Current Aging Science (v.6, #2)

Increased Protein Oxidation and Loss of Protein-Bound Sialic Acid in Hepatic Tissues of D-galactose Induced Aged Rats by Ufuk Cakatay, Seval Ayd|n, P|nar Atukeren, Karolin Yanar, Mustafa E. Sitar, Enis Dalo, Ezel Uslu (135-141).
A redox basis of the increased oxidative protein damage and free radical-mediated desialylation have not beenfully elucidated in aging. It is well known that the incidence of several liver diseases increase with age. This original researchfocuses on protein oxidation mechanisms and protein-bound sialic acid levels in liver tissue of the mimetic agingrats. Injection of D-galactose (60 mg/kg/day) for six weeks to male Sprague-Dawley rats (20-week-old) used to establishmimetic aging model. We investigated the tissue levels of various protein oxidation markers such as protein carbonylgroups, suitable advanced oxidation protein products and protein thiol groups. Our study also covered protein-bound sialicacid in liver tissue of D-galactose-induced aging rats. PCO (Protein Carbonyl Groups), P-OOH (Protein Hydroperoxides)and AOPP (Advanced Oxidation Protein Products) levels in aging rats were significantly higher compared to young controlgroups. On the other hand, P-SH (Protein Thiol Groups) levels were not found to be different between two groups. SA(Sialic Acid) levels in D-galactose-induced aging rats were significantly lower compared to control groups. Our resultsdemonstrated greater susceptibility to hepatic oxidative protein damage and desialylation of hepatocellular proteins in Dgalactose-induced aging rats. These molecular mechanisms may be operative in the many age-related liver diseases, whichare pertinent to increased oxidative stress and altered redox homeostasis.

Melatonin Decreases Levels of S100β and NFΚB, Increases Levels of Synaptophysinina Rat Model of Alzheimer’s Disease by Zhou Jun, Zhou Li, Wang Fang, Yang Fengzhen, Wen Puyuan, Li Wenwen, Song Zhi, Stephen C. Bondy (142-149).
The effect of treatment with melatonin was investigated in a rat model of Alzheimer’s disease (AD) involving asingle intra-hippocampal injection of amyloid peptide A β1-42. Thirty days after this injection immunohistochemical analysisrevealed significant increases of both S-100β and NFΚB in cortex and hippocampus of treated animals. Levels of synaptophysinwere depressed following treatment and this was confirmed by Western blotting. Histopathological studies revealeda diminution of neuronal cell number in the CA3 area of the hippocampus. Behaviorally, the rate of learning escapefrom electroshock using a maze box was diminished in Aβ-treated mice. Another group of A treated also receivedan oral gavage of 0.5 mg/kg melatonin on each of the 30 days between Aβ treatment and sacrifice. The effect of this repeatedmelatonin exposure was to reverse Aβ-induced changes in CA3 cell number and S-100 levels. The increased cerebralcontent of NF-Κ B and the behavioral changes caused by A treatment were partially reversed by melatonin. However,melatonin administration had no effect on the reduced level of synaptophysin in Aβ-treated mice. Overall, thesefindings suggest that melatonin may exert a potentially beneficial effect upon the progression of AD.

Mediterranean Diet and Dementia of the Alzheimer Type by Neville Vassallo, Charles Scerri (150-162).
Dementia of the Alzheimer type is the most common form of dementia affecting mostly the elderly population.It is a progressive and fatal neurodegenerative disorder with characteristic neuropathology and clinical symptomology. Inthe coming years, the number of individuals with Alzheimer’s disease (AD) will increase as the elderly populationworldwide is expected to grow significantly thus putting an added strain on national health care systems as well ascaregivers who will inevitably carry most of the care burden. Thus it has been suggested that early intervention strategieswhich delay or halt the disease progression will have a strong impact on clinical outcomes. Changes in lifestyle habitssuch as diet modification or supplementation have been indicated as probable protective factors for a number of chronicconditions including AD. Particular attention has recently been devoted to the Mediterranean diet which is rich in theantioxidants Vitamins C and E, polyunsaturated fatty acids and polyphenolic compounds. Several in vitro, animal andpopulation-based studies reported a positive effect between adherence to a Mediterranean diet and AD prevention,although contrasting views remain. This review will focus on the latest developments and findings in the ongoing researchinvestigating the relationship between Mediterranean diet and its major constituents in AD onset and progression.

