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In a 5-year prospective study on idiopathic scoliosis, an attempt was made to elucidate the natural history of the disease and to determine which factors contribute to curve progression. A total of 85,622 children were examined for scoliosis in a prospective school screening study carried out in northwestern and central Greece. Curve progression was studied in 839 of the 1,436 children with idiopathic scoliosis of at least 10 degrees detected from the school screening program. Each child was followed clinically and roentgenographically for one to four follow-up visits for a mean of 3.2 years. Progression of the scoliotic curve was recorded in 14.7% of the children. Spontaneous improvement of at least 5 degrees was observed in 27.4% of them, with 80 children (9.5%) demonstrating complete spontaneous resolution. Eighteen percent of the patients remained stable, while the remaining patients demonstrated nonsignificant changes of less than 5 degrees in curve magnitude. A strong association was observed between the incidence of progression and the sex of the child, curve pattern, maturity, and to a lesser extent age and curve magnitude. More specifically, the following were associated with a high risk of curve progression: sex (girls); curve pattern (right thoracic and double curves in girls, and right lumbar curves in boys); maturity (girls before the onset of menses); age (time of pubertal growth spurt); and curve magnitude (> or = 30 degrees). On the other hand, left thoracic curves showed a weak tendency for progression. In conclusion, the findings of the present study strongly suggest that only a small percentage of scoliotic curves will undergo progression. The pattern of the curve according to curve direction and sex of the child was found to be a key indicator of which curves will progress. Eur Spine J

PURPOSE: To describe the study design and methodology of the Tromsø Eye Study (TES), and to describe visual acuity and refractive error in the study population.METHODS: The Tromsø Eye Study is a sub-study of the Tromsø Study, a population-based multipurpose longitudinal study in the municipality of Tromsø, Norway. The Tromsø Eye Study was a part of the sixth survey of the Tromsø Study, conducted from October 2007 through December 2008. The eye examination included information on self-reported eye diseases, assessment of visual acuity and refractive errors, retinal photography and optical coherence tomography. Retinal images were graded for diabetic retinopathy and age-related macular degeneration, and with computer-assisted measurements of arteriolar and venular diameters. In addition, TES researchers have access to the large comprehensive Tromsø Study database including physical examination results, carotid artery ultrasound, electrocardiogram, bone densitometry, cognitive tests, questionnaires, DNA, blood and urine samples and more from the present and the five previous surveys.RESULTS: Visual acuity was assessed in 6459 subjects and refraction in 6566 subjects aged 38-87 years. Snellen visual acuity CONCLUSION: Prevalence of visual impairment was low but increased with age. There was a trend towards hyperopia with age and no clinically relevant difference in refraction between the sexes. TES aims to provide epidemiological research on several eye and eye-related diseases. Owing to a comprehensive data collection, it has the opportunity to explore issues related to environmental factors, cognition and their interaction with diseases in this community.

SUMMARY: Currently used diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. These diagnostic measures associate differently to bone mineral density (BMD), as an example of muscle-related clinical outcome. These differences should be taken into account when studying sarcopenia.INTRODUCTION: Diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. To understand differences between these measures, we determined the association with respect to whole body BMD, as an example of muscle-related clinical outcome.METHODS: In the European cross-sectional study MYOAGE, 178 young (18-30 years) and 274 healthy old participants (69-81 years) were recruited. Body composition and BMD were evaluated using dual-energy X-ray densitometry. Diagnostic measures for sarcopenia were composed of lean mass as percentage of body mass, appendicular lean mass (ALM) as percentage of body mass, ALM divided by height squared (ALM/height(2)), knee extension torque, grip strength, walking speed, and Timed Up and Go test (TUG). Linear regression models were stratified for sex and age and adjusted for age and country, and body composition in separate models.RESULTS: Lean mass and ALM/height(2) were positively associated with BMD (P CONCLUSIONS: The associations between diagnostic measures of sarcopenia and BMD as an example of muscle-related outcome vary widely. Differences between diagnostic measures should be taken into account when studying sarcopenia.

Back pain episodes are traditionally regarded as individual events, but this model is currently being challenged in favour of treating back pain as a long-term or lifelong condition. Back pain can be present throughout life, from childhood to older age, and evidence is mounting that pain experience is maintained over long periods: for example, people with pain continue to have it on and off for years, and people without pain do not suddenly develop long-term pain. A number of factors predict back pain presence in epidemiological studies, and these are often present, and predictive, at different life stages. There are also factors present at particular life stages, such as childhood or adolescence, which predict back pain in adulthood. However, there are little published data on long-term pain patterns or predictors over the life course. Such studies could improve our understanding of the development and fluctuations in back pain, and therefore influence treatment approaches.

Objective To assess whether sensorimotor peripheral nerve function is associated with muscle power in community-dwelling older men. Design Longitudinal cohort study with 2.3±0.3 years of follow-up. Setting One clinical site. Participants Participants (n=372; mean age ± SD, 77.2±5.1y; 99.5% white; body mass index, 27.9±3.7kg/m 2; power, 1.88±0.6W/kg) at 1 site of the Osteoporotic Fractures in Men Study (N=5994). Interventions Not applicable. Main Outcome Measures A nerve function ancillary study was performed 4.6±0.4 years after baseline. Muscle power was measured using a power rig. Peroneal motor nerve conduction amplitude, distal motor latency, and mean f-wave latency were measured. Sensory nerve function was assessed using 10-g and 1.4-g monofilaments and sural sensory nerve conduction amplitude and distal latency. Peripheral neuropathy symptoms at the leg and feet were assessed by self-report. Results After adjustments for age, height, and total body lean and fat mass, 1 SD lower motor (β=-.07, P

Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and older human subjects subsequent to 2 weeks of immobility-induced muscle atrophy. Retraining consisted of 4 weeks of supervised resistive exercise in 9 older (OM: mean age) 67.3, range 61-74 yrs) and 11 young (YM: mean age 24.4, range 21-30 yrs) males. Measures of myofibre area (MFA), Pax7-positive satellite cells (SCs) associated with type I and type II muscle fibres, as well as gene expression analysis of key growth and transcription factors associated with local skeletal muscle milieu, were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of retraining. OM demonstrated no detectable gains in MFA (vastus lateralis muscle) and no increases in number of Pax7-positive SCs following 4wks retraining, whereas YM increased their MFA (P < 0.05), number of Pax7-positive cells, and had more Pax7-positive cells per type II fibre than OM at +3d and +4wks (P < 0.05). No age-related differences were observed in mRNA expression of IGF-1Ea, MGF, MyoD1 and HGF with retraining, whereas myostatin expression levels were more down-regulated in YM compared to OM at +3d (P < 0.05). In conclusion, the diminished muscle re-growth after immobilisation in elderly humans was associated with a lesser response in satellite cell proliferation in combination with an age-specific regulation of myostatin. In contrast, expression of local growth factors did not seem to explain the age-related difference in muscle mass recovery.

Total or near-total loss of insulin-producing β-cells occurs in type 1 diabetes. Restoration of insulin production in type 1 diabetes is thus a major medical challenge. We previously observed in mice in which β-cells are completely ablated that the pancreas reconstitutes new insulin-producing cells in the absence of autoimmunity. The process involves the contribution of islet non-β-cells; specifically, glucagon-producing α-cells begin producing insulin by a process of reprogramming (transdifferentiation) without proliferation. Here we show the influence of age on β-cell reconstitution from heterologous islet cells after near-total β-cell loss in mice. We found that senescence does not alter α-cell plasticity: α-cells can reprogram to produce insulin from puberty through to adulthood, and also in aged individuals, even a long time after β-cell loss. In contrast, before puberty there is no detectable α-cell conversion, although β-cell reconstitution after injury is more efficient, always leading to diabetes recovery. This process occurs through a newly discovered mechanism: the spontaneous en masse reprogramming of somatostatin-producing δ-cells. The juveniles display 'somatostatin-to-insulin' δ-cell conversion, involving dedifferentiation, proliferation and re-expression of islet developmental regulators. This juvenile adaptability relies, at least in part, upon the combined action of FoxO1 and downstream effectors. Restoration of insulin producing-cells from non-β-cell origins is thus enabled throughout life via δ- or α-cell spontaneous reprogramming. A landscape with multiple intra-islet cell interconversion events is emerging, offering new perspectives for therapy.

Patients over the age of 65 are the fastest growing segment of the population, and it is estimated that it comprises 12.5% of the entire population in the developed countries. Advances in medicine, science and healthy lifestyles have promoted substantially increased lifespans, as well as better quality of life with more physical activity. On the other hand, aging is associated with a variety of physiologic changes that affect orthopedic care. Due to natural involution processes older adults may not have the physiologic reserves necessary to promote healing or to prevent or recover from complications. Degenerative diseases and injuries sustained from trauma in combination with physiologic changes and comorbidity in the aged pose a significant health problem in older adults and a major treatment challenge for an orthopaedic surgeon. This review summarizes some of these unique challenges in care for older orthopaedic patient.

WOS: 000321476400010, Introduction: The objective of this study is to investigate effects of testing time and emotional valence of words on implicit and explicit memory in young and elderly individuals. Materials and Method: After valence words were presented to 240 subjects composed of adolescents (11-14), early adults (25-25) and elderly people (65 and above) performance of word stem completion and free recall were tested. Results: Main effects of the age, testing time and valence of words on implicit and explicit memory were significant. While the dual effects of age and valence; testing time and valence were found significant in implicit memory, the dual effects of testing time and age; testing time and valence were also significant in explicit memory. Moreover, the triad effects of these variables on explicit memory were also found significant. Conclusion: Performance of explicit and implicit memory, in other words conscious and inconscious retrieval declines with aging. Emotional content affects explicit and implicit memory in all ages and positive stimulations are retrieved better. The increase in performance of implicit memory brought about by positive words in all groups was interpreted as inclination of the memory inconsciously towards positive words showing a "positivity effect".

Introduction: The objective of this study is to investigate effects of testing time and emotional valence of words on implicit and explicit memory in young and elderly individuals. Materials and Method: After valence words were presented to 240 subjects composed of adolescents (11-14), early adults (25-25) and elderly people (65 and above) performance of word stem completion and free recall were tested. Results: Main effects of the age, testing time and valence of words on implicit and explicit memory were significant. While the dual effects of age and valence; testing time and valence were found significant in implicit memory, the dual effects of testing time and age; testing time and valence were also significant in explicit memory. Moreover, the triad effects of these variables on explicit memory were also found significant. Conclusion: Performance of explicit and implicit memory, in other words conscious and inconscious retrieval declines with aging. Emotional content affects explicit and implicit memory in all ages and positive stimulations are retrieved better. The increase in performance of implicit memory brought about by positive words in all groups was interpreted as inclination of the memory inconsciously towards positive words showing a "positivity effect"., Sayar, F.; Cumhuriyet Üniversitesi Psikoloji, Sivas, Turkey; email: filiz1976sayar@yahoo.com

