal muscle health profile of the octogenarian athletes provides a large functional reserve above the aerobic frailty threshold and is associated with lower risk for disability and mortality.

Abstract: PURPOSE: To examine whole body aerobic capacity and myocellular markers of oxidative capacity in lifelong endurance athletes (n=9, 81±1 y, 68±3 kg, BMI=23±1 kg/m2) and compare to age-matched, independent living, healthy men (n=6; 82±1 y, 77±5 kg, BMI=26±1 kg/m2). The endurance athletes were cross-country skiers, including a former Olympic champion and several national/regional champions, with a history of aerobic exercise and frequent participation in an annual 90 km ski race and other related endurance events throughout their entire adult life. METHODS: Each subject performed a maximal test on a cycle ergometer to assess aerobic capacity (VO2max). Subjects also had a resting muscle biopsy from the vastus lateralis to assess oxidative enzymes (citrate synthase (CS) and βHAD) and molecular (mRNA) targets associated with mitochondrial biogenesis (PGC-1α and Tfam). RESULTS: The lifelong endurance athletes had a higher (P<0.05) absolute (2.6±0.1 vs. 1.6±0.1 l/min) and relative (38±1 vs. 21±1 ml/kg/min) VO2max, ventilation (79±3 vs. 64±7 l/min), heart rate (160±5 vs. 146±8 b/min), and final work rate (182±4 vs. 131±14 watts). Skeletal muscle oxidative enzymes were 54% (CS) and 42% (βHAD) higher (P<0.05) in the endurance athletes compared with the non-athletic men. Likewise, the endurance athletes PGC-1α and Tfam mRNA were 135% and 80% greater (P<0.05) compared with the non-athletes. CONCLUSION: To our knowledge, the VO2max data obtained from lifelong endurance athletes are the highest recorded in humans >80 y of age and comparable to non-endurance trained men 40-50 years younger. The superior maximal oxygen uptake was complemented by the skeletal muscle oxidative profile at the cellular and molecular level. These data provide unique insights into the endurance phenotype for cardiovascular and skeletal muscle health of elite octogenarian athletes.

Two pathways that have been implicated for cellular growth and development in response to muscle contraction are the extracellular signal-regulated kinase (ERK1/2) and Akt signaling pathways. Although these pathways are readily stimulated after exercise, little is known about how nutritional status may affect stimulation of these pathways in response to resistance exercise in human skeletal muscle. To investigate this, experienced cyclists performed 30 repetitions of knee extension exercise at 70% of one repetition maximum after a low (2%) or high (77%) carbohydrate (LCHO or HCHO) diet, which resulted in low or high (approximately 174 or approximately 591 mmol/kg dry wt) preexercise muscle glycogen content. Muscle biopsies were taken from the vastus lateralis before, approximately 20 s after, and 10 min after exercise. ERK1/2 and p90 ribosomal S6 kinase phosphorylation increased (P < or = 0.05) 10 min after exercise, regardless of muscle glycogen availability. Akt phosphorylation was elevated (P < 0.05) 10 min after exercise in the HCHO trial but was unaffected after exercise in the LCHO trial. Mammalian target of rapamycin phosphorylation was similar to that of Akt during each trial; however, change or lack of change was not significant. In conclusion, the ERK1/2 pathway appears to be unaffected by muscle glycogen content. However, muscle glycogen availability appears to contribute to regulation of the Akt pathway, which may influence cellular growth and adaptation in response to resistance exercise in a low-glycogen state.

The significance and relevance of the topics being discussed in this text is under scored by Westerhoff’s (2000) suggestion that biochemistry is poised to make major advances in this century, similar to those made in physics in the 20th century. He anticipates that, to understand the nonlinear kinetic interactions between molecules and interpret the vast quantities of data becoming available, biochemistry may soon become as computation-intensive as elementary particle physics. The papers in this book should contribute to that process.

