Current Aging Science (v.7, #2)

A link between Alzheimer's disease (AD) and an excess presence of oxidant free radicals in the brain has frequentlybeen reported. It is generally assumed that such oxidative stress and related cellular damage is caused by inflammatorychanges in the brain and is consequent to amyloid deposition. This review makes the argument that elevated oxidativestress in AD is an early causal event in the initiation and advancement of this disease. Oxidative stress can be decreasedby enhancing antioxidant enzymes through activation of the cytoplasmic transcriptional factor (Nrf2)/ARE (antioxidantresponse element) pathway, and by dietary and endogenous antioxidant chemicals. Reduction in the binding abilityof Nrf2 to ARE lowers antioxidant enzyme levels. Decreased levels of Nrf2 and augmentation of oxidative stress inAD suggest that the ROS-dependent mechanism of activating the Nrf2/ARE pathway has become unresponsive. A combinationof agents that can either activate the Nrf2-ARE pathway by ROS-independent mechanisms, or by acting directly asantioxidant chemicals, may be necessary to reduce oxidative stress in AD. Earlier shortcomings of using individual antioxidantsmay be due to consideration of antioxidants as pharmacological agents, ignoring the fact that individual antioxidantscan be transmuted in the highly oxidant milieu that is present in AD. Interactions between various cellular compartmentsmay require simultaneous examination of more than one agent. The clinical utility of such a more integrativemethod can reveal interactive effects such as those found in nutritional research and this can compensate for any mechanisticshortcomings of simultaneous testing of more than a single agent.

Germline Genetics of the p53 Pathway Affect Longevity in a Gender Specific Manner by Sebastian Groß, Uta-Dorothee Immel, Michael Klintschar, Frank Bartel (91-100).
Aging is thought to occur through the accumulation of molecular and cellular damage. A key regulator of thecell's stress response is p53. In mice, the activity of p53 associates with lifespan. We were therefore interested whetherSNPs in members of the p53-pathway are associated with longevity in humans. We genotyped the following SNPs: p53 -rs1042522 (Arg72Pro), MDM2 - rs2279744 (SNP309), MDM4 - rs4245739 (SNP34091), rs1563828 (SNP31826),PPP2R2B (rs319217) in 155 long-lived individuals (LLIs) who died at the age of 91 and over and in 171 ethnicallymatchedcontrol subjects. Kaplan-Meier survival curves and log-Rank-test were used to determine the mean and mediansurvival times. In female LLIs, the Pro-allele of rs1042522 (Arg72Pro) and the G-allele of rs2279744 (SNP309) were significantlyassociated with an increased survival time (P =0.026, P <0.001, respectively, log-Rank-test). In contrast, therewas no difference regarding the survival time in male LLIs (rs1042522: P=0.58, rs2279744: P =0.503, log-Rank-test).There was no difference regarding the average age of death for the genotypes of the respective SNPs in the MDM4 gene(rs1563828: P =0.99; rs4245739: P =0.179, respectively). Here we show for the first time that the G-allele of rs2279744(SNP309) is associated with increased lifespan. Importantly, this effect is gender-specific. Our data support the hypothesisthat genetic variants that are associated with lower activity of p53 - and therefore increased tumor risk - are associatedwith prolonged lifespan in a gender-specific manner.

Gene-Gene and Gene-Environment Interaction on the Risk of Parkinsonµs Disease by Neeraj Kumar Singh, Basu Dev Banerjee, Kiran Bala, Mitrabasu Chhillar, Neelam Chhillar (101-109).
Background: Even with numerous studies the cause of Parkinson's disease (PD) remains elusive. It has beenhypothesized that interactions between genetic and environmental factors may play an important role in the pathogenesisof PD.;Objectives: To examine the gene-gene and gene-environment interaction on PD risk with respect to gene polymorphism ofcytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1), organochlorine pesticides (OCPs) andmetals.;Methods: This study included 70 patients of PD and 100 age-matched controls. The restriction fragment length polymorphismwas used for analysis of genetic polymorphism. OCPs and serum metal levels were estimated by using gas chromatographyand an autoanalyser respectively.;Results: The CYP2D6*4 mt and GSTP1 *B allelic variants were significantly associated with increase in PD risk. Wefound a statistically significant difference in β -hexachlorocyclohexane (β-HCH), dieldrin, 1,1-dichloro-2,2-bis(pchlorophenyl)ethylene (pp'-DDE) and copper levels between the patients and controls. We found significantly high levelsof β-HCH, dieldrin and pp'-DDE in the CYP2D6*4 mt allelic variants, β-HCH and pp'-DDE in the GSTP1*B allelic variantsand dieldrin in the GSTP1*C allelic variants when comparing CYP2D6*4 non-mt, GSTP1 non-*B and GSTP1 non-*C allelic variants in patients of PD respectively.;Conclusion: This study demonstrates that the CYP2D6*4 and GSTP1 genes may be considered as candidate genes for PDand they may also interact with β- HCH, dieldrin and pp'-DDE to influence the risk for PD.

