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Recent work suggests human physiology is not well adapted to prolonged periods of inactivity, with time spent sitting increasing cardiovascular disease and mortality risk. Health risks from sitting are generally linked with reduced levels of muscle contractions in chair-sitting postures and associated reductions in muscle metabolism. These inactivity-associated health risks are somewhat paradoxical, since evolutionary pressures tend to favor energy-minimizing strategies, including rest. Here, we examined inactivity in a hunter-gatherer population (the Hadza of Tanzania) to understand how sedentary behaviors occur in a nonindustrial economic context more typical of humans' evolutionary history. We tested the hypothesis that nonambulatory rest in hunter-gatherers involves increased muscle activity that is different from chair-sitting sedentary postures used in industrialized populations. Using a combination of objectively measured inactivity from thigh-worn accelerometers, observational data, and electromygraphic data, we show that hunter-gatherers have high levels of total nonambulatory time (mean ± SD = 9.90 ± 2.36 h/d), similar to those found in industrialized populations. However, nonambulatory time in Hadza adults often occurs in postures like squatting, and we show that these "active rest" postures require higher levels of lower limb muscle activity than chair sitting. Based on our results, we introduce the Inactivity Mismatch Hypothesis and propose that human physiology is likely adapted to more consistently active muscles derived from both physical activity and from nonambulatory postures with higher levels of muscle contraction. Interventions built on this model may help reduce the negative health impacts of inactivity in industrialized populations.

This article discusses the relationship between aging, skeletal muscle physiology and physical inactivity. An analysis of lipoprotein lipase, triglyceride metabolism, and blood lipids is presented.

Research was conducted to examine the role of local contractile activity and muscle fiber type on lipoprotein lipase (LPL) regulation during exercise. A sample of female Sprague-Dawley rats which weighed approximately 175 g were allowed access to voluntary running wheels for 14-20 days. Results are in good agreement with the hypothesis that the effects of local contractile activity are important and sufficient to increase LPL expression during exercise.

Researchers have investigated the temporal expression pattern of messenger RNAs for insulin-like growth factor (IGF)-I, IGF-I receptor and IGF-II in the regenerating tibialis anterior muscle following injection of the myotoxic anesthetic bupivacaine in young, adult and old rats. Five days after injection, IGF-II mRNA was boosted 46-fold in young rats, but only fourfold in adult rats. The results indicate that the impairment of muscle regeneration is a maturation effect, rather than an aging effect.

The tissue water volume and extracellular water volume of isolated cat muscles were analyzed to determine the effects of pressure on water distribution during muscle stimulation. Quantitative analysis of water in isolated cat muscles by nonsteady tracers indicated the role of intracellular osmoles on pressure generation in muscle fluid uptake during exercise. Muscle stimulation also increased the levels of intracellular osmolarity and flow of solute-poor water into the cell.

The (RNA) ribonucleic acid-protein interaction in skeletal rat muscle was analyzed to determine the components of its 3'-untranslated region (3'-UTR) in the cytochrome c mRNA that responds to contractile activity. Prolonged stimulation of the skeletal muscle enhanced cytochrome c gene expression and concentration. Interactions between cytoplasmic proteins in the proximal region of 3'-UTR produced specific RNA-complexes.

Aging muscles do not exhibit a decline in the concentration of precursors to insulin-like growth factors so that these factors cannot account for the muscle atrophy that occurs with aging. The concentration of mRNA for insulin-like growth factors did increase between youth and middle age, but subsequent declines in the growth factors were not seen as the rats progressed from 12 to 24 months of age.

Sucrose on NaCl aid the examination of changes of distribution of fluid in isolated perfused cat calf muscle, induced by quick enhancements in plasma osmolality. The total transsarcolemmal flow is equal to the total transcapillary water flow during steady state, and therefore cell volume shrinkage is approximately equal to the increase in plasma volume. Reductions in intracellular water volume and total tissue water are identical, and there is no variation in steady state interstitial fluid transient with hypertonic NaCl and sucrose.

