Current Aging Science (v.6, #3)

Recently the relationship between oxidative stress and aging has been brought into question. It has been suggestedthat while oxidative events may play a role in the progression of age-related pathologies, it is not relevant to agingprocesses not involving specific diseases associated with senescence. The evidence in support of this concept is largelybased on studies with the roundworm, Caenorhabditis elegans (C. elegans) that has been extensively used as a model systemto study aging. This commentary evaluates data derived from C. elegans and documents that the preponderance ofevidence from this species supports the role of pro-oxidant events as being a significant contributor to normal aging. Possiblereasons for some anomalous findings conflicting with this concept, are discussed.

Effect of Vitamin D3 on Lifespan in Caenorhabditis elegans by Jennifer A. Messing, Roschelle Heuberger, Jennifer A. Schisa (220-224).
Vitamin D is an essential micronutrient, necessary for human health. To determine if Caenorhabditis elegans(C. elegans) could function as an effective model to study the mechanisms of action of vitamin D, we asked if vitamin D3affects C. elegans lifespan. Multiple factors positively impact lifespan in this system including dietary restriction and vitaminE. In addition, the C. elegans DAF-12 nuclear hormone receptor is homologous to the vitamin D receptor in humansand is therefore a candidate for a functional vitamin D receptor. It was hypothesized that vitamin D3 supplementationwould increase the lifespan of C. elegans in a DAF-12-dependent manner. Dose-response curves were completed, and resultsindicate that exposure to 1,000 µg/ml vitamin D3 significantly increased the lifespan of wild-type worms by up to39% (p<0.001). The daf-12 mutants exposed to 1,000 µg/ml vitamin D3 lived significantly longer than daf-12 controls exposedto 0 µg/ml (p<0.001), but among worms exposed to 1,000 µg/ml vitamin D3, wild type lived significantly longerthan daf-12 (p<0.01). The data suggest that vitamin D3 can interact with multiple receptors, possibly implicating the NHRfamily of nuclear hormone receptors related to DAF-12. This research is the first to our knowledge to utilize C. elegans asa model to study the impact of vitamin D3 on longevity and supports the use of this model system to increase our understandingof vitamin D function at the cellular level, its role in cellular health, and its potential medicinal utility in humans.

Iron and Iron Chelators: A Review on Potential Effects on Skin Aging by Anne Pouillot, Ada Polla, Barbara S. Polla (225-231).
Similar to oxygen, iron is essential for aerobic life and energy production. Akin to oxygen, iron can be toxicand accelerate the aging process. Indeed, via the Fenton and Haber Weiss reactions, iron potentiates the generation ofhighly reactive oxygen free radicals such as hydroxyl radical, thus stimulating oxidative damage. The possibility thatwomen's longer life span relates to a lower iron status due to iron loss during reproductive life has been considered as avalid hypothesis, while hemochromatosis has been proposed as a model of iron overload to examine the effects of iron onthe aging process. Iron plays an aggravating role in many diseases in which iron deprivation has been shown to be beneficialincluding ischaemia-reperfusion injury, neurological disorders and muscle diseases such as Duchenne's muscular dystrophy.In the skin, excess iron combined with UV radiation exerts pro-oxidant effects while scavenging of free iron preventsor inhibits the toxic effects of UV radiation on both nude mice and human skin.;In this review, we propose that iron chelators and/or iron deprivation might play a significant role in the prevention of aging-associated diseases and conditions, in particular in the skin, and increase quality of life. Controlled iron deprivationmight be achieved by regular blood donation in which case the quality of life of both the donor and the recipient is improved.Increasing the frequency of blood donation may thus significantly contribute to both individual and social wellbeing.Furthermore, we propose the skin as an accessible model for the study of aging and the effects of iron / iron deprivationon the aging mechanisms. Finally, we suggest that the development of topical iron chelators might represent a noveland simple approach to prevent skin aging, when such prevention has proven an important factor in increasing an agingpopulations' quality of life.

