Ageing Research

From aging to cancer: a DNA methylation journey

Natalia Puig — 2012-02-15

Epigenetic gene silencing through DNA promoter hypermethylation is now recognised as a major step in the neoplastic transformation of the cell. The methylation levels of several genes increase with age in normal tissues such as the prostate or colon. Genes like WRN or LMNA that are involved in progeria,a premature aging disease WRN and LMNA, are epigenetically inactivated in cancer. In both aging and cancer, global DNA methylation decreases, potentially accounting for the characteristic genomic instability of these processes. In this review, we will focus on how the accumulation of changes in DNA methylation during aging impact tumourigenesis.

Physical activity and brain plasticity in late adulthood: a conceptual and comprehensive review

Kirk I. Erickson — 2012-03-06

A growing body of evidence from neuroscience, epidemiology, and kinesiology suggests that physical activity is effective as both a prevention and treatment for cognitive problems throughout the lifespan. Given the expected increase in the proportion of older adults in most countries over the next 40 years, physical activity could be a low-cost and relatively accessible method for maintaining cognitive function throughout later life. Despite the emerging recognition of physical activity as a powerful method to enhance brain health, there is continued confusion from both the public and scientific communities about what the extant research has discovered about the potential for physical activity to improve neurocognitive health and which questions remain unanswered. In this review, we outline four overarching themes that provide a conceptual structure for understanding the questions that have been asked and have been addressed, as well as those that have yet to be answered. These themes are descriptive, mechanistic, applied, and moderating questions. We conclude from our review that descriptive questions have been the first and most thoroughly studied, but we have much yet to learn about the underlying mechanisms, application, and moderating factors that explain how and to what extent physical activity improves brain health.

Hypoxia-inducible factor 1-alpha target protein up-regulation in Hypoxic cochlear neurons is associate with aged-related hearing loss in C57BL/6 mice

Emilie Donadieu — 2012-01-18

Molecular mechanisms underlining hypoxia- induced aged-hearing loss were studied. 3- months C57BL/6 mice were subjected to four weeks of hypoxia (10% 02), whereas, controls were kept under normoxic condition for up to six months. Auditory function was explored by CAP and Preyer’s reflex measurements and correlated with histological analysis of the cochlea. The presence of oxidative damage, HIF-1 responsive target genes regulation involved in cell death, inflammation and neovascularization were assessed by immunofluorescence analysis. Hypoxia was associated to severe hearing loss at 4-8 and 16 KHz and degeneration of the cochlea, with significant cell loss (30%) in the spiral ganglion, the lateral wall, and the hair cells with a basal-apical alteration gradient. This was correlated with ROS formation and HIF-1a overexpression. Cochlear degeneration was due to apoptosis via activated caspase-3, P53, Bax and Bcl-2 protein differential expression in spiral ganglion, modiolus and spiral ligament. On the other hand, Hsp70, NF-kB transcription factor pathway and inflammatory mediators (caspase-1 and TNF-a) were induced in the stria vascularis. Furthermore, a phenomenon of neovascularization was observed with significant thickening of stria vascularis and increased expression of VEGF. In total, we demonstrated that the tandem-HIF-ROS is responsible for the caspase-3 and Bax–mediated apoptosis via P53 protein accumulation in the cochlear neurons, while inflammatory response mediated by Hsp70 stress protein and NF-kB transcription factor generating a neovascularization phenomenon occurred in stria vascularis.

Relations between cognitive status and medication adherence in patients treated for memory disorders

Raymond L. Ownby — 2012-01-09

Medication adherence has been increasingly recognized as an important factor in elderly persons’ health. Various studies have shown that medication non-adherence is associated with poor health status in this population. As part of a study of the effects of two interventions to promote medication adherence in patients treated for memory problems, information on medication adherence and cognitive status was collected at 3-month intervals. Twenty-seven participants (16 men, 11 women, age 71-92 years) were assigned to control or treatment conditions and adherence was evaluated with an electronic monitoring device. Cognitive status was evaluated at 3- month intervals beginning in April of 2003 and continuing through September of 2006. We have previously reported on the effectiveness of these interventions to promote adherence. In this paper, we examine the relations of cognitive status and adherence over time using a partial least squares path model in order to evaluate the extent to which adherence to cholinesterase medications was related to cognitive status. Adherence predicted cognitive status at later time points while cognition did not, in general, predict adherence. Results thus suggest that interventions to ensure high levels of medication adherence may be important for maintaining cognitive function in affected elderly people.

