Current Aging Science - Volume 6, Issue 3, 2013

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

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 D3 affects C. elegans lifespan. Multiple factors positively impact lifespan in this system including dietary restriction and vitamin E. In addition, the C. elegans DAF-12 nuclear hormone receptor is homologous to the vitamin D receptor in humans and is therefore a candidate for a functional vitamin D receptor. It was hypothesized that vitamin D3 supplementation would increase the lifespan of C. elegans in a DAF-12-dependent manner. Dose-response curves were completed, and results indicate that exposure to 1,000 µg/ml vitamin D3 significantly increased the lifespan of wild-type worms by up to 39% (p<0.001). The daf-12 mutants exposed to 1,000 µg/ml vitamin D3 lived significantly longer than daf-12 controls exposed to 0 µg/ml (p<0.001), but among worms exposed to 1,000 µg/ml vitamin D3, wild type lived significantly longer than daf-12 (p<0.01). The data suggest that vitamin D3 can interact with multiple receptors, possibly implicating the NHR family of nuclear hormone receptors related to DAF-12. This research is the first to our knowledge to utilize C. elegans as a model to study the impact of vitamin D3 on longevity and supports the use of this model system to increase our understanding of vitamin D function at the cellular level, its role in cellular health, and its potential medicinal utility in humans.

Similar to oxygen, iron is essential for aerobic life and energy production. Akin to oxygen, iron can be toxic and accelerate the aging process. Indeed, via the Fenton and Haber Weiss reactions, iron potentiates the generation of highly reactive oxygen free radicals such as hydroxyl radical, thus stimulating oxidative damage. The possibility that women’s longer life span relates to a lower iron status due to iron loss during reproductive life has been considered as a valid hypothesis, while hemochromatosis has been proposed as a model of iron overload to examine the effects of iron on the aging process. Iron plays an aggravating role in many diseases in which iron deprivation has been shown to be beneficial including 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 prevents or 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 deprivation might 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 deprivation on the aging mechanisms. Finally, we suggest that the development of topical iron chelators might represent a novel and simple approach to prevent skin aging, when such prevention has proven an important factor in increasing an aging populations’ quality of life.

The causes of ageing remain poorly understood, although a role for mitochondria is widely accepted. These unique organelles that are responsible for a cell’s energy, rely on their own small genome and translational machinery to produce proteins that, together with nuclear genome encoded proteins, form the electron transport chain complexes necessary for ATP production. Various forms of mitochondrial genome mutation and rearrangements are thought to be involved in the ageing process, particularly in post-mitotic cells, such as those of the nervous system. In the present study, we have characterised mitochondrial DNA (mtDNA) deletion mutations in five central nervous system (CNS) regions of the young, 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. This approach 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 old animals. In contrast, mtDNA deletions in the major arc appeared markedly more abundant, both in terms of affected CNS regions and number of deleted mtDNA molecules. Furthermore, major arc deletions were apparent earlier with a number of CNS regions showing deletions in the middle-aged group. The cerebral cortex, striatum and spinal cord were the most affected regions, while the midbrain and cerebellum were relatively spared. These findings are remarkably consistent with previous human brain data and further underscore the value of the rat model for investigation of ageing-related changes in the mitochondrial genome.

The effects of ethanolic extracts of whole plants of Bacopa monnieri (BME), Evolvulus alsinoides (EAE), Tinospora cordifolia (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 maze respectively. Cognitive dysfunction was induced by scopolamine (0.3 mg/kg i.p.) treatment. BME, EAE, TCE and their combinations of equal proportion (CEPs) showed significant decrease in latency to find food and target hole in RAM and Barnes maze respectively. Inter comparison among single extract alone treated groups revealed that BME treated animals showed 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 extracts treated animals. CEP-1 showed significantly better effect as compared to CEP-2 and CEP-3. Significant difference in latency to find food and target hole was also present between CEP-2 and CEP-3. Effect of CEP-4 was found to be significantly better than CEP-1, CEP-2 and CEP-3 treated rats in both models. From present investigation, it was concluded that ethanolic extract of Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia provided better nootropic effect when used in combination.

The shortening of telomeres with ageing is a well-documented observation; however, the reported number of nucleotides in telomeres varies between different laboratories and studies. Such variability is likely caused by ethnic differences between the populations studied. Until now, there were no studies that investigated the variability of telomere length 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 telomeric restriction fragment assay (TRF). Decreased telomere length with ageing was confirmed, but a comparison of centenarians and 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 telomere shortening in some individuals that could lead up to development of health status decline appearing with ageing. Telomere length measured in mononuclear blood cells (MNC) was compared with the telomere length measured in whole peripheral white blood cells (WBC) using TRF. Telomere length in MNC was longer than in WBC for the control group with individuals 20 to 40 years old; in contrast, for the group of individuals aged 65 to 85 years old, measured telomere length was shorter in MNC when compared to WBC.

