Antioxidants in the diet have long been thought to confer some level of protection against the oxidative damage that is involved in the pathology of Alzheimer's disease as well as general cognitive decline in normal aging. Nevertheless, support for this hypothesis in the literature is equivocal. In the case of vitamin C (ascorbic acid) in particular, lack of consideration of some of the specific features of vitamin C metabolism has led to studies in which classification of participants according to vitamin C status is inaccurate, and the absence of critical information precludes the drawing of appropriate conclusions. Vitamin C levels in plasma are not always reported, and estimated daily intake from food diaries may not be accurate or reflect actual plasma values. The ability to transport ingested vitamin C from the intestines into blood is limited by the saturable sodium-dependent vitamin C transporter (SVCT1) and thus very high intakes and the use of supplements are often erroneously considered to be of greater benefit that they really are. The current review documents differences among the studies in terms of vitamin C status of participants. Overall, there is a large body of evidence that maintaining healthy vitamin C levels can have a protective function against age-related cognitive decline and Alzheimer's disease, but avoiding vitamin C deficiency is likely to be more beneficial than taking supplements on top of a normal, healthy diet.

OBJECTIVE:To study the effects of acupuncture on expression of heat shock protein (Hsp) 84 and 86, and brain ageing, in the senescence accelerated mouse prone 8 (SAMP8) model of Alzheimer's disease.

METHODS:7-month-old male senescence resistant mouse strain 1 (SAMR1) and SAMP8 mice were assigned to the following groups, with 15 animals in each group: SAMR1 control (Rc), SAMP8 control (Pc), SAMP8 acupuncture (Pa), SAMP8 sham-acupuncture (Psa). The Pa group was given acupuncture treatment once daily for 15 days. Neuromuscular coordination and cognitive function of the mice were evaluated by the tightrope test and Morris water maze test, respectively. The number of neurons in the CA1, CA3 and dentate gyrus (DG) regions of the hippocampus were measured. The levels of oxidative stress and protein carbonyl, mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus were detected.

RESULTS:Compared with the Rc group, in the Pc mice there was a lower success rate for the tightrope test, impaired cognitive abilities, a decline in neuron numbers, reduced levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), increased levels of superoxide anion and protein carbonyl, and decreased mRNA and protein levels of Hsp84 and Hsp86 (all P<0.05). After acupuncture treatment, the success rate for the tightrope test was elevated, cognitive function was improved, neuron numbers were enhanced, levels of SOD and GSH-Px were increased, levels of superoxide anion and protein carbonyl were decreased, and Hsp84 and Hsp86 mRNA and protein expression were increased in the Pa mice when compared with the Pc and Psa groups (all P<0.05).

CONCLUSION:Acupuncture may delay brain ageing in SAMP8 mice by reducing oxidative protein damage and promoting Hsp84 and Hsp86 expression.

To examine molecular events in hippocampus associated with aging and acupuncture effect, we employed cDNA arrays providing data of 588 genes to define transcriptional patterns. Male 8-month-old SAMP10 and its homologous SAMRl were selected and randomly divided into four groups: R1 control group (Rc), P10 control group (Pc), P10 acupuncture group (Pa) and P10 non-acupoint group (Pn). The points consisted Shanzhong (CV17), Zhongwan (CV12), Qihai (CV6), Zusanli (ST36) and Xuehai (SP10). In Pa, we found that points stimuli could completely or partly reverse some genes expression profiles in hippocampus with aging. Simultaneously, some genes not related with brain aging were affected by acupuncture as well. Meanwhile, non-acupoint had some effect on aging-unrelated genes expression and little or negative effect on aging-related genes. We verified array results with RT-PCR and Northern blotting for three genes which are related to oxidative damage closely, including Hsp84, Hsp86 and YB-1. In conclusion, acupuncture could be a potential intervention to retard molecular events with aging in mammals.

To examine molecular events in hippocampus associated with aging and acupuncture effect, we employed cDNA arrays providing data of 588 genes to define transcriptional patterns. Male 8-month-old SAMP10 and its homologous SAMRl were selected and randomly divided into four groups: R1 control group (Rc), P10 control group (Pc), P10 acupuncture group (Pa) and P10 non-acupoint group (Pn). The points consisted Shanzhong (CV17), Zhongwan (CV12), Qihai (CV6), Zusanli (ST36) and Xuehai (SP10). In Pa, we found that points stimuli could completely or partly reverse some genes expression profiles in hippocampus with aging. Simultaneously, some genes not related with brain aging were affected by acupuncture as well. Meanwhile, non-acupoint had some effect on aging-unrelated genes expression and little or negative effect on aging-related genes. We verified array results with RT-PCR and Northern blotting for three genes which are related to oxidative damage closely, including Hsp84, Hsp86 and YB-1. In conclusion, acupuncture could be a potential intervention to retard molecular events with aging in mammals.