Skilling up for training: a feasibility study investigating acute effects of stochastic resonance whole-body vibration on postural control of older adults

Slavko Rogan — 2012-03-07

The present pilot study investigated the feasibility of applying a single bout stochastic resonance whole-body vibration in deconditioned elderly individuals and the effects on static and dynamic balance and reaction time. We report the results of a non-blinded randomized control trial with a pre-test/post-test design. Twenty elderly individuals were randomized into either single bout stochastic resonance whole-body vibration (SR-WBV) (n=10, frequency 5 Hz, Noise 4) or control (n=10). SR-WBV received 5 sets of 1 min stochastic whole-body vibration (5 Hz, Noise 4: vibration with a randomly varying frequency, 1=low, 4=high) with 1 min rest in between. The control group rested for 10 min without any intervention. Functional reach test (FRT), semi-tandem stand (STS), Expanded Timed Get Up-and-Go Test (ETGUG), single task- (ST) and dual task walking time (DT), chair rising (CR), and foot (RTF) and hand reaction time (RTH) were measured before and after the intervention. Within- and between group differences were analyzed using repeated measures. In order to assess the meaningfulness of pre-training to post-training changes, the effect size (ES) was calculated according to Cohen’s d. All participants in the study accepted and adhered to the WBV session and performed scheduled follow-up measurements. There were no adverse events. Change values for dynamic balance showed a strong trend towards improvement for FRT of about 4.5% (ES=0.52, P=0.161). Change values for RTF (5.9%; ES=0.55; P =0.169) showed a trend towards improvement in the SR-WBV only. The results suggest that stochastic resonance WBV is both safe and well accepted by elderly individuals in assisted living institutions, and might have beneficial effects on balance in these adults. Further research is warranted to determine whether this device might be of use in the skilling-up phase of an exercise program when training is initiated in strongly deconditioned and/or frail elderly. The new training protocol is expected to allow for safe skilling-up training of deconditioned older adults in assisted living institutions.

Quality of life of older Chilean subjects living in metropolitan Santiago, Chile. Influence of socioeconomic status

Daniel Bunout — 2011-12-20

Quality of life (QOL) of older people is becoming an important public health concern and should be evaluated. The aim of this study was to evaluate socioeconomic and individual determinants of QOL of older subjects living in metropolitan Santiago, Chile. We first carried out a qualitative phase with focus groups of older people. According to the conclusions of the focus groups, a questionnaire about QOL was devised and added to the WhoQoL (World Health Organization Quality of Life) and WHOQoL-Old brief questionnarires. The final document with 85 questions was applied to healthy older subjects living in the community. A total of 1,676 subjects aged 71.8±7.4 years (1,189 women) took part in the survey. A multiple stepwise regression model showed that a higher socioeconomic level, a better educational level, performing voluntary work, having a partner, participating in groups with other older people, and being younger were factors independently associated with a higher QOL. A principal components analysis showed that psychological health and social relationships were the main domains that explained the total quality of life score. Psychological health and social relationships were the main determinants of QOL in this sample of older Chilean people living in metropolitan Santiago.

Age-related deficits of manual grasping in a laboratory versus in an everyday-like setting

Otmar Bock — 2012-05-09

This study compared the grasping performance of 24 younger (20-30 years of age) and 24 older subjects (60-70 years of age) in a typical laboratory task (L) where movements were repetitive, externally triggered, purposeless and attention-attracting, and in an everydaylike task (E) where movements were part of a rich behavioral repertoire, internally initiated, purposive and little attended. We registered a wide range of kinematic and force parameters, and calculated their within-subject means and variation coefficients. Multiple differences emerged between the parameter values in L and E. Factor analysis reduced them to five independent effects. We also found multiple differences between the two age groups, with seniors responding more slowly and in a more stereotyped fashion. Multiple significant task x age interactions emerged as well, with age differences being more pronounced in E than in L. The latter finding is of practical relevance, since it suggests that age-related deficits in some real-life situations may be underestimated in laboratory research. It also is of theoretical relevance: it indicates that brain regions which are particularly vulnerable to aging may contribute to task E more than to task L.