Abstract Background Partly because of functional genomics, there has been a major paradigm shift from solely thinking of skeletal muscle as contractile machinery to an understanding that it can have roles in paracrine and endocrine functions. Physical inactivity is an established risk factor for some blood clotting disorders. The effects of inactivity during sitting are most alarming when a person develops the enigmatic condition in the legs called deep venous thrombosis (DVT) or “coach syndrome,” caused in part by muscular inactivity. The goal of this study was to determine if skeletal muscle expresses genes with roles in hemostasis and if their expression level was responsive to muscular inactivity such as occurs in prolonged sitting. Methods Microarray analyses were performed on skeletal muscle samples from rats and humans to identify genes associated with hemostatic function that were significantly expressed above background based on multiple probe sets with perfect and mismatch sequences. Furthermore, we determined if any of these genes were responsive to models of physical inactivity. Multiple criteria were used to determine differential expression including significant expression above background, fold change, and non-parametric statistical tests. Results These studies demonstrate skeletal muscle tissue expresses at least 17 genes involved in hemostasis. These include the fibrinolytic factors tetranectin, annexin A2, and tPA; the anti-coagulant factors TFPI, protein C receptor, PAF acetylhydrolase; coagulation factors, and genes necessary for the posttranslational modification of these coagulation factors such as vitamin K epoxide reductase. Of special interest, lipid phosphate phosphatase-1 (LPP1/PAP2A), a key gene for degrading prothrombotic and proinflammatory lysophospholipids, was suppressed locally in muscle tissue within hours after sitting in humans; this was also observed after acute and chronic physical inactivity conditions in rats, and exercise was relatively ineffective at counteracting this effect in both species. Conclusions These findings suggest that skeletal muscle may play an important role in hemostasis and that muscular inactivity may contribute to hemostatic disorders not only because of the slowing of blood flow per se, but also potentially because of the contribution from genes expressed locally in muscles, such as LPP1.

Abstract Background The inactivity physiology paradigm proposes that sedentary behaviors, including sitting too much, are independent of the type of physical activity delineated for health in the Physical Activity Guidelines for Americans. Thus, we hypothesized that, when accounting for behaviors across the entire day, variability in the amount of time spent sitting would be independent of the inter-and intra-individual time engaged in sustained moderate-to-vigorous physical activity (MVPA). Methods Ninety-one healthy women, aged 40–75 years, completed a demographic questionnaire and assessment of height and weight. Participants wore the activPAL activity monitor for one week and time (minutes/day) spent sitting, standing, stepping, and in sustained bouts (bouts ≥10 minutes) of MVPA were quantified. The women were then stratified into groups based on weekly sustained MVPA. Additionally, each day of data collection for each participant was classified as either a “sufficient” MVPA day (≥ 30 min of MVPA) or an “insufficient” MVPA day for within-participant analyses. Results Time spent sitting, standing, and in incidental non-exercise stepping averaged 64, 28, and 11 hrs/week, respectively, and did not differ between groups with individuals meeting/exceeding the current exercise recommendation of 150 min/week of sustained MVPA in ≥10 minutes bouts (M = 294 min/week, SD = 22) compared to those with none or minimal levels (M= 20min/week, SD = 4). Time spent sitting (M = 9.1 hr/day, SD = 0.19 vs. M = 8.8 hr/day, SD = 0.22), standing (M = 3.9 hr/day, SD = 0.16 vs. M = 3.9 hr/day, SD = 0.15), and in intermittent stepping (M = 1.6 hr/day, SD = 0.07 vs. M = 1.6 hr/day, SD = 0.06) did not differ between days with (~55 min/day) and without recommended MVPA. Conclusions This study provides the first objective evidence that participation in sustained MVPA is unrelated to daily sitting duration in relatively healthy, middle and older-aged women. More research is needed to extend these findings to other populations and to inform distinct behavioral recommendations focused on sedentary time.

Abstract Background Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. Methods Using a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL). Results The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. Conclusions These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

Abstract: A shared goal of many researchers has been to discover how to improve health and prevent disease, through safely replacing a large amount of daily sedentary time with physical activity in everyone, regardless of age and current health status. This involves contrasting how different muscle contractile activity patterns regulate the underlying molecular and physiological responses impacting health‐related processes. It also requires an equal attention to behavioural feasibility studies in extremely unfit and sedentary people. A sound scientific principle is that the body is constantly sensing and responding to changes in skeletal muscle metabolism induced by contractile activity. Because of that, the rapid time course of health‐related responses to physical inactivity/activity patterns are caused in large part directly because of the variable amounts of muscle inactivity/activity throughout the day. However, traditional modes and doses of exercise fall far short of replacing most of the sedentary time in the modern lifestyle, because both the weekly frequency and the weekly duration of exercise time are an order of magnitude less than those for people sitting inactive. This can explain why high amounts of sedentary time produce distinct metabolic and cardiovascular responses through inactivity physiology that are not sufficiently prevented by low doses of exercise. For these reasons, we hypothesize that maintaining a high metabolic rate over the majority of the day, through safe and sustainable types of muscular activity, will be the optimal way to create a healthy active lifestyle over the whole lifespan. [ABSTRACT FROM AUTHOR]