Aging is associated with decline in cardiovascular, autonomic function, and brain-derived neurotropic factor (BDNF). Reports are scanty regarding whether yoga can improve age-related degenerative changes in healthy active men. This study is designed to appraise the role of yoga in improving age-related degenerative changes in cardiometabolic risk profile, autonomic function, stress, and BDNF. Healthy active males of three age groups (20-29, 30-39, and 40-49 years) were randomly assigned to practice yoga daily 1 h for 3 months. Significantly higher values of heart rate (HR), blood pressure (BP), load in heart (DoP), myocardial oxygen consumption (RPP), and total cholesterol (TC) were noted in senior age group. HR, BP, DoP, RPP, and TC decreased significantly following yogic practice. High frequency (HF), total power (TP), all time domain variables of heart rate variability (HRV), and skin conductance (SC) were significantly decreased with advancement of age. HF, TP, and time domain parameters of HRV and SC increased significantly following yogic practice. Higher levels of catecholamines and low frequency (LF) power of HRV was noted with advancement of age. Levels of catecholamines and LF significantly decreased following yogic practice. Cortisol and adrenocorticotropic hormone (ACTH) level raised in senior age group. BDNF, serotonin, and dopamine were low in higher age group. Significant decrement of cortisol; ACTH; and increment in serotonin, dopamine, and BDNF was noted following yogic practice. This study revealed that yogic practices might help in the prevention of age-related degeneration by changing cardiometabolic risk factors, autonomic function, and BDNF in healthy male.

Brain aging plays a pivotal role in senescence process and is related to cognition impairments and memory deficit and increases the risk of neurological disorders, but ideal therapeutic intervention has not been found. Here we report a dramatic effect of acupuncture, a powerful non-drug therapy way, on preventing changes in gene expression profiles with aging in senescence-accelerated mouse (SAMP10). We show that 48 genes in 588 genes examined display 2-fold or greater changes in gene expression with aging. However, we find that acupuncture can completely or partially prevent expression alterations of almost all these genes induced by aging. Our findings highlight a role of acupuncture as a potential intervention in anti-aging process and clinical therapy in future.

Brain aging plays a pivotal role in senescence process and is related to cognition impairments and memory deficit and increases the risk of neurological disorders, but ideal therapeutic intervention has not been found. Here we report a dramatic effect of acupuncture, a powerful non-drug therapy way, on preventing changes in gene expression profiles with aging in senescence-accelerated mouse (SAMP10). We show that 48 genes in 588 genes examined display 2-fold or greater changes in gene expression with aging. However, we find that acupuncture can completely or partially prevent expression alterations of almost all these genes induced by aging. Our findings highlight a role of acupuncture as a potential intervention in anti-aging process and clinical therapy in future.

The present study explored the effects of swimming training and grape seed proanthocyanidin extract (GSPE) on neuronal survival in the hippocampus (HC) of middle-aged rats along with oxidative stress (OS) parameters. Further, the bioavailability of the GSPE, catechin, epicatechin and gallic acid were measured in the HC and plasma. Male Wistar rats were grouped into: sedentary control, SE-C; swimming trained, SW-T; SE-C, supplemented sedentary, SE-C(PA) and swimming trainees, SW-T(PA). The supplement was a daily dose of 400mg GSPE/kg body weight. Swimming training lasted for 2h/day and for 14weeks. Glutathione level was increased in response to single and combined interventions in the middle-aged rats. Adult trainees showed increased glutathione peroxidase activity unlike middle-aged wherein increase was seen in SE-C(PA) alone. Lowered catalase activity with age in the HC increased in response to the combined interventions although single interventions were also effective. HC from both ages showed decrease in lipid peroxidation and hydrogen peroxide levels in response to the interventions. GSPE constituents were seen in the HC of swimming trained middle-aged and adult rats. The study suggests that combined intervention is effective in decreasing LPO and HOgeneration in the HC. Further, the neuronal numbers and planimetric volumes of CA1 pyramidal layer was significantly reduced in middle-aged rats compared to adults. Interestingly, both interventions enhanced the numbers and volumes in adult and middle-aged rats. Thus, age-associated decrease in CA1 neurons could be restored by both the interventions. The results of the present study will help in developing effective therapies for age-associated degenerative changes and cognitive deficits.