Characterisation of Mitochondrial DNA Deletions by Long-PCR in Central Nervous System Regions of Young, Middle- and Old-aged Rats by Ashley Cahif, Gemma M. Parkinson, Christopher V. Dayas, Doug W. Smith (232-238).
The causes of ageing remain poorly understood, although a role for mitochondria is widely accepted. Theseunique organelles that are responsible for a cell's energy, rely on their own small genome and translational machinery toproduce proteins that, together with nuclear genome encoded proteins, form the electron transport chain complexes necessaryfor ATP production. Various forms of mitochondrial genome mutation and rearrangements are thought to be involvedin the ageing process, particularly in post-mitotic cells, such as those of the nervous system. In the present study, we havecharacterised mitochondrial DNA (mtDNA) deletion mutations in five central nervous system (CNS) regions of theyoung, middle-aged, and old Fischer 344 (F344) rats. DNA was extracted from the cerebral cortex, striatum, midbrain,cerebellum and spinal cord, and long-PCR was used to detect mtDNA with deletions in the minor and major arcs. Thisapproach has the advantage that all deletions can be detected without a priori knowledge of breakpoints. In the minor arc,we found evidence for deletions in the striatum of five out of six old animals and in the spinal cords from two of six oldanimals. In contrast, mtDNA deletions in the major arc appeared markedly more abundant, both in terms of affected CNSregions and number of deleted mtDNA molecules. Furthermore, major arc deletions were apparent earlier with a numberof CNS regions showing deletions in the middle-aged group. The cerebral cortex, striatum and spinal cord were the mostaffected regions, while the midbrain and cerebellum were relatively spared. These findings are remarkably consistent withprevious human brain data and further underscore the value of the rat model for investigation of ageing-related changes inthe mitochondrial genome.

The effects of ethanolic extracts of whole plants of Bacopa monnieri (BME), Evolvulus alsinoides (EAE), Tinosporacordifolia (TCE) and their combinations in equal proportion [CEP-1 (BME+EAE), CEP-2 (BME+TCE), CEP-3(EAE+TCE) and CEP-4 (BME+EAE+TCE)] were tested in amnesic rats using Radial arm maze task performance (RAM)and Barnes maze test at 200 mg/kg p.o. The latency to find food and target hole was observed in RAM and Barnes mazerespectively. Cognitive dysfunction was induced by scopolamine (0.3 mg/kg i.p.) treatment. BME, EAE, TCE and theircombinations of equal proportion (CEPs) showed significant decrease in latency to find food and target hole in RAM andBarnes maze respectively. Inter comparison among single extract alone treated groups revealed that BME treated animalsshowed significant difference as compared to EAE and TCE treated animals. All combinations of equal proportion (CEPs)of these extracts showed significant difference in latency to find food and target hole as compared to single extractstreated animals. CEP-1 showed significantly better effect as compared to CEP-2 and CEP-3. Significant difference in latencyto find food and target hole was also present between CEP-2 and CEP-3. Effect of CEP-4 was found to be significantlybetter than CEP-1, CEP-2 and CEP-3 treated rats in both models. From present investigation, it was concluded thatethanolic extract of Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia provided better nootropic effectwhen used in combination.

Dynamics of Telomere Length in Different Age Groups in a Latvian Population by Egija Zole, Liana Pliss, Renate Ranka, Astrida Krumina, Viesturs Baumanis (244-250).
The shortening of telomeres with ageing is a well-documented observation; however, the reported number ofnucleotides in telomeres varies between different laboratories and studies. Such variability is likely caused by ethnic differencesbetween the populations studied. Until now, there were no studies that investigated the variability of telomerelength in a senescent Latvian population of the most common mitochondrial haplogroups, defined as H (45%), U (25%),Y chromosomal N1c (40%) and R1a1 (40%). Telomere length was determined in 121 individuals in different age groups,including a control group containing individuals of 20-40 years old and groups of individuals between 60-70 years old,71-80 years old, 81-90 years old, and above 90 years old. Telomere length was determined using the Southern blot telomericrestriction fragment assay (TRF). Decreased telomere length with ageing was confirmed, but a comparison of centenariansand individuals between 60-90 years of age did not demonstrate a significant difference in telomere length.However, significant variability in telomere length was observed in the control group, indicating probable rapid telomereshortening in some individuals that could lead up to development of health status decline appearing with ageing. Telomerelength measured in mononuclear blood cells (MNC) was compared with the telomere length measured in whole peripheralwhite blood cells (WBC) using TRF. Telomere length in MNC was longer than in WBC for the control group with individuals20 to 40 years old; in contrast, for the group of individuals aged 65 to 85 years old, measured telomere length wasshorter in MNC when compared to WBC.