Introduction: Ageing is associated with decreased muscle mass, strength, power and function, and reduction in bone density and mineral content, leading to reduced independence and increased risk of falls. Creatine supplementation is reported to improve muscular strength and performance with training in younger athletes, and therefore could benefit older individuals. Aims: This review critically appraises the current literature on whether creatine supplementation enhances muscular performance and function, body composition, bone mineral density and content in older adults without the addition of resistance training, and thus determines whether creatine supplementation can lead to an improved lifestyle for the sedentary elderly 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 and endurance, increase lean body mass (LBM) and improve the functional capacity of the elderly. Furthermore, it has been demonstrated that increased muscle mass due to creatine supplementation can result in increased local bone density. It appears that 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, however it is likely that the effects of creatine are related to creatine kinase activity, providing enhanced energy production for greater muscular contraction. Conclusions: These data indicate that creatine supplementation without associated training in the elderly could potentially delay atrophy of muscle mass, improve endurance and strength, and increase bone strength, and thus may be a safe therapeutic strategy to help decrease loss in functional performance of everyday tasks.

Evidence based on epidemiologic investigations using biochemical parameter is meaningful for health promotion and administration among adolescents. We conducted Reactive Oxygen Metabolites (ROM) and Biological Antioxidant Potentials (BAP) tests, along with a questionnaire survey, for a sample of 74 high school students (16.51±0.11 years of aged mean±SE), to investigate the associations between ROM, BAP, and related factors, including BMI and blood biochemical data. Venous blood samples (approximately 7cc) were collected. At the same time, each individual’s information was obtained from the questionnaire. The mental health status was investigated using the Center for Epidemiologic Study Depression scale (CES-D) included in the same questionnaire. The mean values and standard errors of all variables were calculated. In addition, the relationships between ROM and BAP with these factors were analyzed. The results revealed the 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 imbalance between ROM and BAP, which means low antioxidant ability, whereas the other clusters had conditions with moderate 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, comparative analyses across the three clusters did not yield significant differences in all related factors. No correlations between ROM, 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 and young age. On the other hand, present study suggests that some latent problems among adolescents may be related to unhealthy conditions in the future. Also, this study indicated that ROM and BAP may be useful as markers of the oxidative stress status. After this, further investigations using biomarkers based on epidemiologic design should be conducted, to reveal the reliability of the present results.

Sarcopenia, or the age-related loss of muscle size/mass, is a major health concern in western societies where aging is prevalent. Currently, more is known about sarcopenia’s impact on health and quality of life, than its physiological etiology. It remains to be clearly determined whether the onset and progression of sarcopenia is similar throughout the body (systemic), or is more localized to certain muscles and myofiber types comprising those muscles (local). The objective of this project was to quantify the systemic vs. local nature of sarcopenia. Three muscles of different myofiber type composition and/or function (Soleus, Plantaris, EDL) were collected from 10 young adult rats, and 10 aged rats. Immunohistochemical procedures were then performed on frozen muscle sections to determine average myofiber size, fiber type composition, and relative areas of muscles occupied by each myofiber type. Significant (P ≤ 0.05) overall age-related myofiber atrophy occurred in the predominantly fast-twitch, non-postural Plantaris and EDL muscles, but not in the primarily slow-twitch, postural Soleus. Moreover, age-related atrophy was significantly (~100%) greater in the EDL than the Plantaris. Age-related myofiber type conversion also demonstrated muscle specificity in that all fiber types were affected in the Soleus, compared to three of the four myofiber types of the Plantaris, and only one of the four myofiber types identified in the EDL. In sum, these data suggest that although sarcopenia may be ubiquitous among skeletal muscles, the degree of its impact displays specificity based not only on myofiber type composition, but also on muscle function.

Background: Cognitive decline is common in Parkinson’s disease (PD) but may not be adequately identified by the 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 validity and 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 with a 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 the neuropsychological 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 complications but there was no difference between the MMP and MMSE in areas under the curves (0.84) for detecting cognitive impairment. Test-retest reliability of the MMP was good (intra-class correlation coefficient 0.793). An MMP of 28 or lower 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 PD patients 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 underlying normal and pathological aging, but the exact nature of these changes remains unclear. The present report is the first attempt to apply principal component analysis to the electroencephalographic (EEG) spectrum to examine of whether the observed age-related changes in the objective sleep measures can be linked to the opponent sleep-promoting and wake-promoting processes. The EEG indicators of these processes - scores on the 1st and 2nd principal components of the EEG 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 min throughout a 40-h constant routine protocol. Both, a decrease of the 1st principal component score and an increase of the 2nd principal component score were found to contribute to such most obvious age-related modification of the sleep EEG spectrum as attenuation of EEG slow-wave activity in older people. Therefore, we concluded that the normal aging process can 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 characterized by the few profitable and a number of detrimental features (i.e., a better ability to cope with daytime sleepiness and sleep loss vs. difficulty of falling asleep, decreased total nighttime sleep, “lightened” and fragmentized sleep, unwanted early morning awakenings, etc.).