BACKGROUND:Mild cognitive impairment (MCI) is a phase in cognitive decline when it is still possible to intervene to reverse the decline. Cognitive stimulation delivered through psychosocial interventions provides both psychological intervention and social stimulation to improve cognition. A pilot open-label parallel-arms randomized controlled trial was undertaken to examine the effects of art therapy (AT) and music reminiscence activity (MRA) compared to the control, on the primary outcome of neurocognitive domain assessments in elderly people with MCI.

METHODS:Community-living elderly people with MCI (Petersen's criteria), assessed for study eligibility, were randomized using a web-based system with equal allocation to two intervention arms: AT (guided viewing of art pieces and production of visual arts) and MRA (listening, and recalling memories related to music) and a control arm (standard care without any intervention). Interventions were led by trained therapists weekly for 3 months, then fortnightly for 6 months. Neurocognitive domains (mean of memory, attention, and visuo-spatial abilities standardized scores), psychological wellbeing (subsyndromal depression and anxiety) and telomere length as a biological marker of cellular ageing, were assessed by intervention-blinded assessors at baseline, 3 months and 9 months.

RESULTS:In total, 250 people were screened and 68 were randomized and included in the analysis. In the AT arm, neurocognitive domains improved compared to the control arm at 3 months (mean difference (d) = 0.40; 90% CI 0.126, 0.679) and were sustained at 9 months (d = 0.31; 90% CI 0.068, 0.548). There wassome improvement in depression and anxiety at 3 and 9 months and in telomere length at 9 months, but this was not significant. Similar improvements were observed in the MRA arm over the control arm, but they were not significant. There were no intervention-related adverse effects.

CONCLUSIONS:Art therapy delivered by trained staff as"art as therapy"and"art psychotherapy"may have been the significant contributor to cognitive improvements. The findings support cognitive stimulation for elderly people with cognitive decline and signal the need for larger studies and further investigation of carefully designed psycho-social interventions for this group.

TRIAL REGISTRATION:Clinical Trials.gov, NCT02854085 . Registered on 7 July 2016.

Production of new neurons from stem cells is important for cognitive function, and the reduction of neurogenesis in the aging brain may contribute to the accumulation of age-related cognitive deficits. Restriction of calorie intake and prolonged treatment with rapamycin have been shown to extend the lifespan of animals and delay the onset of the age-related decline in tissue and organ function. Using a reporter line in which neural stem and progenitor cells are marked by the expression of green fluorescent protein (GFP), we examined the effect of prolonged exposure to calorie restriction (CR) or rapamycin on hippocampal neural stem and progenitor cell proliferation in aging mice. We showed that CR increased the number of dividing cells in the dentate gyrus of female mice. The majority of these cells corresponded to nestin-GFP-expressing neural stem or progenitor cells; however, this increased proliferative activity of stem and progenitor cells did not result in a significant increase in the number of doublecortin-positive newborn neurons. Our results suggest that restricted calorie intake may increase the number of divisions that neural stem and progenitor cells undergo in the aging brain of females.

The brain can generate new neurons from neural stem cells throughout life. However, the capacity for neurogenesis declines with age, reducing the potential for learning and repair. We explored the effects of calorie restriction, an established anti-aging intervention, on neural stem cells in the subventricular zone of young and aged mice. Calorie restriction transiently enhanced proliferation of neural progenitor cells in young, but not aged mice. However, calorie restriction prevented the age-related loss of neurogenesis in the aged brain. Calorie-restricted mice showed enhanced olfactory memory compared withfed controls, suggesting that calorie restriction can produce functional improvements in the aged brain. Calorie restriction also mitigated the age-related activation of microglia and subsequent increase in pro-inflammatory cytokines. Likewise, calorie restriction prevented increases in senescent cells normally observed in the subventricular zone in aged mice, further protecting this neurogenic niche from pro-inflammatory signals. Together, these data suggest that calorie restriction protects the subventricular zone microenvironment from age-related inflammation, thereby preserving neurogenesis into old age.

