Current Aging Science - Volume 11, Issue 1, 2018

Background: Physical activity is known for its many health benefits; among them being the positive effect on bone health during the life cycle. During childhood, physical stress stimulates bone remodeling and increases density. However, due to hormonal changes during adulthood, and mainly during postmenopause the rate of bone remodeling is slowed down and is less efficient. As a result, argument has arisen in the literature regarding the benefit or harm of physical activity on bone health among postmenopausal women. Objective: The study aims to examine the efficacy of physical activity for improving Bone Mineral Density (BMD) in postmenopausal women based on a review of the literature. Methods: The articles included in the review were chosen from three databases (PubMed, SPORT Discus with full text and Science Direct). Only publications with intervention studies which provided BMD measures clearly affected by physical activity in postmenopausal women were included. Twelve articles met the criteria for inclusion. Results: In general, physical activity had a positive effect on BMD. Exercise prevented bone loss and in some cases, it contributed to the increase in BMD. Conclusion: Physical activity may improve BMD in postmenopausal women. However, the exact type of activity, its intensity, its duration and its frequency, are still unclear. Further studies are needed to determine the precise training protocol for postmenopausal women.

Background: Chronic administration of D-galactose (GAL) induces changes that resemble natural aging in rodents. Oxidative stress and Advanced Glycation End products (AGE) formation play a role in GAL-induced aging. Carnosine (CAR; β-alanyl-L-histidine) has antioxidant and anti-glycating actions and may be a potential therapeutic agent in aging due to these properties. The effect of CAR supplementation on AGE levels and oxidative stress parameters was investigated in serum, liver and brain tissues in GAL-treated rats. Methods: GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) was applied to male rats for two months. AGE, Advanced Oxidized Protein Products (AOPP), Protein Carbonyl (PC) and Malondialdehyde (MDA) levels together with Reactive Oxygen Species (ROS) formation and Ferric Reducing Antioxidant Power (FRAP) values were determined. Results: GAL treatment elevated AGE levels, ROS formation and protein and lipid oxidation products in serum and examined tissues. CAR treatment was observed to decrease significantly glycooxidative stress in serum, liver and brain tissues of GAL-treated rats. Conclusion: Our results indicate that CAR may be useful for decreasing oxidative stress and glycation products in GAL-induced aging model in rats.

Background: Age-associated loss of liver function has been recognized for decades. But, the mechanism driving liver regeneration and its decline with age remains elusive. Objective: Hence, to support of our previous studies about anti-aging effects of Ursolic Acid (UA), a compound which is extensively present in apple peels. The aim of this study is to address whether UA might alter sensors of the cell metabolic state such as SIRT1, SIRT6, PGC-1β and Klotho proteins. Methods: To evaluate the effect of UA on hepatic indicated proteins, mice were administrated with UA twice daily for 7 days. The involvements of these proteins in the UA-mediated effect harmony hepatic protection were investigated by immunofluorescence microscopy technique. Results: Our findings clearly illustrated that UA enhanced SIRT1 (~ 5 ± 0.2 folds) and SIRT6 (~ 8 ± 0.5 folds) proteins levels in hepatic, p<0.001. In addition, the data showed that UA increased PGC-1β (~ 7 ± 0.4 folds) protein overexpression, p<0.001. Moreover, we showed that UA upregulated Klotho (~ 3.5 ± 0.2 folds) protein in order to improve hepatic performance, p<0.01. Conclusion: Our results suggest that UA through increasing of SIRT1 up-regulation ameliorate reverse cholesterol transport, fatty acid use and oxidative stress defense. In addition, it seems that UA by enhancing of SIRT6 expression promotes cholesterol homeostasis through repressing SREBP1 and SREBP2. Reciprocally, UA might be involved in VLDL synthesis and exportation through PGC-1β up-regulation. Finally, UA might be as key regulators of mineral homeostasis and bile acid/cholesterol metabolism, by inducing Klotho overexpression.

Background: Although genetic variations are heritable, some quantitative traits like longevity may have non-genomic influence on heritability. Laboratory-selected inbred strains of extended longevity phenotype of Drosophila offer an opportunity to study the inheritance of longevity. Objective: The aim of the study was to examine the heritability of longevity in an extended longevity phenotype of Drosophila melanogaster using reciprocal cross effects in F1 and F2 generations. Methods: Lifespan variations of virgin and mated flies in parent, F1 and F2 generations were investigated using reciprocal crosses between normal and long lifespan lines of inbred population of D. melanogaster. Heterosis, narrow-sense heritability, recombination loss, maternal effect and overdominance with respect to survivorship in virgin and mated flies were analyzed. Results: Virgin flies lived longer than mated flies. There was no significant effect of mid-parent heterosis, recombination loss and overdominance on variations in longevity, whereas, significant maternal effect and narrow-sense heritability were observed in mated and virgin flies, respectively. Conclusion: Absence of heterosis in our study population of Drosophila phenotypes could be due to the lack of genetic heterogeneity. The heritability of the longevity trait in an inbred extended longevity phenotype depends on the variations in genetic and environmental factors.

