Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease

Oxidative stress is proposed as an important factor in osteoarthritis (OA). To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA. SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin–Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression. All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin–Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression. This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function

Trail use, motivations and environmental attitudes of 3780 European mountain bikers: what is sustainable?

Background: The extent to which mountain biking impacts upon the environment is largely determined by rider behaviours. The purpose of this study was to gain a better understanding of how mountain bikers interact with the natural environment and explore their attitudes towards sustainability. Methods: 3780 European mountain bikers completed an online cross-sectional survey. Results: Connection to nature was an important source of motivation and the use of mountain bike trails has increased rider’s appreciation of and willingness to protect nature, with a large majority having taken direct action to do so. Mountain bikers are prepared to contribute towards trail maintenance through the provision of labour or financially. Although most mountain bikers make use of wet trails and illegal trails, incidence of conflict is relatively low. A range of characteristics were identified as being fundamental elements of sustainable trails, both in relation to the sustainability of the trail itself and in terms of wider environmental sustainability. Conclusions: European mountain bikers care about the sustainability of the natural environment. Self-reported attitudes and behaviours suggest a willingness to reduce environmental impact and actively protect nature

Ocean nutrient pathways associated with passage of a storm

Storms that affect ocean surface layer dynamics and primary production are a frequent occurrence in the open North Atlantic Ocean. In this study we use an interdisciplinary dataset collected in the region to quantify nutrient supply by two pathways associated with a storm event: entrainment of nutrients during a period of high wind forcing and subsequent shear-spiking at the pycnocline due to interactions of storm generated inertial currents with wind. The post-storm increase in surface layer nitrate (by ~20 mmol m?2) was predominantly driven by the first pathway: nutrient intrusion during the storm. Alignment of post-storm inertial currents and surface wind stress caused shear instabilities at the ocean pycnocline, forming the second pathway for nutrient transport into the euphotic zone. During the alignment period, pulses of high turbulent nitrate flux through the pycnocline (up to 1 mmol m?2 day?1; approximately 25 times higher than the background flux) were detected. However, the impact of the post-storm supply was an order of magnitude lower than during the storm due to the short duration of the pulses. Cumulatively, the storm passage was equivalent to 2.5-5 % of the nitrate supplied by winter convection and had a significant effect compared to previously reported (sub)-mesoscale dynamics in the region. As storms occur frequently, they can form an important component in local nutrient budgets

Capability and dependency in the Newcastle 85+ cohort study. Projections of future care needs

<p>Abstract</p> <p>Background</p> <p>Little is known of the capabilities of the oldest old, the fastest growing age group in the population. We aimed to estimate capability and dependency in a cohort of 85 year olds and to project future demand for care.</p> <p>Methods</p> <p>Structured interviews at age 85 with 841 people born in 1921 and living in Newcastle and North Tyneside, UK who were permanently registered with participating general practices. Measures of capability included were self-reported activities of daily living (ADL), timed up and go test (TUG), standardised mini-mental state examination (SMMSE), and assessment of urinary continence in order to classify interval-need dependency. To project future demand for care the proportion needing 24-hour care was applied to the 2008 England and Wales population projections of those aged 80 years and over by gender.</p> <p>Results</p> <p>Of participants, 62% (522/841) were women, 77% (651/841) lived in standard housing, 13% (106/841) in sheltered housing and 10% (84/841) in a care home. Overall, 20% (165/841) reported no difficulty with any of the ADLs. Men were more capable in performing ADLs and more independent than women. TUG validated self-reported ADLs. When classified by 'interval of need' 41% (332/810) were independent, 39% (317/810) required help less often than daily, 12% (94/810) required help at regular times of the day and 8% (67/810) required 24-hour care. Of care-home residents, 94% (77/82) required daily help or 24-hour care. Future need for 24-hour care for people aged 80 years or over in England and Wales is projected to increase by 82% from 2010 to 2030 with a demand for 630,000 care-home places by 2030.</p> <p>Conclusions</p> <p>This analysis highlights the diversity of capability and levels of dependency in this cohort. A remarkably high proportion remain independent, particularly men. However a significant proportion of this population require 24-hour care at home or in care homes. Projections for the next 20 years suggest substantial increases in the number requiring 24-hour care due to population ageing and a proportionate increase in demand for care-home places unless innovative health and social care interventions are found.</p

The Newcastle 85+ study: biological, clinical and psychosocial factors associated with healthy ageing: study protocol

<p>Abstract</p> <p>Background</p> <p>The UK, like other developed countries, is experiencing a marked change in the age structure of its population characterised by increasing life expectancy and continuing growth in the older fraction of the population. There is remarkably little up-to-date information about the health of the <it>oldest old </it>(over 85 years), demographically the fastest growing section of the population. There is a need, from both a policy and scientific perspective, to describe in detail the health status of this population and the factors that influence individual health trajectories. For a very large proportion of medical conditions, age is the single largest risk factor. Gaining new knowledge about why aged cells and tissues are more vulnerable to pathology is likely to catalyse radical new insights and opportunities to intervene. The aims of the Newcastle 85+ Study are to expose the spectrum of health within an inception cohort of 800 85 year-olds; to examine health trajectories and outcomes as the cohort ages and their associations with underlying biological, medical and social factors; and to advance understanding of the biological nature of ageing.</p> <p>Methods</p> <p>A cohort of 800 85 year olds from Newcastle and North Tyneside will be recruited at baseline and followed until the last participant has died. Eligible individuals will be <it>all </it>those who turn 85 during the year 2006 (i.e. born in 1921) and who are registered with a Newcastle or North Tyneside general practice. Participants will be visited in their current residence (own home or institution) by a research nurse at baseline, 18 months and 36 months. The assessment protocol entails a detailed multi-dimensional health assessment together with review of general practice medical records. Participants will be flagged with the NHS Central Register to provide details of the date and cause of death.</p> <p>Discussion</p> <p>The Newcastle 85+ Study will address key questions about health and health-maintenance in the 85+ population, with a particular focus on quantitative assessment of factors underlying variability in health, and on the relationships between health, nutrition and biological markers of the fundamental processes of ageing.</p

Feedback between p21 and reactive oxygen production is necessary for cell senescence

The sustained activation of CDKN1A (p21/Waf1/Cip1) by a DNA damage response induces mitochondrial dysfunction and reactive oxygen species (ROS) production via signalling through CDKN1A-GADD45A-MAPK14- GRB2-TGFBR2-TGFbeta in senescing primary human and mouse cells in vitro and in vivo.Enhanced ROS production in senescing cells generates additional DNA damage. Although this damage is repairable and transient, it elevates the average levels of DNA damage response permanently, thus forming a positive feedback loop.This loop is necessary and sufficient to maintain the stability of growth arrest until a ‘point of no return' is reached during establishment of senescence