 Oxidative mitochondrial decay is a major contributor to aging. Some of this decay can be reversed in old rats by feeding them normal mitochondrial metabolites, acetylcarnitine (ALC) and lipoic acid (LA), at high levels. Feeding the substrate ALC with LA, a mitochondrial antioxidant, restores the velocity of the reaction (K(m)) for ALC transferase and mitochondrial function. The principle appears to be that, with age, increased oxidative damage to protein causes a deformation of structure of key enzymes with a consequent lessening of affinity (K(m)) for the enzyme substrate. The effect of age on the enzyme-binding affinity can be mimicked by reacting it with malondialdehyde (a lipid peroxidation product that increases with age). In old rats (vs. young rats), mitochondrial membrane potential, cardiolipin level, respiratory control ratio, and cellular O(2) uptake are lower; oxidants/O(2), neuron RNA oxidation, and mutagenic aldehydes from lipid peroxidation are higher. Ambulatory activity and cognition decline with age. Feeding old rats ALC with LA for a few weeks restores mitochondrial function; lowers oxidants, neuron RNA oxidation, and mutagenic aldehydes; and increases rat ambulatory activity and cognition (as assayed with the Skinner box and Morris water maze). A recent meta-analysis of 21 double-blind clinical trials of ALC in the treatment of mild cognitive impairment and mild Alzheimer's disease showed significant efficacy vs. placebo. A meta-analysis of 4 clinical trials of LA for treatment of neuropathic deficits in diabetes showed significant efficacy vs. placebo.

Preventing or postponing the onset of Alzheimer's disease (AD) and delaying or slowing its progression would lead to a consequent improvement of health status and quality of life in older age. Elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggests a possible association between fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA; in particular, n-3 PUFA) and a reduced risk of cognitive decline and dementia. Poorer cognitive function and an increased risk of vascular dementia (VaD) were found to be associated with a lower consumption of milk or dairy products. However, the consumption of whole-fat dairy products may be associated with cognitive decline in the elderly. Light-to-moderate alcohol use may be associated with a reduced risk of incident dementia and AD, while for VaD, cognitive decline and predementia syndromes, the current evidence is only suggestive of a protective effect. The limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supports a protective role of these macronutrients against cognitive decline, dementia and AD. Only recently, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micro- and macro-nutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD and a decreased all-cause mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk of AD, but also of predementia syndromes and their progression to overt dementia. Based on the current evidence concerning these factors, no definitive dietary recommendations are possible. However, following dietary advice for lowering the risk of cardiovascular and metabolic disorders, high levels of consumption of fats from fish, vegetable oils, nonstarchy vegetables, low glycemic index fruits and a diet low in foods with added sugars and with moderate wine intake should be encouraged. Hopefully this will open new opportunities for the prevention and management of dementia and AD.

Objectives:We aimed to examine the effects of various leisure activities on cognitive impairment in young-old (aged 65-74 years) and old-old (aged≥ 75 years) adults.

Methods:In total, 10,279 elderly Korean individuals from the 2014 Korean National Survey on Older Adults' cohort were enrolled in our study. Cognitive impairment was assessed using the standardized score of the Mini-Mental State Examination for Dementia Screening, whereas leisure activities were recorded via self-reporting of the extent and type of leisure activity the subjects involved in over the past year. Multivariate logistic regression was used to assess the effect of leisure activities on cognitive impairment, while controlling for potential covariates.

Results:The subjects were more likely to participate in cognitive activities than in non-exercise physical activities. After controlling for selected covariates, involvement in cognitive activities was found to be a significant predictor of cognitive impairment in both the groups, whereas involvement in non-exercise physical activities was not a predictor of cognitive impairment in individuals aged≥ 75 years. Moreover, depressive symptoms, rural residence, and hearing difficulties were common predictors of cognitive impairment among elderly-Korean-individuals.

Conclusion:Leisure activity involvement may help delay cognitive impairment, which is often concomitant with aging. Hence, an early intervention service may significantly benefit both young-old and old-old individuals.