Aging Related Changes in Mixed Basal Saliva Concentration of Sodium, Potassium and Chloride in Healthy Non Medicated Humans by Rui De Oliveira, Eunice Navas, Carolina Duran, Maria Pinto, Jose Gutierrez, Antonio Eblen-Zajjur (110-114).
It is well known that the salivary flow is reduced by aging but ionic composition changes associated to aginghave been less evaluated. To measure salivary and plasmatic [Na+], [K+] and [Cl-] and to correlate with age in healthy,non-medicated subjects of any gender, 165 healthy participating subjects (over 15 years old) were asked to give sample of5mL mix basal saliva in a plastic vial without any stimulation technique, additionally, 5mL of venous blood was collected.Samples [Na+] and [K+] were measured by flame photometry (CorningTM M-405) and [Cl-] by voltametric chlorometry(CorningTM M-920). Ionic concentrations were expressed as (X±DE; meq.L-1). All three ionic concentrations progresivelyincreased with age, with the lineal regression equation being: [Na+] mEq=17.76 + 0.26(Age); r=+0.42; F=31.5;P=0.00001; [K+] mEq=13.2+0.15(Age); r=+0.32; F=16.5; P=0.00001; [Cl-] mEq=9.05+0.18(Age); r=+0.35; F=7.8;P=0.0071. Age induced changes in salivary ionic concentrations were not associated to blood ionic changes. However, salivaand blood [Na+] and [K+] were correlated (r=+0.25; F=4.49; P=0.04 and r=+0.30; F=6.98; P=0.01, respectively). Significantassociation was found among salivary ions: [Na+] mEq=9.14+0.99[K+] (r=+0.79; F=95.2; P=0.000001); [Cl-]mEq=0.95+0.56[Na+] (r=0.79; F=106.6; P=0.000001) and [Cl-] mEq=3.45+0.69[K+] (r=0.73; F=72.5; P=0.000001).These results confirm and measure the impact of aging over the mixed and resting salivary secretion process and suggestthat local changes are not related to blood ionic composition.

Effect of Exercise on Dual-task and Balance on Elderly in Multiple Disease Conditions by Tobia Zanotto, Marco Bergamin, Fausto Roman, John C. Sieverdes, Stefano Gobbo, Marco Zaccaria, Andrea Ermolao (115-136).
Investigations on how exercise and physical activity affect dual-task (DT) performance in the elderly are growingrapidly due to the fact that DT activities are commonplace with activities of daily living. Preliminary evidence hasshown the benefit in exercise on DT balance, though it is unclear to what extent the effect exercise has on DT performancein elderly subjects with disease conditions, including subjects with a high risk of falls. Hence, the objective of thisstudy was to critically review the existing evidence of a potential relationship between exercise and improvement of static anddynamic balance during DT conditions as well as secondary outcomes in elderly subjects with different disease conditions.;A systematic search using online databases was performed to source documents. Inclusion criteria sourced articles classifiedas randomized controlled trials (RCT), controlled trials (CT) and uncontrolled trials (UT). Moreover, the studies hadto administrate an exercise or physical activity protocol in the intervention. Seventeen studies met the eligibility criteriaand were comprised of 12 RCTs, 3 CTs, and 2 UTs.;Overall, 13 studies supported exercise being effective to improve parameters of static and dynamic balance during singleor DT conditions. Despite the heterogeneity of pathologic conditions, exercise showed similar benefits to improve functionin two main areas: neurological conditions and frailty conditions. The lack of a common method to assess DT performancelimited the ability to compare different interventions directly. Future research is warranted to study the optimaldose and exercise modalities to best reduce the risk of falls in the elderly with multiple disease conditions.

Hip but Not Thigh Intramuscular Adipose Tissue is Associated with Poor Balance and Increased Temporal Gait Variability in Older Adults by Odessa Addison, Patricia Young, Mario Inacio, Woei-Nan Bair, Michelle G. Prettyman, Brock A. Beamer, Alice S. Ryan, Mark W. Rogers (137-143).
Background: Intramuscular adipose tissue (IMAT) of the lower extremity is a strong negative predictor of mobilityfunction. Variability in temporal gait factors is another important predictor of mobility function. The purpose of thisstudy was to examine the relationships between IMAT in the hip and thigh muscles, balance, and temporal gait variabilityin older adults.;Methods: Forty-eight healthy community dwelling older adults (74 +/- 1 year) underwent a CT scan to quantify IMAT inthe gluteus maximus (Gmax), gluteus medius/minimus (Gmed/min), hamstrings, vastus lateralis, and adductor muscles.Temporal Gait measures were collected on a GAITRite walkway and gait variability was determined by calculating intraindividualstandard deviations. Individuals were divided by tertiles of temporal gait variability into categories of high,medium, and low variability. Differences in the IMAT of the hip abductors were calculated for those with high and lowgait variability and partial correlations for gait variability and all muscle composition measures were determined for allvariables with normalized gait speed as a covariate.;Results: Gmed/min IMAT was greater in those with higher gait variability compared to those with lower gait variability(p<0.05). Gmed/min IMAT was related to stride width variability (r=0.30, p<0.05). Gmax IMAT was also related to timevariability of swing (r=0.42), stance (r=0.26), double limb support (r=0.43), double support loading (r=0.44), and doublesupport unloading (r=0.50) (all p<0.05).;Conclusion: Increased IMAT in the proximal hip muscles, particularly the hip abductors, was associated with increasedgait variability and poorer balance. These findings may have implications for the assessment and treatment of balance andfalls such that interventions for enhancing balance and mobility among older individuals should take into account the importanceof gluteal muscle composition.

Background: Older people are frequent users of hospital care and are at high risk of adverse outcomes such asunplanned hospital readmission after discharge. Various transitional care programmes targeting post-discharge outcomeshave been studied, utilising telephone follow-up (TFU) both as a sole intervention and as part of multi-component interventions.;Literature review findings: The effects of TFU of older people after hospital discharge as a sole intervention upon healthcareutilisation outcomes such as readmissions have not been reported to date. The individual impact of TFU in multicomponentinterventions that have reported reduced readmissions is hard to assess. There is considerable heterogeneityin terms of outcomes studied and how TFU was instituted. Outstanding questions remain about which health-care professionalshould perform TFU, when and how often it should be done after discharge, and what questions should be asked.;Conclusions: TFU of older people after hospital discharge has been reported as a feasible, low cost, minimal harm interventionwhich patients appreciate, so assessing its effectiveness in more diverse settings and randomised trials is important.