Within the European multi-centre MyoAge project, one workpackage was designed to investigate the contribution of age-related changes to muscle mass, contractile characteristics and neural control in relation to reductions in mobility in older age. The methodology has been described here. Test centres were located in Manchester, UK; Paris, France; Leiden, The Netherlands; Tartu, Estonia and Jyväskylä, Finland. In total, 182 young (18-30 years old, 52.2 % female) and 322 older adults (69-81 years old, 50 % female) have been examined. The participants were independent living, socially active and free from disease that impaired mobility levels. The older participants were selected based on physical activity levels, such that half exceeded current recommended physical activity levels and the other half had lower physical activity levels than is recommended to maintain health. Measurements consisted of blood pressure; anthropometry and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging); lung function; standing balance and cognitive function (CANTAB). Mobility was assessed using the Timed Up and Go, a 6 min walk, activity questionnaires and accelerometers to monitor habitual daily activities. Muscle strength, power, fatigue and neural activation were assessed using a combination of voluntary and electrically stimulated contractions. Fasting blood samples and skeletal muscle biopsies were collected for detailed examination of cell and molecular differences between young and older individuals. The results from this study will provide a detailed insight into "normal, healthy" ageing, linking whole-body function to the structure and function of the neuromuscular system and the molecular characteristics of skeletal muscle.

Summary American mink (Neovison vison) kits are born altricial and fully dependent 40 on maternal care, for which the kits' vocalisations appear essential. We used Auditory Brainstem Recording (ABR) to determine (1) hearing sensitivity of adult females from two breeding lines known to differ in maternal behaviour and (2) development of hearing in kits 8-52 days of age. We also studied sound production in 20 kits throughout postnatal days 1 to 44. Adult female mink had a broad hearing range from 1 kHz to above 70 kHz, with peak sensitivity (threshold of 20 dB SPL) at 8-10 kHz, and no difference in sensitivity between the two breeding lines (P>0.22) to explain the difference in maternal care. Mink kits showed no signs of hearing up to postnatal day 24. From day 30 all kits had ABRs indicative of hearing. Hearing sensitivity increased with age, but was still below the adult level at postnatal day 52. When separated from their mothers kits vocalized loudly. Until age 22 days, 90% of all kits vocalized with no significant decline with age (P=0.27). From day 25, concurrent with the start of hearing, the number of vocalizing kits decreased with age (P

Background Among the many definitions of frailty, the frailty phenotype defined by Fried et al. is one of few constructs that has been repeatedly validated: first in the Cardiovascular Health Study (CHS) and subsequently in other large cohorts in the North America. In Europe, the Survey of Health, Aging and Retirement in Europe (SHARE) is a gold mine of individual, economic and health information that can provide insight into better understanding of frailty across diverse population settings. A recent adaptation of the original five CHS-frailty criteria was proposed to make use of SHARE data and measure frailty in the European population. To test the validity of the SHARE operationalized frailty phenotype, this study aims to evaluate its prospective association with adverse health outcomes. Methods Data are from 11,015 community-dwelling men and women aged 60+ participating in wave 1 and 2 of the Survey of Health, Aging and Retirement in Europe, a population-based survey. Multivariate logistic regression analyses were used to assess the 2-year follow up effect of SHARE-operationalized frailty phenotype on the incidence of disability (disability-free at baseline) and on worsening disability and morbidity, adjusting for age, sex, income and baseline morbidity and disability. Results At 2-year follow up, frail individuals were at increased risk for: developing mobility (OR 3.07, 95% CI, 1.02-9.36), IADL (OR 5.52, 95% CI, 3.76-8.10) and BADL (OR 5.13, 95% CI, 3.53-7.44) disability; worsening mobility (OR 2.94, 95% CI, 2.19- 3.93) IADL (OR 4.43, 95% CI, 3.19-6.15) and BADL disability (OR 4.53, 95% CI, 3.14-6.54); and worsening morbidity (OR 1.77, 95% CI, 1.35-2.32). These associations were significant even among the prefrail, but with a lower magnitude of effect. Conclusions The SHARE-operationalized frailty phenotype is significantly associated with all tested health outcomes independent of baseline morbidity and disability in community-dwelling men and women aged 60 and older living in Europe. The robustness of results validate the use of this phenotype in the SHARE survey for future research on frailty in Europe.

PURPOSE: To evaluate the association between astigmatism and idiopathic congenital nystagmus (ICN) in infantile nystagmus syndrome (INS). MATERIALS AND METHODS: We analysed refractive errors in a cohort of 488 consecutive patients with ICN (group A) and further compared the results obtained with those of 488 age-matched controls with no nystagmus (group B). Only the worst eye was considered for statistical analysis. All patients were stratified into the following age groups: 1 to 4 years (age group 1); 5 to 12 years (age group 2); and 13 years to 57 years (age group 3) (mean age: 29). RESULTS: Three hundred and seventy patients (69.7 %) in group A and 269 patients (55,12 %) in group B had refractive errors. The types of refractive errors observed were: myopia, hyperopia (>0.50 dioptres) and astigmatism (>1.25 dioptres). Results in group A were as follows: 319 patients (65.37 %) were astigmatic, 34 (6.97 %) were hyperopic, and 17 (3.48 %) were myopic. Mean right-eye astigmatism was 2.72 dioptres, and mean left-eye astigmatism was 2.69 dioptres. Results in group B were as follows: 56 (11.47 %) were astigmatic, 165 (33.81) were hyperopic, and 48 (9.84) were myopic. Mean right-eye astigmatism was 2.05 dioptres, and mean left-eye astigmatism was 2.37 dioptres. The prevalence of astigmatism is greater, in the entire sample, for subjects from age groups 2 and 3 (p