Renal insufficiency is associated with altered vitamin B-6 metabolism. We have observed high concentrations of 4-pyridoxic acid, the major catabolite of vitamin B-6 metabolism, in plasma during renal insufficiency. The objective was to evaluate the renal handling of 4-pyridoxic acid and the effects of renal dysfunction on vitamin B-6 metabolism. We measured the renal clearance of 4-pyridoxic acid and creatinine in 17 nonpregnant, 17 pregnant, and 16 lactating women. We then examined the influence of vitamin B-6 or alkaline phosphatase activity on the ratio of 4-pyridoxic acid to pyridoxal (PA:PL) in plasma in 10 men receiving a low (0.4 mg pyridoxine.HCl/d) or high (200 mg pyridoxine.HCl/d) vitamin B-6 intake for 6 wk, in 10 healthy subjects during a 21-d fast, in 1235 plasma samples from 799 people screened for hypophosphatasia, and in 67 subjects with a range of serum creatinine concentrations. Renal clearance of 4-pyridoxic acid was 232 +/- 94 mL/min in nonpregnant women, 337 +/- 140 mL/min in pregnant women, and 215 +/- 103 mL/min in lactating healthy women. These values were approximately twice the creatinine clearance, indicating that 4-pyridoxic acid is at least partially eliminated by tubular secretion. Elevated plasma creatinine concentrations were associated with marked elevations in 4-pyridoxic acid and PA:PL. PA:PL was not affected by wide variations in vitamin B-6 intake or by the wide range of pyridoxal-P concentrations encountered while screening for hypophosphatasia. Plasma 4-pyridoxic acid concentrations are markedly elevated in renal insufficiency. Plasma PA:PL can distinguish between increases in 4-pyridoxic acid concentrations due to increased dietary intake and those due to renal insufficiency.

This investigation examined the effects of 4 weeks of non-dominant arm unloading on the functional and structural characteristics of the triceps brachii muscle of six normo-active college-age males (age: 23 +/- 1 years, height: 176 +/- 4 cm, weight: 76 +/- 6 kg). The primary intention of this study was to determine if arm unloading is an effective analogue for simulating the effects of weightlessness on human skeletal muscle. Subjects were tested 2-3 days preceding unloading in a standard arm sling and following removal of the sling. The sling was worn during waking hours to unload the arm. Subjects were allowed to remove the sling during sleep and bathing. Torque production (Nm) during maximal isometric extension at 90 degrees significantly declined (P < 0.05) in response to unloading (53.93 +/- 5.07 to 47.90 +/- 5.92; 12%). There was no significant change (P > 0.05) in the force-velocity attributes of the triceps over the other measured velocities (1.05, 1.57, 2.09, 3.14, 4.19, 5.24 rad.s-1). Cross-sectional muscle area (CSA) of the upper arm was smaller (44.3 +/- 2.7 to 42.4 +/- 2.5 cm2; 4%) following 4 weeks of unloading (P < 0.05). Histochemical analysis of individual muscle fibres demonstrated reductions in fibre CSA of 27 and 18% for type I and type II fibres, respectively. However, these changes were not statistically significant. Electrophoretic analysis of muscle samples revealed a significant increase (40 +/- 7 to 58 +/- 4%, pre- and post-, respectively) in myosin heavy chain (MHC) type II isoforms following unloading. Reductions in type I MHC isoform composition failed to reach statistical significance (P < 0.08). Amplitude of the integrated electromyographic (IEMG) signal during maximal isometric contraction of the long head of the triceps decreased by 21% in response to the 4-week unloading period (P < 0.05). The changes in triceps, muscle structure and function found with arm unloading are similar in magnitude and direction to data obtained from humans following exposure to real and simulated weightlessness. These findings demonstrate that arm unloading produces some of the effects seen in response to weightlessness in muscles of the upper arm and provides potential for an additional model to simulate the effects of microgravity on human skeletal muscle.