Biological aging is associated with progressive damage accumulation, loss of organ reserves, and systemic inflammation ('inflammaging'), which predispose for a wide spectrum of chronic diseases, ...including several types of cancer. In contrast, aerobic exercise training (AET) reduces inflammation, lowers all-cause mortality, and enhances both health and lifespan. In this study, we examined the benefits of early-onset, lifelong AET on predictors of health, inflammation, and cancer incidence in a naturally aging mouse model (C57BL/J6). Lifelong, voluntary wheel-running (O-AET; 26-month-old) prevented age-related declines in aerobic fitness and motor coordination vs. age-matched, sedentary controls (O-SED). AET also provided partial protection against sarcopenia, dynapenia, testicular atrophy, and overall organ pathology, hence augmenting the 'physiologic reserve' of lifelong runners. Systemic inflammation, as evidenced by a chronic elevation in 17 of 18 pro- and anti-inflammatory cytokines and chemokines (P < 0.05 O-SED vs. 2-month-old Y-CON), was potently mitigated by lifelong AET (P < 0.05 O-AET vs. O-SED), including master regulators of the cytokine cascade and cancer progression (IL-1β, TNF-α, and IL-6). In addition, circulating SPARC, previously known to be upregulated in metabolic disease, was elevated in old, sedentary mice, but was normalized to young control levels in lifelong runners. Remarkably, malignant tumours were also completely absent in the O-AET group, whereas they were present in the brain (pituitary), liver, spleen, and intestines of sedentary mice. Collectively, our results indicate that early-onset, lifelong running dampens inflammaging, protects against multiple cancer types, and extends healthspan of naturally-aged mice.
Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in ...injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline, immediately after 10 min of massage treatment, and after a 2.5-hour period of recovery. We found that massage activated the mechanotransduction signaling pathways focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2), potentiated mitochondrial biogenesis signaling nuclear peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and mitigated the rise in nuclear factor κB (NFκB) (p65) nuclear accumulation caused by exercise-induced muscle trauma. Moreover, despite having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and reduced heat shock protein 27 (HSP27) phosphorylation, thereby mitigating cellular stress resulting from myofiber injury. In summary, when administered to skeletal muscle that has been acutely damaged through exercise, massage therapy appears to be clinically beneficial by reducing inflammation and promoting mitochondrial biogenesis.
A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the ...proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities.
Metabolic Syndrome (MetS) affects hundreds of millions of individuals and constitutes a major cause of morbidity and mortality worldwide. Obesity is believed to be at the core of metabolic ...abnormalities associated with MetS, including dyslipidemia, insulin resistance, fatty liver disease and vascular dysfunction. Although previous studies demonstrate a diverse array of naturally occurring antioxidants that attenuate several manifestations of MetS, little is known about the (i) combined effect of these compounds on hepatic health and (ii) molecular mechanisms responsible for their effect.
We explored the impact of a metabolic enhancer (ME), consisting of 7 naturally occurring antioxidants and mitochondrial enhancing agents, on diet-induced obesity, hepatic steatosis and atherogenic serum profile in mice.
Here we show that a diet-based ME supplementation and exercise have similar beneficial effects on adiposity and hepatic steatosis in mice. Mechanistically, ME reduced hepatic ER stress, fibrosis, apoptosis, and inflammation, thereby improving overall liver health. Furthermore, we demonstrated that ME improved HFD-induced pro-atherogenic serum profile in mice, similar to exercise. The protective effects of ME were reduced in proprotein convertase subtilisin/kexin 9 (PCSK9) knock out mice, suggesting that ME exerts it protective effect partly in a PCSK9-dependent manner.
Our findings suggest that components of the ME have a positive, protective effect on obesity, hepatic steatosis and cardiovascular risk and that they show similar effects as exercise training.
Background. Cosmetic products contribute considerably to the incidence of contact dermatitis. In response to a resolution of the Council of Europe, the National Institute for Public Health and the ...Environment (RIVM) in The Netherlands set up a pilot project to report undesirable effects attributed to cosmetic products.