Background: Telomere length has been considered in many cross-sectional studies as a biomarker of aging. However the association between shorter telomeres with lower survival at advanced ages remains a controversial issue. This association could reflect the impact of other health conditions than a direct biological effect. Objective: To test whether leukocyte telomere length is associated with 5-year survival beyond the impact of other risk factors of mortality like comorbidity, functional, nutritional and cognitive status. Design: Prospective study. Setting and participants: A population representative sample of 444 patients (mean age 85 years; 74% female) discharged from the acute geriatric hospital of Geneva University Hospitals (January-December 2004), since then 263 (59.2%) had died (December 2009). Measurements: Telomere length in leukocytes by flow cytometry. Results: In univariate model, telomere length at baseline and cognitive status were not significantly associated with mortality even when adjusting for age (R2=9.5%) and gender (R2=1.9%). The best prognostic predictor was the geriatric index of comorbidity (GIC) (R2=8.8%; HR=3.85) followed by more dependence in instrumental (R2=5.9%; HR=3.85) and based (R2=2.3%; HR=0.84) activities of daily living and lower albumin levels (R2=1.5%; HR=0.97). Obesity (BMI>30: R2=1.6%; HR=0.55) was significantly associated with a two-fold decrease in the risk of mortality compared to BMI between 20-25. When all independent variables were entered in a full multiple Cox regression model (R2=21.4%), the GIC was the strongest risk predictor followed by the nutritional and functional variables. Conclusion: Neither telomeres length nor the presence of dementia are predictors of survival whereas the weight of multiple comorbidity conditions, nutritional and functional impairment are significantly associated with 5-year mortality in the oldest old

From the age of 50 the risk of fracture during the remaining years of life is estimated to be 40% in women and 20% men. The management of a fracture in the elderly is complex for several reasons, including decreased bone strength, a frequent association with previous joint replacement surgery or another orthopaedic implant, a high risk for anesthesia, difficulty in following postoperative recommendations, and an increased postoperative mortality. This article offers a review of fractures around the knee: distal femur, proximal tibia, patella and periprosthetic fractures. The vast majority of these fractures are treated surgically. When surgery is indicated, treatment should be initiated as soon as possible according to the patient's general condition in order to minimize the risk of complications and deconditioning.

Erken, Gülten (Balikesir Author), The harmful effects of aging on blood rheology have been well known. These effects in the aging have been found to be associated with an increase in oxidative stress. The aim of this study was to seek whether treatment of vitamin E as a potent antioxidant could improve the age-related haemorheological abnormalities. For this purpose, male Wistar rats at the age of 3 and 24 months were used. The following parameters were evaluated: red blood cell (RBC) deformability, aggregation, plasma viscosity, vitamin E level, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI), and the following results were obtained. First, aging was associated with a decrease in RBC deformability and increase in RBC aggregation and plasma viscosity. Second, compared with the young group, while plasma TOS levels and OSI were found to be significantly increased in aged rats, there was no significant change in their plasma TAS level. Third, vitamin E administration produced significant improvement in RBC deformability and decrement in TOS and OSI values in aged rats with respect to young and aged control groups. We did not find any significant effect of vitamin E treatment on RBC aggregation in both young and aged rats and finally, we found a significantly lower plasma vitamin E level in aged rats than in young rats. In conclusion, these findings suggest that blood rheology impairs with age and vitamin E has ameliorating effects on age-induced haemorheological abnormalities especially in RBC deformability, probably by reducing the increased oxidative stress in old age.

OBJECTIVE: Both subclinical hypothyroidism and the metabolic syndrome have been associated with increased risk of coronary heart disease events. It is unknown whether the prevalence and incidence of metabolic syndrome is higher as TSH levels increase, or in individuals with subclinical hypothyroidism. We sought to determine the association between thyroid function and the prevalence and incidence of the metabolic syndrome in a cohort of older adults. DESIGN: Data were analysed from the Health, Ageing and Body Composition Study, a prospective cohort of 3075 community-dwelling US adults. PARTICIPANTS: Two thousand one hundred and nineteen participants with measured TSH and data on metabolic syndrome components were included in the analysis. MEASUREMENTS: TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria. RESULTS: At baseline, 684 participants met criteria for metabolic syndrome. At 6-year follow-up, incident metabolic syndrome developed in 239 individuals. In fully adjusted models, each unit increase in TSH was associated with a 3% increase in the odds of prevalent metabolic syndrome (OR, 1.03; 95% CI, 1.01-1.06; P = 0.02), and the association was stronger for TSH within the normal range (OR, 1.16; 95% CI, 1.03-1.30; P = 0.02). Subclinical hypothyroidism with a TSH > 10 mIU/l was significantly associated with increased odds of prevalent metabolic syndrome (OR, 2.3; 95% CI, 1.0-5.0; P = 0.04); the odds of incident MetS was similar (OR 2.2), but the confidence interval was wide (0.6-7.5). CONCLUSIONS: Higher TSH levels and subclinical hypothyroidism with a TSH > 10 mIU/l are associated with increased odds of prevalent but not incident metabolic syndrome.