Aging is one of the major factors which decline cognitive function associated with hippo- campus and prefrontal cortex, so it is an urgent issue to develop the practical treatment for aging brain. Since many researchers show that physical exercise can increase hippocampal neurogenesis and gray matter volume of prefrontal cortex, physical exercise is a potential candidate for preventing cognitive decline. Recently, we have reported that mild intensity exercise training enhances neurogenesis in rodents. In addition, we found long term inter- vention of mild exercise has beneficial effects on prefrontal gray matter volume and cognitive function in older adults. Based on these facts, mild exercise could be optimal strategy for anti-aging of brain.

OBJECTIVE:To observe the influence of moxibustion on the cyclin and cellular proliferin of the cerebral cortex in senile mice so as to explore its underlying mechanism in delaying aging.

METHODS:Sixty male mice were randomly and equally divided into control, model, moxibustion of "Zusanli" (ST 36) and "Xuanzhong" (GB 39, M-ST 36-GB 39), moxibustion of "Baihui" (GV 20) and "Guanyuan" (CV 4,M-GV 20-COV 4) ,and medication groups. The aging model was established by subcutaneous injection of D-galactose for 42 days. Moxibustion was applied to ST 36, GB 39, GV 20 and CV 4 separately for 3 moxa-cones, once every other day for one month. The expression of cell cycle protein P 16 and retinoblastoma (pRb), and c-fos protein in the cerebral cortex tissue of the senile mice were detected by immunohistochemistry.

RESULTS:Compared with control group, the number of P16 immunoreaction (IR) positive neurons in the cerebral cortex increased significantly in the model group (P<0.01), and those of cortical pRb and c-fos IR-positive neurons decreased considerably in model group (P<0.01). In comparison with the model group, the number of cortical P 16 IR-positive neurons reduced significantly in M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P<0.01), and those of cortical pRb and c-fos IR-positive neurons increased remarkably in M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P<0.01, P<0.05). No significant differences were found in the aforementioned 3 indexes among M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P>0.05).

CONCLUSION:Moxibustion of ST 36-GB 39 and GV 20-CV 4 can down-regulate the P 16 expression,and up-regulate pRb and c-fos protein expression in the cerebral cortex of senile mice, which possibly contributes to its effect in delaying aging.

Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time where aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a constantly slower rate of brain aging throughout life.

In the present article, we provide a brief review of current knowledge regarding the effects induced by physical exercise on hippocampus. Research involving animals and humans supports the view that physical exercise, enhancing hippocampal neurogenesis and function, improves cognition, and regulates mood. These beneficial effects depend on the contribute of more factors including the enhancement of vascularization and upregulation of growth factors. Among these, the BDNF seems to play a significant role. Another putative factor that might contribute to beneficial effects of exercise is the orexin-A. In support of this hypothesis there are the following observations: (1) orexin-A enhances hippocampal neurogenesis and function and (2) the levels of orexin-A increase with physical exercise. The beneficial effects of exercise may represent an important resource to hinder the cognitive decline associated with the aging-related hippocampal deterioration and ameliorate depressive symptoms.

The hippocampus plays an important role in learning and memory. Unlike most brain cells (whose numbers are fixed before birth), thousands of new hippocampal granule cells continue to be generated every day throughout adult life. This article is protected by copyright. All rights reserved.

Aging and mild cognitive impairment (MCI) are accompanied by decline of cognitive functions. Meanwhile, the most common form of dementia is Alzheimer's disease (AD), which is characterized by loss of memory and other intellectual abilities serious to make difficulties for patients in their daily life. MCI is a transition period between normal aging and dementia, which has been used for early detection of emerging dementia. It converts to dementia with an annual rate of 5-15% as compared to normal aging with 1% rate. Small decreases in the conversion rate of MCI to AD might significantly reduce the prevalence of dementia. Thus, it is important to intervene at the preclinical stage. Since there are still no effective drugs to treat AD, non-drug intervention is crucial for the prevention and treatment of cognitive decline in aging and MCI populations. Previous studies have found some cognitive brain networks disrupted in aging and MCI population, and physical exercise (PE) could effectively remediate the function of these brain networks. Understanding the exercise-related mechanisms is crucial to design efficient and effective PE programs for treatment/intervention of cognitive decline. In this review, we provide an overview of the neuroimaging studies on physical training in normal aging and MCI to identify the potential mechanisms underlying current physical training procedures. Studies of functional magnetic resonance imaging, electroencephalography, magnetoencephalography and positron emission tomography on brain networks were all included. Based on our review, the default mode network, fronto-parietal network and fronto-executive network are probably the three most valuable targets for efficiency evaluation of interventions.