Objectives. To provide an overview of undesirable effects attributed to cosmetic products and to identify the ingredients involved. The information could contribute to the assessment of whether current EU legislation on cosmetics provides adequate protection.
Patients/methods. General practitioners, dermatologists and consumers in The Netherlands completed questionnaires on reported undesirable effects of cosmetics. Dermatologists also carried out patch tests and, where necessary, tests with specific batch ingredients of the associated cosmetic product. A website and a public awareness campaign were launched to encourage consumers to report undesirable effects.
Results. Between July 2009 and May 2011, the RIVM received more than 1600 reports. Severe undesirable effects were claimed in 1–4% of the cases. The most frequently reported cosmetic products were make‐up and moisturisers, and the most frequently identified allergens were isothiazolinones and fragrance ingredients. Three patients tested positive for co‐polymers/cross‐polymers.
Conclusions. Further investigations are recommended on the prevalence of isothiazolinone‐induced allergic contact dermatitis and the allergenic potential of co‐polymers/cross‐polymers.
Introduction: Structural evidence of exercise‐induced muscle disruption has traditionally involved histological analysis of muscle tissue obtained by needle biopsy, however, there are multiple ...limitations with this technique. Recently, diffusion tensor magnetic resonance imaging (DT‐MRI) has been successfully demonstrated to noninvasively assess skeletal muscle abnormalities induced by traumatic injury. Methods: To determine the potential for DT‐MRI to detect musculoskeletal changes after a bout of eccentric exercise, 10 healthy men performed 300 eccentric actions on an isokinetic dynamometer. DT‐MRI measurements and muscle biopsies from the vastus lateralis were obtained before and 24 h post‐exercise. Results: Z‐band streaming was higher 24 h post‐exercise compared with baseline (P < 0.05). The histological indices of damage coincided with changes in DT‐MRI parameters of fractional anisotropy (FA) and apparent diffusion coefficient; reflecting altered skeletal muscle geometry (P < 0.05). Z‐band streaming quantified per fiber correlated with FA (r = −0.512; P < 0.05). Conclusions: DT‐MRI can detect changes in human skeletal muscle structure following eccentric exercise. Muscle Nerve 46: 42–50, 2012
Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long‐term side effects. To determine the potential therapeutic benefit from four nutritional compounds ...(creatine monohydrate, conjugated linoleic acid, α‐lipoic acid, and β‐hydroxy‐β‐methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P < 0.05), decreased grip strength fatigue (P < 0.05), decreased number of internalized myonuclei (P < 0.01), and smaller retroperitoneal fat pad stores (P < 0.001). This study provided evidence for therapeutic benefit from a four‐compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD. Muscle Nerve, 2005
Creatine kinase, found in osteoblasts, is an enzyme that is upregulated in response to interventions that enhance bone mass accretion. Creatine monohydrate supplementation can increase fat-free mass ...in young healthy men and women and can reduce markers of bone breakdown in boys with Duchenne muscular dystrophy.
The objective of this study was to determine the influence of supplementation with creatine monohydrate on bone structure and function in growing rats, to establish a therapeutic model.
Creatine monohydrate (2% w.w.) (CR; N = 16) or standard rat chow (CON; N = 16) was fed to Sprague-Dawley rats beginning at 5 wk of age, for 8 wk. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy x-ray absorptiometry at the beginning and end of the protocol. The rats were sacrificed, and one femur was removed for the determination of mechanical properties.
The CR-treated rats showed greater lumbar BMD and femoral bending load at failure compared with the CON rats (P < 0.05).
Together, these data suggest that creatine monohydrate potentially has a beneficial influence on bone function and structure; further investigation is warranted into its effect on bone functional properties and its effects in disorders associated with bone loss.
A fully three-dimensional, finite-difference time-domain (FDTD) model of a ground-penetrating radar is described. The FDTD simulation completely models the transmitting and receiving antennas, the ...antenna feeds, the dispersive Earth, and the buried object. Results of scattering from three different buried cylindrical pipes are compared to previously measured results for a one-third size scale model of an actual radar and are shown to be in good agreement.
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