Spontaneous waves of bursts of action potentials propagate across the ganglion-cell surface of developing retinas. A recent biophysical model postulated that this propagation is mediated by an increase in extracellular K+, following its ejection from ganglion cells during action potentials. Moreover, the model hypothesized that bursts might terminate due to the accumulation of intracellular Ca2+ and the subsequent activation of a Ca(2+)-dependent K+ conductance in the cells' dendrites. Finally, the model proposed that an excitatory synaptic drive causes a neuromodulation of the waves' properties. To test the feasibility of the model, we performed computer simulations of the network of developing ganglion cells under control and pharmacological-manipulation conditions. In particular, we simulated the effects of neostigmine, Cs+ and TEA, low Ca2+ concentrations, and Co2+. A comparison of the simulations with electrophysiological and pharmacological experimental data recently obtained in turtles (Sernagor and Grzywacz, 1993a), and cats and ferrets (Meister et al., 1991; Wong et al., 1993), showed that the model for the most part is consistent with the behavior of developing retinas. Moreover, modifications of the model to allow for GABAergic inputs onto ganglion cells (Sernagor and Grzywacz, 1994) and poor [K+]out buffering (Connors et al., 1982) improved the model's fits. These results lent further support to important roles of extracellular K+ concentration and synaptic drive for the propagation of waves.

While the capacity of O-2A oligodendrocyte progenitors to migrate in cell culture and during in vivo myelin formation is well documented, little is known about factors that regulate the motility of these cells. Here, we report on an in vitro model that allowed us to evaluate the contribution of alpha 2–8 linked polysialic acid (PSA) to O-2A cell motility. Using explant cultures of newborn rat neurohypophysis, we observed that individual glial fibrillary acidic protein (GFAP)- positive cells rapidly disperse from the explants, and that cells of the O-2A lineage predominate in the migratory cell pool. Presumed O-2A progenitor cells had a round or bipolar morphology and presented both A2B5 and GFAP immunoreactivity. When cultured in medium containing 10% fetal calf serum, these cells differentiated into stellate-shaped, A2B5/GFAP-positive type 2 astrocytes. In serum-free medium most of them developed into O4/galactocerebroside-positive oligodendrocytes. O-2A lineage cells were found only in a specific developmental period extending from embryonic day 21 to postnatal day 3. A monoclonal antibody, which recognizes the alpha 2–8 linked PSA, characteristic of the embryonic form of NCAM, revealed immunoreactivity on the surface of O-2A progenitor cells, whereas mature oligodendrocytes, type 2, type 1 astrocytes as well as flat GFAP-negative cells were negative. Treatment of the explants with endoneuraminidase purified from phage K1, which specifically removes PSA from the surface of the cell, resulted in a complete blockade of the dispersion of O-2A lineage population from the explant. The effects of the enzymatic treatment were both selective and reversible: migration of GFAP-negative fibroblast-like cells that are normally PSA negative was not influenced, and upon removal of the enzyme, cells of the O-2A lineage were readily detectable in the migrating population. These results provide direct evidence that alpha 2–8 linked PSA contribute to the motility of O-2A, glial progenitor cells.

The potential for development of biomedical technologies capable of extending the human lifespan raises at least two kinds of question that it is important both to distinguish and to connect with one another: scientific, factual questions regarding the feasibility of life extension interventions; and questions concerning the ethical issues related to the extension of life- and healthspans. This paper provides an account of some life extension interventions considered to be amongst the most promising, and presents the ethical questions raised by the prospect of their pursuit. It is suggested that problems concerning the effects of these technologies on health care resources and on intergenerational relationships will be the most difficult to tackle.

OBJECTIVES: To compare the use of co-medication, the potential drug-drug interactions (PDDIs) and the effect on antiretroviral therapy (ART) tolerability and efficacy in HIV-infected individuals according to age, ≥ 50 years or

Starenje uzrokuje brojne tjelesne i psihološke promjene koje mogu utjecati na nutritivne potrebe i nutritivni status. Prisutnost kroničnih bolesti i uzimanje lijekova mogu uzrokovati neravnotežu između potrebe za nutrijentima i prehrambenog unosa, što vodi nastanku malnutricije ili lošeg statusa uhranjenosti. Brojna istraživanja pokazuju da je malnutricija učestali problem među osobama starije dobi. Stoga redovita procjena nutritivnog statusa čini bitan dio zdravstvene skrbi za osobe starije dobi. Pritom je važno uzeti u obzir odrednice geroantropometrije. Fiziološke promjene vezane uz starenje utječu na potrebe za nutrijentima. Energetske potrebe i potrebe za makronutrijentima smanjuju se, međutim potrebe za mikronutrijentima jednake su ili veće nego tijekom zrele dobi. Dodatno, brojne psihosocijalne i socioekonomske promjene koje prate starenje mogu utjecati na prehrambeni unos. Planiranje obroka važan je dio nutritivne njege osoba starije dobi, a veoma važni mogu biti i dodaci prehrani te oralni nutritivni dodaci (enteralni pripravci) koji se propisuju kod dijagnosticirane ili prijeteće malnutricije. Radna skupina koju su činili internisti, gerontolozi, antropolozi, nutricionisti i ostali stručnjaci, posebno upućeni u liječenje gerijatrijskih bolesnika izradila je Hrvatske smjernice za prehranu osoba starije dobi. Izrada smjernica temeljena je na dokazima iz relevantne medicinske literature te kliničkim iskustvima članova radne skupine., Aging produces numerous physical and physiologic changes, which in turn alter nutritional requirements and affect nutritional status. The presence of chronic disease, and/or medications can enhance potential disparities between nutrient needs and dietary intake, leading to malnutrition. Indeed, research suggests that malnutrition is a common condition among the elderly. Therefore, regular nutritional assessment should be done as an integral part of healthcare for elderly. Also, it is important to take in consideration all determinants of geroanthropometry. The physiologic changes associated with aging affect requirement for several essential nutrients. In general, the requirement for many nutrients decreases, concomitant with the decrease in energy needs. However, some nutrients are needed in higher amounts. Additionally, various psychosocial and socioeconomic changes that often attend aging may also alter dietary intake. Dietary planning is important part of nutritional care in the elderly. Also, some elderly persons can benefit with dietary supplements and oral nutritional supplements (enteral formulas) which can be prescribed by diagnosed or threatening malnutrition. Croatian guidelines for nutrition in the elderly have been developed by interdisciplinary expert group of Croatian clinicians, gerontologists, anthropologists, nutritionists and other professionals involved with care for elderly population. The guidelines are based on evidence from relevant medical literature and clinical experience of working group.