Background: Advances in big data analytics can enable more effective and efficient research processes, with important implications for aging research. Translating these new potentialities to research outcomes, however, remains a challenge, as exponentially increasing big data availability is yet to translate into a commensurate era of ‘big knowledge,’ or exponential increases in biomedical breakthroughs. Some argue that big data analytics heralds a new era associated with the ‘end of theory.’ According to this perspective, correlation supersedes causation, and science will ultimately advance without theory and hypotheses testing. On the other hand, others argue that theory cannot be subordinate to data, no matter how comprehensive data coverage may ultimately become. Objective: Given these two tensions, namely (i) between exponential increases in data that have not translated into exponential increases in biomedical research outputs; and (ii) between the promise of comprehensive data coverage and inductive data-driven modes of enquiry versus theory-driven deductive modes, this critical review seeks to offer useful perspectives of big data analytics and to derive certain theoretical implications for aging research. Method: This work offers a critical review of theory and literature relating big data to aging research. Result: The rise of big data provides important insights into the theory development process itself, highlighting potential for holistic theoretical assemblage to ultimately enable near real time research capability. Conclusion: Big data may represent a new paradigm of aging research that can dramatically increase the rate of scientific breakthroughs, but innovative theory development remains key to this potential.

Background: DNA helicases maintain genome stability, and their deficiency is associated with disorders resembling premature aging as well as contributes to carcinogenesis. Their functions are determined by the respective genes encoding nucleotide excision repair initiating proteins, e.g. XPD and CSB. Objective: The present study aimed to investigate the influence of genetic variations in ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on lifespan and developing age-related bladder cancer focusing on homozygous wild type alleles. Method: The allelic variants were identified in 354 clinically healthy controls and 418 bladder cancer patients using the PCR-RFLP method. Results: The age-depended increase in frequencies of homozygous carriers of wild-type XPD 312Asp and XPD 751Lys alleles was observed among controls, especially among subjects over 80 years (r = 0.67, p = 0.012). The statistically significant correlation was also found between the frequency of homozygous wild type alleles at all tested loci and age in healthy population over 60 years (r = 0.35, p = 0.046) suggesting the relationship between lifespan and longevity, on one hand, and normal functioning of these genes and their products, on the other hand. Homozygous carriers of wild type alleles were less susceptible to bladder cancer, tumor invasion, increase in grade of malignancy and recurrence, but their effects were specific with respect to clinicopathological and lifestyle characteristics. Conclusion: Homozygous wild type alleles encoding XPD and CSB proteins with optimal properties were shown to affect human lifespan, risk of developing bladder cancer, its progression and recurrence under certain conditions.

Background: Most syndromes of accelerated aging are caused by mutations affecting the integrity of the genetic material. Among them, the most studied is Werner's syndrome, “adult progeria”, caused by a recessive autosomal mutation with a frequency of 1 in 10 million, which affects a helicase involved in DNA repair. In Werner syndrome, there is a loss of heterochromatin, though the stability of heterochromatin is also affected in "normal" aging. The Hutchinson-Gilford Progeria Syndrome (HGPS), "child progeria", has an even lower frequency. In most cases, it is caused by a point mutation of a gene coding a protein in the nuclear envelope, lamin A. Objectives: HGPS may provide valuable insights into the aging process. The symptoms of this condition do not entirely overlap with those of “normal” aging. Method: A critical analysis of the accelerated aging syndromes may explain what aging is, and also why some tissues and organs age at accelerated rates as compared to other tissues. Results: In this article, we will discuss the implications of HGPS and other accelerated aging syndromes in the light of the biochemical hypothesis of aging we advanced. According to this hypothesis, some reactions are less stimulated and diminish in time, affecting not only specific biochemical functions, but cellular energy, and therefore its capacity for synthesis. Conclusion: Besides, a new vision on aging, possible therapeutic strategies for these conditions and others, with similar mechanisms, are also presented.

Background: Muscle strength is a sensitive indicator of morbidity and mortality in older adults. Loss of muscle strength contributes to a decline in physical functioning. Hand grip strength is a simple measurement but correlated with total body muscle strength. This study evaluated the patterns and correlates of grip strength among older adults in the United States. Method: The grip strength data were analyzed from the National Health and Nutrition Examination Survey. Result: Individuals (n=1009) aged ≥65 years old who had a grip strength measure were included in this analysis. Age distribution was 31.5%, 27.2%, 16.2%, and 25.0% for 65-69, 70-74, 75-79, and 80+ respectively. Race distribution was 81.1%, 8.3%, 7.1%, and 3.5% for Whites, Blacks, Hispanics, and Asians respectively. The mean grip strength was 71.7kg in males and 44.6kg in females, and declined as age increased (p<.0001). Blacks had the highest grip strength, followed by Whites and Hispanics, and Asians had the lowest measure (p<.0001). Although several variables were found to be correlated with grip strength univariately, after adjusting for gender, age, and race, the factors that remained significantly and independently associated with weak grip strength were lower body weight, not being in good health status, and physical limitations. Conclusion: Grip strength reduced as age increased. Blacks and Whites displayed higher grip strength than Asians and Hispanics. General health status, weight status and physical functioning were independently associated with grip strength. These findings suggest that grip strength could be a useful indicator for overall health assessment in older adults.