admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

mTORC1 is an important regulator of muscle mass but how it is modulated by oxygen and nutrients is not completely understood. We show that loss of the prolyl hydroxylase domain isoform 1 oxygen sensor in mice (PHD1KO) reduces muscle mass. PHD1KO muscles show impaired mTORC1 activation in response to leucine whereas mTORC1 activation by growth factors or eccentric contractions was preserved. The ability of PHD1 to promote mTORC1 activity is independent of its hydroxylation activity but is caused by decreased protein content of the leucyl tRNA synthetase (LRS) leucine sensor. Mechanistically, PHD1 interacts with and stabilizes LRS. This interaction is promoted during oxygen and amino acid depletion and protects LRS from degradation. Finally, elderly subjects have lower PHD1 levels and LRS activity in muscle from aged versus young human subjects. In conclusion, PHD1 ensures an optimal mTORC1 response to leucine after episodes of metabolic scarcity.

/pdf/phd1-controls-muscle-mtorc1-in-a-hydroxylation-independent-146drs5jvm.pdf

PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase.

Are designed landscapes conceived as geometric compositions or abstractions of nature incompatible with sustainable design? Does mimesis result in the only truly sustainable form in the landscape? This paper attempts to answer these questions by drawing on the observations of practitioners and educators in the field as well as investigating a range of built work for sustainable qualities. The built work is categorized according to four approaches to form genesis, geometric composition, abstractions of nature, mimesis, and combinations of the three. It is suggested here that there is no single formal strategy that must be used in order to achieve sustainability.

Summary comments

The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans

Skeletal muscle demonstrates extraordinary mutability in its responses to exercise of different modes, intensity, and duration, which must involve alterations of muscle protein turnover, both acutely and chronically. Here, we bring together information on the alterations in the rates of synthesis and degradation of human muscle protein by different types of exercise and the influences of nutrition, age, and sexual dimorphism. Where possible, we summarize the likely changes in activity of signaling proteins associated with control of protein turnover. Exercise of both the resistance and nonresistance types appears to depress muscle protein synthesis (MPS), whereas muscle protein breakdown (MPB) probably remains unchanged during exercise. However, both MPS and MPB are elevated after exercise in the fasted state, when net muscle protein balance remains negative. Positive net balance is achieved only when amino acid availability is increased, thereby raising MPS markedly. However, postexercise-increased amino acid availability is less important for inhibiting MPB than insulin, the secretion of which is stimulated most by glucose availability, without itself stimulating MPS. Exercise training appears to increase basal muscle protein turnover, with differential responses of the myofibrillar and mitochondrial protein fractions to acute exercise in the trained state. Aging reduces the responses of myofibrillar protein and anabolic signaling to resistance exercise. There appear to be few, if any, differences in the response of young women and young men to acute exercise, although there are indications that, in older women, the responses may be blunted more than in older men.

Human muscle protein synthesis and breakdown during and after exercise

Context A diminished muscle anabolic response to protein nutrition may underpin age-associated muscle loss. Objective To determine how chronological and biological aging influence myofibrillar protein synthesis (MyoPS). Design Cross-sectional comparison. Setting Clinical research facility. Participants Ten older lean [OL: 71.7 ± 6 years; body mass index (BMI) ≤25 kg ⋅ m-2], 7 older obese (OO: 69.1 ± 2 years; BMI ≥30 kg ⋅ m-2), and 18 young lean (YL) individuals (25.5 ± 4 years; BMI ≤25 kg ⋅ m-2). Intervention Skeletal muscle biopsies obtained during a primed-continuous infusion of l-[ring-13C6]-phenylalanine. Main Outcome Measures Anthropometrics, insulin resistance, inflammatory markers, habitual diet, physical activity, MyoPS rates, and fiber-type characteristics. Results Fat mass, insulin resistance, inflammation, and type II fiber intramyocellular lipid were greater, and daily step count lower, in OO compared with YL and OL. Postprandial MyoPS rates rose above postabsorptive values by ∼81% in YL (P < 0.001), ∼38% in OL (P = 0.002, not different from YL), and ∼9% in OO (P = 0.11). Delta change in postprandial MyoPS from postabsorptive values was greater in YL compared with OL (P = 0.032) and OO (P < 0.001). Absolute postprandial MyoPS rates and delta postprandial MyoPS change were associated with step count (r2 = 0.33; P = 0.015) and leg fat mass (r2 = 0.4; P = 0.006), respectively, in older individuals. Paradoxically, lean mass was similar between groups, and muscle fiber area was greater in OO vs OL (P = 0.002). Conclusion Age-related muscle anabolic resistance is exacerbated in obese inactive individuals, with no apparent detriment to muscle mass.

https://research.birmingham.ac.uk/portal/files/44612977/Smeuninx_et_al_Age_related_anabolic_resistance_JCEM.pdf

Age-Related Anabolic Resistance of Myofibrillar Protein Synthesis Is Exacerbated in Obese Inactive Individuals.

https://research.birmingham.ac.uk/portal/files/52804618/McKendry_et_al_Muscle_morphology_and_performance_Ageing_Research_Rev.pdf

Muscle morphology and performance in master athletes: A systematic review and meta-analyses.