Age-related changes of body composition affect health status. This study aims at clarifying body composition changes in healthy elderly subjects, and evaluating the impact of physical activity on these changes.In 1999, 213 subjects ≥ 65 years recruited through advertisements underwent assessment of health state, energy expenditure by physical activity, body composition by bioimpedance analysis and body cell mass by total body potassium. In 2008, 112 of them repeated these assessments with additional determination of Barthel index, Mini Mental State Examination and Geriatric Depression Score.Lean tissues decreased in both genders (p 0.05). Compared to subjects aged 65-74 years at baseline, those aged ≥75 years lost more body weight (men: -3.7 ± 5.4 vs. 0.4 ± 5.4 kg, women: -3.6 ± 5.5 vs. 0.3 ± 5.2 kg, both p 0.05), and fat-free mass (men: -3.6 ± 3.3 vs. -0.4 ± 2.7 kg, women: -1.8 ± 2.3 vs. -0.1 ± 2.5 kg, both p 0.05). Plotting of fat-free mass evolution against age at baseline showed an exponential loss of fat-free mass. Increased physical activity limited lean tissue loss in men but not in women.Loss of lean tissues occurs exponentially with aging. Further research should confirm these changes in subjects over 80 years. Increasing physical activity limits fat-free mass loss in men but not women.

Our objective was to assess the effects of an 8-week exercise training program with a special focus on light- to moderate-intensity resistance exercises (30-70% of one repetition maximum, 1RM) and a subsequent 4-week training cessation period (detraining) on muscle strength and functional capacity in participants aged 90 and older. We studied a randomized controlled trial performed during March to September 2009. Forty nonagenarians (90-97) were randomly assigned to an intervention or control group (16 women and 4 men per group). We analyzed eight-week muscle strength exercise intervention focused on lower limb strength exercises of light to moderate intensity. we studied handgrip strength, 8-m walk test, 4-step stairs test, Timed Up and Go test, and number of falls. A significant group by time interaction effect (P=.02) was observed only for the 1RM leg press. In the intervention group, 1RM leg press increased significantly with training by 10.6 kg [95% confidence interval (CI)=4.1-17.1 kg; P=.01]. Except for the mean group number of falls, which were 1.2 falls fewer per participant in the intervention group (95% CI=0.0-3.0; P=.03), no significant training effect on the secondary outcome measures was found. In conclusion, exercise training, even of short duration and light to moderate intensity, can increase muscle strength while decreasing fall risk in nonagenarians. 3.737 JCR (2011) Q1, 9745 Geriatrics & gerontology UEM

In humans, the erect position and bipedal walk is possible because of a balance between pelvic and spinal parameters. The most important pelvic parameter is the pelvic incidence which represents the base on which the spine lies. With aging, thoracic kyphosis increases, lumbar lordosis decreases, compromising the spino-pelvic balance. Compensatory phenomenons are possible, but rely mostly on the amplitude of pelvic incidence. Analysis of spino-pelvic parameters and detection of a compensated or uncompensated sagittal imbalance are mandatory before any therapeutic action is undertaken for a degenerative pathology of the spine.

We developed several techniques that provide data on body elemental composition from in vivo measurements in rats. These methods include total body potassium by whole-body counting of endogenous 40K; total body calcium (TBCa), sodium and chloride by in vivo neutron activation analysis and total body phosphorus (TBP) and nitrogen (TBN) by photon activation analysis. These elements provide information on total body fat, total body protein and skeletal mass. Measurements were made in 6-, 12- and 24-month-old rats. TBN increased slightly between 6 and 12 months but was significantly lower by 24 months, indicating a substantial loss in total body protein. Working at the National Synchrotron Light Source, we studied rat femurs by computed microtomography (CMT), and the elemental profile of the femur cortex by synchrotron-radiation induced X-ray emission (SRIXE). Although there were no significant changes in TBCa and TBP, indices of skeletal mass, CMT revealed a marked increase in the size and number of cavities in the endosteal region of the femur cortex with increasing age. The SRIXE analysis of this cortical bone revealed a parallel decrease in the endosteal Ca/P ratio. Thus, there are major alterations in bone morphology and regional elemental composition despite only modest changes in total skeletal mass. J Nutr

Age related macular degeneration (ARMD) is a disease of old people with chronic evolution causing legal blindness. Clinically is classified as: atrophic or dry form and the wet form. Histopathologically the atrophic form is characterized by increased choriocapillaris wall thickness with partial or total lumen obliteration, retinal pigmented epithelium atrophy and hard drusen. In the wet form the most important feature is the neovascular proliferation in the retinal layer, hemorrhage, soft drusen and at ending stage disciform scar in the subretinal space. Angiogenic factors have been admitted in the etiology of ARMD and recently antiangiogenic drugs are used as treatment. Univ Fed Minas Gerais, Fac Med, Belo Horizonte, MG, Brazil Univ Fed Sao Paulo, Sao Paulo, Brazil Univ Fed Sao Paulo, Sao Paulo, Brazil Web of Science