We have investigated age-related changes in the reliability of glutathione-related antioxidant enzyme defense inmonkeys that differ in adaptive behavior. Activities of gluthatione reductase (GR), glutathione peroxidase (GSH-Px), andgluthatione-S-transferase (GST) and also lipid peroxidation products (TBARS) under basal conditions and under acutepsycho-emotional stress were evaluated in erythrocytes of young (6-8 years) and old (20-27 years) female rhesus monkeyswith depression-like and standard (control) behavior. We have found that young animals with depression-like behavior, incomparison with young monkeys of standard behavior, demonstrated higher activity of GR in basal conditions and no significantchanges in response to acute immobilization stress. With aging the activity of GR increased in monkeys withstandard behavior in basal conditions but retained the ability to increase under acute stress. At the same time during agingin monkeys with depression-like behavior GR activity did not undergo significant changes in basal conditions and did notchange in response to acute stress. Moreover, old animals with depression-like behavior demonstrated reduced activity ofGSH-Px. More pronounced disturbances in GR and GSH-Px activities in animals with depression-like behavior evidencea more marked decrease in the reliability of antioxidant enzyme defense of cells and lead to activation of lipid peroxidationthat may be considered as an important factor of aging. Thus, age-related dysfunctions of the antioxidant enzymesystem correlate with the type of adaptive behavior characteristic of animals.

Is High Oral Dose L-arginine Intake Effective in Leukoaraiosis? Preliminary Data, Study Protocol and Expert’s Opinion by Rocco Salvatore Calabro, Giuseppe Gervasi, Annalisa Baglieri, Anna Furnari, Silvia Marino, Placido Bramanti (170-177).
Background: Leukoraraiosis is worldwide considered as a part of the normal aging process, although it isstrongly associated with dementia and other disabilities. The pathogenesis of leukoaraiosis still has not been thoroughlyacknowledged, even though chronic ischemia with consequent arteriolosclerosis probably due to endothelial dysfunctionhas been suggested. Treatment focuses on prevention of lesion formation and progression by aggressive control of riskfactors, which should begin at an early age and continue on regular basis.Aim of our protocol is to evaluate the effect of long-term oral administration of high-dose L-arginine (6 g/day at least for24 months) on white matter lesions and neurological and cognitive functions.Materials and Methods: Patients affected by mild to moderate leukoaraiosis will be enrolled in the study. After a completeneurovascular assessment (i.e. accurate blood test examinations, Echocardiography, Doppler ultrasound of the neck andperipheral arteries), they will undergo MRI, specific neuropsychological tests and gait analysis. Patients will be evaluatedat baseline, at 6, 12, 18 and 24 month-follow up. Statistical Analysis will be performed using the software R. A significantlevel of P<0.05 will be set for all the tests.Preliminary Data: Two of the 4 patients currently enrolled in the study presented a mild improvement in cognitive function.Discussion: Because of its high prevalence in over-65-year-old subjects, we hypothesized that treatment with 6 gr of Larginine,as supplementary dietary option, could be helpful in patients affected by leukoaraiosis to improve the cognitiveand gait impairment often observed in these subjects (as demonstrated by the LADIS study).

Habitual physical activity and exercise are associated with the mortality rate and significantly contribute tothe prevention and/or amelioration of aging-related diseases including metabolic disorders, atherosclerosis, cancer, anddementia. Sirtuins are NAD+-dependent histone deacetylases that have emerged as key regulators of many functionsincluding metabolism, cell growth and apoptosis, as well as control of the aging process. Recent studies have demonstratedthat some types of exercise affect the expression and activity of sirtuins in several tissues. This review focuseson the effects of exercise on sirtuins and also their putative role with regard to the effects of exercise on preventing aging-related diseases.