Creatine Supplementation: Can it Improve Quality of Life in the Elderly without Associated Resistance Training? by Anna Moon, Lara Heywood, Stephen Rutherford, Christian Cobbold (251-257).
Introduction: Ageing is associated with decreased muscle mass, strength, power and function, and reduction inbone density and mineral content, leading to reduced independence and increased risk of falls. Creatine supplementation isreported to improve muscular strength and performance with training in younger athletes, and therefore could benefitolder individuals.;Aims: This review critically appraises the current literature on whether creatine supplementation enhances muscular performanceand function, body composition, bone mineral density and content in older adults without the addition of resistancetraining, and thus determines whether creatine supplementation can lead to an improved lifestyle for the sedentaryelderly population.;Results: There is conflicting evidence regarding the usefulness of creatine supplementation in older subjects. Generally,however, creatine supplementation, without associated resistance training, seems to enhance muscular strength, power andendurance, increase lean body mass (LBM) and improve the functional capacity of the elderly. Furthermore, it has beendemonstrated that increased muscle mass due to creatine supplementation can result in increased local bone density. It appearsthat the effect of creatine supplementation is more beneficial in larger muscles and less effective in smaller muscles,however there are exceptions. The mechanism by which creatine supplementation works requires further research, howeverit is likely that the effects of creatine are related to creatine kinase activity, providing enhanced energy production forgreater muscular contraction.;Conclusions: These data indicate that creatine supplementation without associated training in the elderly could potentiallydelay atrophy of muscle mass, improve endurance and strength, and increase bone strength, and thus may be a safe therapeuticstrategy to help decrease loss in functional performance of everyday tasks.

Analyses of Associations Between Reactive Oxygen Metabolites and Antioxidant Capacity and Related Factors Among Healthy Adolescents by Kazuyoshi Tamae, Toshiharu Eto, Kazuhiro Aoki, Shingo Nakamaru, Kazunori Koshikawa, Kazuhiko Sakuma, Takeshi Hirano (258-265).
Evidence based on epidemiologic investigations using biochemical parameter is meaningful for health promotionand administration among adolescents. We conducted Reactive Oxygen Metabolites (ROM) and Biological AntioxidantPotentials (BAP) tests, along with a questionnaire survey, for a sample of 74 high school students (16.51±0.11 yearsof aged mean±SE), to investigate the associations between ROM, BAP, and related factors, including BMI and blood biochemicaldata. Venous blood samples (approximately 7cc) were collected. At the same time, each individual's informationwas obtained from the questionnaire. The mental health status was investigated using the Center for Epidemiologic StudyDepression scale (CES-D) included in the same questionnaire. The mean values and standard errors of all variables werecalculated. In addition, the relationships between ROM and BAP with these factors were analyzed. The results revealedthe preferred levels of ROM (261.95 ± 9.52 U.CARR) and, BAP (2429.89±53.39 µmol / L) and blood biochemical data.Few significant relationships between two markers and related factors were found. So, we detected a cluster with an imbalancebetween ROM and BAP, which means low antioxidant ability, whereas the other clusters had conditions withmoderate balance or good balance between them. Moreover, we determined the Oxidative stress-Antioxidant capacity ratio(OAR), using the ROM and BAP values, in order to clarify the characteristic of the detected clusters.However, comparativeanalyses across the three clusters did not yield significant differences in all related factors. No correlations betweenROM, BAP and related factors were indicated, although significant association between ROM and BAP was observed(R2=0.1156, R=0.340, P=0.013). The reason for these results can be explained by the influences of good health andyoung age. On the other hand, present study suggests that some latent problems among adolescents may be related to unhealthyconditions in the future. Also, this study indicated that ROM and BAP may be useful as markers of the oxidativestress status. After this, further investigations using biomarkers based on epidemiologic design should be conducted, toreveal the reliability of the present results.