The lithium–pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium–pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24 h of SE), the latent phase, and the early and late chronic phases. During SE, GLUT1 expression was increased throughout the brain between 1 and 12 h of SE, more strongly in adult rats; GLUT3 increased only transiently, at 1 and 4 h of SE and mainly in PN10 rats; MCT1 was increased at all ages but 5-10-fold more in adult than in immature rats; MCT2 expression increased mainly in adult rats. At all ages, MCT1 and MCT2 up-regulation was limited to the circuit of seizures while GLUT1 and GLUT3 changes were more widespread. During the latent and chronic phases, the expression of nutrient transporters was normal in PN10 rats. In PN21 rats, GLUT1 was up-regulated in all brain regions. In contrast, in adult rats GLUT1 expression was down-regulated in the piriform cortex, hilus and CA1 as a result of extensive neuronal death. The changes in nutrient transporter expression reported here further support previous findings in other experimental models demonstrating rapid transcriptional responses to marked changes in cerebral energetic/glucose demand.

PURPOSE: The purpose of the study was to assess the effect of cigarette smoking on indicators of bone strength across a wide age range, controlling for physical activity and neuromuscular performance.METHODS: We conducted a cross-sectional study with 41 smokers (mean age +/- SD, 41.0 +/- 16.1 yr) and 53 nonsmokers (47.5 +/- 18.2 yr) of both sexes. Bone strength indicators (BSI) were assessed in the lower leg and forearm by peripheral quantitative computed tomography along with physical activity, muscle cross-sectional area, and maximal voluntary muscle force.RESULTS: Physical activity level and muscle cross-sectional area of the leg and arm were similar in smokers and nonsmokers. Although trabecular volumetric bone mineral density and epiphyseal bone mineral content, both indicators of BSI, decreased with age in the nonsmokers' tibia (P < 0.001), this was not observed in the smokers (interaction age x smoking: P = 0.014 and P = 0.032 for density and content, respectively). Regression coefficients were nonsignificant in nonsmokers, whereas coefficients in smokers were -1.24 mg/cm x yr [95% confidence interval (CI) = -2.16-0.33; P = 0.01] for content and -1.20 mg/cm(3) x yr (95% CI = -1.76-0.62; P < 0.001) for trabecular density. The BSI values in the smokers were independent of their smoking history (r(2) = 0.000-0.021), and no effects of sex were observed in the smoking-related differences in BSI.CONCLUSIONS: Smoking compromises bone strength by diaphyseal marrow cavity expansion and epiphyseal trabecular bone content reductions. These effects seem to wane with age. The causes of the attenuated effect of smoking on bone at old age remain enigmatic but might be linked to an interaction between the smoke-related factors and senescence processes affecting bone.

Yawning is a phylogenetically old behaviour that can be observed in most vertebrate species from foetal stages to old age. The origin and function of this conspicuous phenomenon have been subject to speculations for centuries. Here, we review the experimental evidence for each of these hypotheses. It is found that theories ascribing a physiological role to yawning (such as the respiratory, arousal, or thermoregulation hypotheses) lack evidence. Conversely, the notion that yawning has a communicative function involved in the transmission of drowsiness, boredom, or mild psychological stress receives increasing support from research in different fields. In humans and some other mammals, yawning is part of the action repertoire of advanced empathic and social skills.

Human aging and longevity are complex and multi-factorial traits that result from a combination of environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype. The multi-factorial process of aging acts at different levels of complexity, from molecule to cell, from organ to organ systems and finally to organism, giving rise to the dynamic "aging mosaic". At present, an increasing amount of experimental data on genetics, genomics, proteomics and other -omics are available thanks to new high-throughput technologies but a comprehensive model for the study of human aging and longevity is still lacking. Systems biology represents a strategy to integrate and quantify the existing knowledge from different sources into predictive models, to be later tested and then implemented with new experimental data for validation and refinement in a recursive process. The ultimate goal is to compact the new acquired knowledge into a single picture, ideally able to characterize the phenotype at systemic/organism level. In this review we will briefly discuss the aging phenotype in a systems biology perspective, showing four specific examples at different levels of complexity, from a systemic process (inflammation) to a cascade-process pathways (coagulation) and from cellular organelle (proteasome) to single gene-network (PON-1), which could also represent targets for anti-aging strategies.

PURPOSE: The purpose of this study is to determine gender-specific differences in the development of necrosis in persistent ischemic tissue and to analyze whether differences are due to gender-specific loss of vascular reactivity or change in ischemic tolerance. METHODS: Hairless mice (skh-1) of both genders were assigned to three groups of adolescent, adult, and senescent age. Critical ischemia was induced by transection of the two distal pedicles of the animal's ear. Microcirculation was assessed over a 5-day period using intravital epifluorescence microscopy. Tissue necrosis, blood flow, functional capillary density (FCD), red blood cell (RBC) velocity, and capillary diameter were analyzed. RESULTS: Induction of persistent ischemia caused an age-dependent demarcation of nonperfused flap tissue. Adult and senescent females developed markedly more necrosis than age-matched males (49 +/-1% vs. 37 +/-3% and 53 +/- 3% vs. 44 +/- 2%, respectively; p

It has been reported in the literature that executive functions may be fractioned into updating, shifting, and inhibition. The present study aimed to explore whether these executive sub-components can be identified in a more age-heterogeneous sample and see if they are prone to an age-related decline. We tested the performances of 81 individuals aged from 18 to 88 years old in each executive sub-component, working memory, fluid intelligence and processing speed. Correlation analysis revealed only a slight positive relationship between the two updating measures. A linear decrement with age was observed only for two complex executive tests. Tasks indexing working memory, processing speed and fluid intelligence showed a stronger linear decline with age than executive tasks. In conclusion, our results did not replicate the executive structure known from the literature, and revealed that decrement in executive function is not an unavoidable concomitant of aging but rather concerns specific executive tasks.