Does a Physically Active Lifestyle Attenuate Decline in All Cognitive Functions in Old Age? by Soledad Ballesteros, Julia Mayas, Jose Manuel Reales (189-198).
In this study, the performance of a group of 20 physically active older adults was compared with that of agroup of 20 sedentary healthy older adults while performing a series of cognitive tasks. These tasks were designed to assessprocesses that deteriorate most with age, namely executive control (assessed with the Wisconsin Card Sorting Task)and processing speed (simple and choice reaction time tasks). A repetition priming task that does not decline with age, involvingattended and unattended picture outlines at encoding, was also included as a control task. The results show that aphysically active lifestyle has a positive influence on executive control, processing speed, and controlled processing. Asexpected, a physically active lifestyle did not enhance repetition priming for attended stimuli, nor did it produce primingfor unattended stimuli at encoding. Both groups exhibited robust priming for attended stimuli and no priming for unattendedones. Executive control functions are of vital importance for independent living in old age. These results havepractical implications for enhancing the cognitive processes that decline most in old age. Promoting a physically activelifestyle throughout adulthood could significantly reduce the decline of effortful executive control functions in old age.

Effects of Carnosine Plus Vitamin E and Betaine Treatments on Oxidative Stress in Some Tissues of Aged Rats by Jale Coban, Iknur Bingul, Kubra Yesil-M|zrak, Semra Dog ru-Abbasog lu, Serdar Oztezcan, Mujdat Uysal (199-205).
Oxidative stress plays an important role in aging. Effects of several antioxidants on age-related oxidative stresshave been investigated. Carnosine (CAR) and betaine have antioxidant actions. The combination of CAR with vitamin E(CAR+E) increases its antioxidant efficiency. We investigated the effects of CAR+E and betaine treatments on oxidativeand antioxidative status in liver, heart and brain tissues of aged rats. Experiments were carried out on young (5 months)and aged (22 months) male Wistar rats. Aged rats were given CAR (250 mg/kg; i.p.; 5 days per week) and vitamin E (200mg/kg; i.m.; twice per week) or betaine (1% w/v) for two months. Malondialdehyde (MDA) and diene conjugate (DC)levels and antioxidants were measured. MDA and DC levels were higher in tissues of aged rats than young rats. Glutathione(GSH) levels decreased in liver, but not heart and brain. There were no changes in vitamin E and vitamin C levelsand superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in tissuesof aged rats. CAR+E treatment was observed to decrease MDA and DC levels in tissues of aged rats. However, betainedecreased only hepatic MDA and DC levels. Both CAR+E and betaine increased hepatic GSH and vitamin E levels, butthese treatments did not affect antioxidant enzyme activities. These results suggest that CAR+E treatment seems to beuseful to decrease oxidative stress in liver, heart and brain tissues, but betaine is only effective in liver tissue of aged rats.

Biological Baseline of Joint Self-Repair Procedures by Valerio Di Nicola, Walter Pierpaoli (206-214).
Gel-Repairer is a biomaterial composed of Polydeoxyribonucleotides (Pdrn), Heat Shock Proteins (Hsps) and athickening substance. It works as a local mesenchymal stem cells (MSCs) stimulator, finally generating connective tissuerenewal.Our research is within the field of regenerative medicine and has historically built its foundation from the studies carriedout on non-vital amnion and placental membranes.Our end point is the activation and stimulation of the local mesenchymal stem cells (MSCs) for the structural recovery ofthe joint involved in the degenerative process.Since 2003, we have been applying the Gel Repairer over morethan 1200 patients, most of them elderly, affected by DegenerativeJoint Disease (DJD). After 10 years of clinical experience, the results are really impressive, including the absenceof toxicity, adverse reactions or side effects.Our clinical findings allowed the presentation of a clinical preliminary study performed on a large group of patients from2003 to 2009 and recently published [1].The following article is aimed at looking into the mechanism of action of the Joint Self-Repair procedure; furthermoresome new technical opportunities are presented on tissue engineering advances in this fast evolving sector.