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Metabolic dysfunctions are among the best documented hallmarks of ageing. Cardiovascular disease, Alzheimer's disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. We studied the effect of suppressing ketosis in 10 lean (BMI 20.5 kg/m2 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9 years) maintaining nutritional ketosis (NK) for an average of 3.9 years (± 2.3) who underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Ketosis suppression significantly increased insulin, 1.83-fold (p = 0.0006); glucose, 1.17-fold (p = 0.0088); homeostasis model assessment for insulin resistance (HOMA-IR), 2.13-fold (p = 0.0008); leptin, 3.35-fold (p = 0.0010); total osteocalcin, 1.63-fold (p = 0.0138); and uncarboxylated osteocalcin, 1.98-fold (p = 0.0417) and significantly decreased beta-hydroxybutyrate, 13.50-fold (p = 0.0012) and glucagon-like peptide-1 (GLP-1), 2.40-fold (p = 0.0209). Sustained NK showed no adverse health effects and may mitigate hyperinsulinemia. All biomarkers returned to basal P1 levels after removing the intervention for SuK, indicating that metabolic flexibility was maintained with long-term euketonaemia. [ABSTRACT FROM AUTHOR]

In the pursuit of longevity and healthspan, we are challenged with first overcoming chronic diseases of ageing: cardiovascular disease, hypertension, cancer, dementias, type 2 diabetes mellitus. These are hyperinsulinaemia diseases presented in different tissue types. Hyperinsulinaemia reduces endogenous antioxidants, via increased consumption and reduced synthesis. Hyperinsulinaemia enforces glucose fuelling, consuming 4 NAD+ to produce 2 acetyl moieties; beta-oxidation, ketolysis and acetoacetate consume 2, 1 and 0, respectively. This decreases sirtuin, PARPs and oxidative management capacity, leaving reactive oxygen species to diffuse to the cytosol, upregulating aerobic glycolysis, NF-kB and cell division signalling. Also, oxidising cardiolipin, reducing oxidative phosphorylation (OXPHOS) and apoptosis ability; driving a tumourigenic phenotype. Over time, increasing senescent/pathological cell populations occurs, increasing morbidity and mortality. Beta-hydroxybutyrate, an antioxidant, metabolite and signalling molecule, increases synthesis of antioxidants via preserving NAD+ availability and enhancing OXPHOS capacity. Fasting and ketogenic diets increase ketogenesis concurrently decreasing insulin secretion and demand; hyperinsulinaemia inhibits ketogenesis. Lifestyles that maintain lower insulin levels decrease antioxidant catabolism, additionally increasing their synthesis, improving oxidative stress management and mitochondrial function and, subsequently, producing healthier cells. This supports tissue and organ health, leading to a better healthspan, the first challenge that must be overcome in the pursuit of youthful longevity. [ABSTRACT FROM AUTHOR]

Introduction: On of the most important challenges nowadays is to improve the health of workers globally. Since 2005, the World Health Organization (WHO), through its Regional Office for Europe, has recognized the importance of employee well-being and of the prevention of health problems in the workplace. Aim: The aim of the study was to describe the musculoskeletal profile of miners by recording the possible deficits and dysfunctions of their musculoskeletal system. One of its objectives was to create and implement educational material for the prevention and improvement of musculoskeletal diseases. Materials and method: The sample consisted of 100 Greek miners with an average age of 39 (±8) and 1.6 (±0.5) years of work experience in mine tunnels. The programme included the recording of musculoskeletal disorders and the evaluation of the subjects' knowledge for the prevention and management of musculoskeletal pain after the implementation of the programmme as well as their subsequent relationship with physical exercise and its benefits. Data collection was done through personal interview and questionnaires. The corresponding educational material was created in printed and electronic form, based on the results of the assessment. Training included theoretical and hands-on hourly seminars that lasted 4 months. Upon completion, employees were evaluated by answering questions related to their training material. Results: The results showed that most of the miners did not maintain the correct position during their work. The pain intensity was significantly dependent on area of body (Chi-Square(1)=12.36, p<0.001) and the scale of "physical-body health» showed higher scores in subjects who did not experience pain (F=4.26, p=0.042). Also following the implementation of the programme the knowledge of the employees regarding the prevention and treatment of musculoskeletal disorders was very good. Conclusions: According to the above, the implemented methodology was effective and can be applied to other working populations by adapting the training material accordingly. [ABSTRACT FROM AUTHOR]