The objective of this study was to systematically review all published articles examining the relationship between the occurrence of falls and changes in gait and attention-demanding task performance whilst dual tasking amongst older adults. An English and French Medline and Cochrane library search ranging from 1997 to 2008 indexed under 'accidental falls', 'aged OR aged, 80 and over', 'dual task', 'dual tasking', 'gait', 'walking', 'fall' and 'falling' was performed. Of 121 selected studies, fifteen met the selection criteria and were included in the final analysis. The fall rate ranged from 11.1% to 50.0% in retrospective studies and from 21.3% to 42.3% in prospective ones. Amongst the three retrospective and eight prospective studies, two and six studies, respectively, showed a significant relationship between changes in gait performance under dual task and history of falls. The predictive value for falling was particularly efficient amongst frail older adults compared with healthy subjects. Two prospective studies challenged the usefulness of the dual-task paradigm as a significant predictor compared to single task performance and three studies even reported that gait changes whilst dual tasking did not predict falls. The pooled odds ratio for falling was 5.3 (95% CI, 3.1-9.1) when subjects had changes in gait or attention-demanding task performance whilst dual tasking. Despite conflicting early reports, changes in performance whilst dual tasking were significantly associated with an increased risk for falling amongst older adults and frail older adults in particular. Description of health status, standardization of test methodology, increase of sample size and longer follow-up intervals will certainly improve the predictive value of dual-task-based fall risk assessment tests.

The aim of this study was to compare the performance of elderly and young participants on a series of memory tasks involving either intentional or unintentional inhibitory control of memory content. Intentional inhibition processes in working and episodic memory were explored with directed forgetting tasks and in semantic memory with the Hayling task. Unintentional inhibitory processes in working memory, long-term memory, and semantic memory were explored with an interference resolution task, the retrieval practice paradigm, and the flanker task, respectively. The results indicate that elderly participants' performance on the two directed forgetting tasks and the Hayling task is lower than that of young ones, and that this impairment is not related to their initial memory capacity. This suggests that there is a specific dysfunction affecting intentional inhibitory control of memory contents in normal ageing.

Normal human fibroblasts have a limited replicative potential in culture and eventually reach a state of irreversible growth arrest, termed senescence. In a previous study aiming to identify genes that are differentially regulated during cellular senescence we have cloned clusterin/apolipoprotein J (Apo J), a 80 kDa secreted glycoprotein. In the current report we pursue our studies and show that senescence of human diploid fibroblasts is accompanied by up-regulation of both Apo J mRNA and protein levels, but with no altered biogenesis, binding partner profile or intracellular distribution of the two Apo J forms detected. To analyze the causal relationship between senescence and Apo J protein accumulation, we stably overexpressed the Apo J gene in primary as well as in SV40 T antigen-immortalized human fibroblasts and we showed no alteration of the proliferative capacity of the transduced cells. Despite previous reports on tumor-derived cell lines, overexpression of Apo J in human fibroblasts did not provide protection against apoptosis or growth arrest induced by hydrogen peroxide. Overall, our results suggest that Apo J overexpression does not induce senescence but it is rather a secondary consequence of the senescence phenotype. To our knowledge this is the first report that provides a functional analysis of human Apo J during replicative senescence. FEBS Lett

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling. Mice lacking ß-adrenergic receptors have increased body weight, bone mineral density, and bone turnover versus controls, but are not protected from bone loss due to deficiency of estrogens..

Colouration may either reflect a discrete polymorphism potentially related to life-history strategies, a continuous signal related to individual quality or a combination of both. Recently, Vercken et al. [J. Evol. Biol. (2007) 221] proposed three discrete ventral colour morphs in female common lizards, Lacerta vivipara, and suggested that they reflect alternative reproductive strategies. Here, we provide a quantitative assessment of the phenotypic distribution and determinants of the proposed colour polymorphism. Based on reflectance spectra, we found no evidence for three distinct visual colour classes, but observed continuous variation in colour from pale yellow to orange. Based on a 2-year experiment, we also provide evidence for reversible colour plasticity in response to a manipulation of the adult population sex ratio; yet, a significant portion of the colour variation was invariant throughout an adult female's life. Our results are thus in agreement with continuous colour variation in adults determined by environmental factors and potentially also by genetic factors.

The effects of aging and gender on balance performance (BP) among ambulatory adults were investigated in the current work. If there was a relation between the BP and a history of falling, this was also detected. Two hundred and forty ambulatory subjects were divided into two groups depending on their age: (1) 125 middle-aged subjects (50-64 years); (2) 115 elderly subjects (65-75). The functional reach (FR) test, the timed up and go (TUG) test, the sit to stand (STS) test and the step test (ST) were used to evaluate the BP. The fall rate (1-2 in the last year) was 8% for the middle-aged group and was 13.9% for the elderly group. Middle-aged adults had better scores on all tests in comparison to the elderly people. There have been differences found between genders regarding the BP in both groups, except the FR scores in the middle-aged group. The FR distance of the faller subjects was rather low in comparison to non-faller elderly subjects. However, there were no significant differences between the faller and non-faller subjects in both groups regarding other tests' scores. The results of this study indicate that aging affects the BP year by year. The information in this paper can provide normative data to be used as a comparison to clinically obtained information.