The Effects of Sarcopenia on Muscles with Different Recruitment Patterns and Myofiber Profiles by Michael R. Deschenes, Jennifer R. Gaertner, Shaelyn O'Reilly (266-272).
Sarcopenia, or the age-related loss of muscle size/mass, is a major health concern in western societies whereaging is prevalent. Currently, more is known about sarcopenia's impact on health and quality of life, than its physiologicaletiology. It remains to be clearly determined whether the onset and progression of sarcopenia is similar throughout thebody (systemic), or is more localized to certain muscles and myofiber types comprising those muscles (local). The objectiveof this project was to quantify the systemic vs. local nature of sarcopenia. Three muscles of different myofiber typecomposition and/or function (Soleus, Plantaris, EDL) were collected from 10 young adult rats, and 10 aged rats. Immunohistochemicalprocedures were then performed on frozen muscle sections to determine average myofiber size, fiber typecomposition, and relative areas of muscles occupied by each myofiber type. Significant (P ≤ 0.05) overall age-relatedmyofiber atrophy occurred in the predominantly fast-twitch, non-postural Plantaris and EDL muscles, but not in the primarilyslow-twitch, postural Soleus. Moreover, age-related atrophy was significantly (~100%) greater in the EDL than thePlantaris. Age-related myofiber type conversion also demonstrated muscle specificity in that all fiber types were affectedin the Soleus, compared to three of the four myofiber types of the Plantaris, and only one of the four myofiber types identifiedin the EDL. In sum, these data suggest that although sarcopenia may be ubiquitous among skeletal muscles, the degreeof its impact displays specificity based not only on myofiber type composition, but also on muscle function.

The Mini-Mental Parkinsonµs (MMP) as a Cognitive Screening Tool in People with Parkinsonµs Disease by Robert Caslake, Fiona Summers, Douglas McConachie, Catriona Ferris, Joanna Gordon, Clare Harris, Linda Caie, Carl Counsell (273-279).
Background: Cognitive decline is common in Parkinson's disease (PD) but may not be adequately identified bythe mini-mental state examination (MMSE), which is better suited to Alzheimer's disease. The mini-mental Parkinson(MMP) examination is a cognitive screening tool designed in French specifically for PD. We aimed to establish the validityand reliability of the English language version of the MMP compared with the MMSE.;Methods: People with various stages of PD underwent testing with the MMP and MMSE, which was then compared witha reference standard battery of neuropsychological tests to identify those with significant cognitive impairment.;Results: Forty-nine patients were recruited. Both the MMP and MMSE were significantly correlated with scores on all theneuropsychological tests in the validation battery. The median MMP score was proportionally lower (80% of maximum)than the MMSE (90% of maximum) in PD patients with cognitive impairment and those with prior neuropsychiatric complicationsbut there was no difference between the MMP and MMSE in areas under the curves (0.84) for detecting cognitiveimpairment. Test-retest reliability of the MMP was good (intra-class correlation coefficient 0.793). An MMP of 28 orlower out of 32 detected cognitive impairment with 87% sensitivity and 76% specificity.;Discussion: The English language version of the MMP has now been validated. It detects more cognitive deficits in PDpatients than the MMSE and identifies significant cognitive impairment in those with PD at least as well as the MMSE.

Age-related disturbances of the sleep-wake cycle can reflect ontogenetic changes in regulatory mechanisms underlyingnormal and pathological aging, but the exact nature of these changes remains unclear. The present report is thefirst attempt to apply principal component analysis to the electroencephalographic (EEG) spectrum to examine of whetherthe observed age-related changes in the objective sleep measures can be linked to the opponent sleep-promoting andwake-promoting processes. The EEG indicators of these processes - scores on the 1st and 2nd principal components of theEEG spectrum, respectively - were compared in 15 older (57-74 years) and 16 younger (20-31 years) healthy volunteers.The scores were calculated for non-REM sleep episodes which occurred during ten 75-min naps scheduled every 150 minthroughout a 40-h constant routine protocol. Both, a decrease of the 1st principal component score and an increase of the2nd principal component score were found to contribute to such most obvious age-related modification of the sleep EEGspectrum as attenuation of EEG slow-wave activity in older people. Therefore, we concluded that the normal aging processcan reflect both a weakening of the sleep-promoting process and a strengthening of the wake-promoting process, respectively.Such bidirectional changes in chronoregulatory processes may explain why sleep of older people is characterizedby the few profitable and a number of detrimental features (i.e., a better ability to cope with daytime sleepiness andsleep loss vs. difficulty of falling asleep, decreased total nighttime sleep, “lightened” and fragmentized sleep, unwantedearly morning awakenings, etc.).