Skeletal muscle plays a pivotal role in the maintenance of physical and metabolic health and, critically, mobility. Accordingly, strategies focused on increasing the quality and quantity of skeletal muscle are relevant, and resistance exercise is foundational to the process of functional hypertrophy. Much of our current understanding of skeletal muscle hypertrophy can be attributed to the development and utilization of stable isotopically labeled tracers. We know that resistance exercise and sufficient protein intake act synergistically and provide the most effective stimuli to enhance skeletal muscle mass; however, the molecular intricacies that underpin the tremendous response variability to resistance exercise-induced hypertrophy are complex. The purpose of this review is to discuss recent studies with the aim of shedding light on key regulatory mechanisms that dictate hypertrophic gains in skeletal muscle mass. We also aim to provide a brief up-to-date summary of the recent advances in our understanding of skeletal muscle hypertrophy in response to resistance training in humans.

Recent advances in understanding resistance exercise training-induced skeletal muscle hypertrophy in humans.

Skeletal muscle plays an indispensable role in metabolic health and physical function. A decrease in muscle mass and function with advancing age exacerbates the likelihood of mobility impairments, disease development, and early mortality. Therefore, the development of non-pharmacological interventions to counteract sarcopenia warrant significant attention. Currently, resistance training provides the most effective, low cost means by which to prevent sarcopenia progression and improve multiple aspects of overall health. Importantly, the impact of resistance training on skeletal muscle mass may be augmented by specific dietary components (i.e., protein), feeding strategies (i.e., timing, per-meal doses of specific macronutrients) and nutritional supplements (e.g., creatine, vitamin-D, omega-3 polyunsaturated fatty acids etc.). The purpose of this review is to provide an up-to-date, evidence-based account of nutritional strategies to enhance resistance training-induced adaptations in an attempt to combat age-related muscle mass loss. In addition, we provide insight on how to incorporate the aforementioned nutritional strategies that may support the growth or maintenance of skeletal muscle and subsequently extend the healthspan of older individuals.

/pdf/nutritional-supplements-to-support-resistance-exercise-in-5fkcxyaqpp.pdf

Nutritional Supplements to Support Resistance Exercise in Countering the Sarcopenia of Aging.

In vitro and in vivo studies described the myokine IL-15 and its receptor IL-15Rα as anabolic/anti-atrophy agents, however, the protein expression of IL-15Rα has not been measured in human skeletal muscle and data regarding IL-15 expression remain inconclusive. The purpose of the study was to determine serum and skeletal muscle IL-15 and IL-15Rα responses to resistance exercise session and to analyze their association with myofibrillar protein synthesis (MPS). Fourteen participants performed a bilateral leg resistance exercise composed of four sets of leg press and four sets of knee extension at 75% 1RM to task failure. Muscle biopsies were obtained at rest, 0, 4 and 24 hours post-exercise and blood samples at rest, mid-exercise, 0, 0.3, 1, 2, 4 and 24 hours post-exercise. Serum IL-15 was increased by ~5.3-fold immediately post-exercise, while serum IL-15Rα decreased ~75% over 1 hour post-exercise (P<.001). Skeletal muscle IL-15Rα mRNA and protein expression were increased at 4 hours post-exercise by ~2-fold (P<.001) and ~1.3-fold above rest (P=.020), respectively. At 24 hours post-exercise, IL-15 (P=.003) and IL-15Rα mRNAs increased by ~2-fold (P=.002). Myofibrillar fractional synthetic rate between 0-4 hours was associated with IL-15Rα mRNA at rest (r=.662, P=.019), 4 hours (r=.612, P=.029), and 24 hours post-exercise (r=.627, P=.029). Finally, the muscle IL-15Rα protein up-regulation was related to Leg press 1RM (r=.688, P=.003) and total weight lifted (r=.628, P=.009). In conclusion, IL-15/IL-15Rα signaling pathway is activated in skeletal muscle in response to a session of resistance exercise.

/pdf/skeletal-muscle-il-15-il-15ra-and-myofibrillar-protein-1mgmdjb6df.pdf

James McKendry

Papers

Age-Related Anabolic Resistance of Myofibrillar Protein Synthesis Is Exacerbated in Obese Inactive Individuals.

Muscle morphology and performance in master athletes: A systematic review and meta-analyses.

Recent advances in understanding resistance exercise training-induced skeletal muscle hypertrophy in humans.

Nutritional Supplements to Support Resistance Exercise in Countering the Sarcopenia of Aging.

Skeletal muscle IL-15/IL-15Rα and myofibrillar protein synthesis after resistance exercise.