Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These mice have a shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary disease, cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of Klotho has opposite effects, extending lifespan. In humans, Klotho levels decline with age, chronic kidney disease, diabetes, Alzheimer's disease and other conditions. Low Klotho levels correlate with an increase in the death rate from all causes. Klotho acts either as an obligate coreceptor for fibroblast growth factor 23 (FGF23), or as a soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced in the kidneys, but also in the brain, pancreas and other tissues. On renal tubular-cell membranes, it associates with FGF receptors to bind FGF23. Produced in bones, FGF23 regulates renal excretion of phosphate (phosphaturic effect) and vitamin D metabolism. Lack of Klotho or FGF23 results in hyperphosphatemia and hypervitaminosis D. With age, human renal function often deteriorates, lowering Klotho levels. This appears to promote age-related pathology. Remarkably, Klotho inhibits four pathways that have been linked to aging in various ways: Transforming growth factor ß (TGF-ß), insulin-like growth factor 1 (IGF-1), Wnt and NF-κB. These can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis and neoplasia. Furthermore, Klotho increases cell-protective antioxidant enzymes through Nrf2 and FoxO. In accord, preclinical Klotho therapy ameliorated renal, cardiovascular, diabetes-related and neurodegenerative diseases, as well as cancer. s-Klotho protein injection was effective, but requires further investigation. Several drugs enhance circulating Klotho levels, and some cross the blood-brain barrier to potentially act in the brain. In clinical trials, increased Klotho was noted with renin-angiotensin system inhibitors (losartan, valsartan), a statin (fluvastatin), mTOR inhibitors (rapamycin, everolimus), vitamin D and pentoxifylline. In preclinical work, antidiabetic drugs (metformin, GLP-1-based, GABA, PPAR-γ agonists) also enhanced Klotho. Several traditional medicines and/or nutraceuticals increased Klotho in rodents, including astaxanthin, curcumin, ginseng, ligustilide and resveratrol. Notably, exercise and sport activity increased Klotho. This review addresses molecular, physiological and therapeutic aspects of Klotho.

Stimulated biofeedback training for a child with Becker muscular dystrophy and compartment syndrome in the left forearm.

BACKGROUND: Muscular dystrophy negatively affects ambulation, mobility, self-care, and community involvement. Neonatal compartment syndrome (NCS) causes loss of muscle strength, sensory problems, and limb dysfunction. Patients with Becker Muscular Dystrophy (BMD) and/or NCS may benefit from individualized rehabilitation to improve function. PURPOSE: This case report describes stimulated biofeedback training (SBT) to improve the functional level, muscle strength, balance, and hand function in a child with BMD and NCS. CASE DESCRIPTION: An 8-year-old male patient with BMD and NCS in the left forearm received 12-weeks of SBT. The functional level was assessed by the Motor Function Measurement-32 (MFM-32), muscle strength by a hand-held dynamometer, balance by the Neurocom Balance Master, and upper limb function by the Quality of Upper Extremity Skills Test (QUEST) at the initial examination, after 6 weeks and after 12 weeks of treatment. Laboratory tests to monitor changes in serum creatine kinase were performed throughout the episode of care. OUTCOMES: The laboratory values remained within the appropriate range to continue SBT. Functional level, hand function, hip, and knee flexion/extension strength, and dorsiflexion strength improved. CONCLUSIONS: This case report suggests that SBT safely and effectively improved functional level, muscle strength, and hand function in this child with BMD and NCS.

Assessing the knee flexion range of motion after total knee arthroplasty: Technology versus senses.

INTRODUCTION: Following total knee arthroplasty surgery, attention should be paid to post-operative knee range of motion to achieve daily activities. Goniometer assessment is widely used to assess the range of motion in the post-operative period. This study aimed to determine the inter-rater ability of a smartphone application and visual estimation of the knee joint after total knee arthroplasty among different professions that commonly work together and compare whether any method is superior to another. METHOD: Range of motion measurements was performed by four clinicians as two physiotherapists and two orthopedic fellows. They utilized the Goniometer Reports application for smartphones, universal goniometer, and visual estimation to measure angles of knees which was operated. A two-way mixed model of intra-class correlation coefficient (ICC) with a 95% confidence level was used to assess inter-rater reliability. RESULTS: Thirteen patients (11 female) and 20 knees (10 right) were assessed. The ICCs were found excellent both for between methods and between raters. CONCLUSION: Our results show that technology seems a more accurate way to determine the knee range of motion after knee arthroplasty compared to senses. However, in lack of technological resources or time, or to avoid possible infection, visual estimation also could provide useful information.