Cost-effective policy option in launching a community-based pneumococcal vaccination program among the elderly in Japan

Shu-Ling Hoshi — 2012-07-10

In Japan, some municipalities introduced a publicly funded pneumococcal vaccination program for the elderly. The expansion of such program has become one of the current topics in the health policy arena. We aim to appraise the value for money of expanding such programs, or starting one in a municipality without a program. We conducted a cost-effectiveness analysis with Markov modelling and calculated incremental cost-effectiveness ratio value of starting such a program with 36 different design options, 3 minimum age criteria for the entitlement to the subsidy and 12 levels of co-payment. We found that the introduction of vaccination programs costs more and gains more regardless of targeting ages and co-payment levels. Estimated incremental cost-effectiveness ratios range from ¥ 8,263,340 per year-of-life-saved (targeting age 65 or over, setting co-payment level at ¥ 0) to ¥ 10,351,324 per year-of-lifesaved (targeting age 75 or over, setting co-payment level at ¥ 5000). According to cost-effectiveness acceptability curves, the probability that a vaccination program is less than ¥ 10,000,000 (US $ 1 = ¥ 100) per life-year gained ranges from 28.5% to 57.5%. By adopting the threshold of the Committee to Study Priority for Vaccine Development in the US, US $ 100,000 per quality adjusted life year gain, all the programs are almost certainly judged cost-effective as vaccination strategies.

The gender-related alterations in the telomere lenght and subtelomeric methylation in patients with Parkinson’s disease

Toyoki Maeda — 2012-07-10

The aim of this study was to determine whether Parkinson’s disease (PD) affects somatic telomeric features. Some recent reports have shown that telomere length is not changed in patients with Parkinson’s disease. In this study, we more closely evaluated possible Parkinson’s disease-associated telomeric alterations than has been done previously. We analyzed the telomere length distribution, the subtelomeric methylation status, and their gender-related differences, as well as the mean telomere length in PD patients in comparison to age-matched controls. The telomeric parameters of the peripheral leukocytes of Parkinson’s disease outpatients and normal healthy volunteers, including family members of the participating outpatients were determined by analyzing the densitometries of the Southern blot results obtained with methylation- sensitive and insensitive isoschizomers. The Parkinson’s patients had gender relateddifferences in the alterations of their telomere length and subtelomeric status. Only female patients had significant Parkinson’s diseaseassociated telomeric and subtelomeric changes. The female Parkinson’s patients bore proportionally decreased long telomeres (>9.4 Kb) and less methylation of short telomeres (<4.4 Kb) in comparison with healthy controls, both of which have been regarded to be a part of aging-associated telomeric and subtelomeric changes. These results suggested that the aging-related telomeric and subtelomeric changes are accelerated specifically in female Parkinson’s patients, and that genomic DNA is more strongly affected by Parkinson’s disease in females than in males.

The breadth of attention in old age

Stefanie Hüttermann — 2012-12-04

Older adults typically have more difficulties than younger ones in situations that require attention in the visual periphery, such as driving a car or riding a bicycle. Previous studies accordingly found that the breadth of attention decreases in old age when one attention-demanding task is presented at fixation and simultaneously another one in the visual periphery. The present work evaluates the role of eye position for the observed deficit by presenting both tasks in the visual periphery (condition peripheral-peripheral) or by leaving it up to the subjects where in the visual field the tasks appear (condition free-gaze). Our data indicate that attention breadth decreases by 27% from the age of early 20 to the age of late 60 in both conditions. This outcome generalizes previous findings about age-related attention deficits to scenarios that were not explored in previous studies, yet are relevant for everyday behavior.