AGE最新文献

High consumption of fruits and vegetables has been associated with reduced risk of debilitating diseases and improved cognition in aged populations. These beneficial effects have been attributed to the phytochemicals found in fruits and vegetables, which have previously been shown to be anti-inflammatory and modulate autophagy. Tart cherries contain a variety of potentially beneficial phytochemicals; however, little research has been done to investigate the effects of tart cherry on the aging brain. Therefore, the purpose of this study was to determine if tart cherry supplementation can improve cognitive and motor function of aged rats via modulation of inflammation and autophagy in the brain. Thirty 19-month-old male Fischer 344 rats were weight-matched and assigned to receive either a control diet or a diet supplemented with 2 % Montmorency tart cherry. After 6 weeks on the diet, rats were given a battery of behavioral tests to assess for strength, stamina, balance, and coordination, as well as learning and working memory. Although no significant effects were observed on tests of motor performance, tart cherry improved working memory of aged rats. Following behavioral testing, the hippocampus was collected for western/densitometric analysis of inflammatory (GFAP, NOX-2, and COX-2) and autophagy (phosphorylated mTOR, Beclin 1, and p62/SQSTM) markers. Tart cherry supplementation significantly reduced inflammatory markers and improved autophagy function. Daily consumption of tart cherry reduced age-associated inflammation and promoted protein/cellular homeostasis in the hippocampus, along with improvements in working memory. Therefore, addition of tart cherry to the diet may promote healthy aging and/or delay the onset of neurodegenerative diseases.

Older individuals who exercise regularly exhibit greater resistance to oxidative stress than their sedentary peers, suggesting that exercise can modify age-associated loss of resistance to oxidative stress. However, we recently demonstrated that a single bout of exercise confers protection against a subsequent oxidative challenge in young, but not older adults. We therefore hypothesized that repeated bouts of exercise would be needed to increase resistance to an oxidative challenge in sedentary older middle-aged adults. Sedentary older middle-aged men and women (50-63 years, n = 11) participated in an 8-week exercise intervention. Maximal oxygen consumption was measured before and after the intervention. The exercise intervention consisted of three sessions per week, for 45 min at an intensity corresponding to 70-85 % maximal heart rate (HR_max). Resistance to oxidative stress was measured by F₂-isoprostane response to a forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R trial before and after the exercise intervention. The intervention elicited a significant increase in maximal oxygen consumption (VO_2max) (P < 0.0001). Baseline levels of F₂-isoprostanes pre- and post-intervention did not differ, but the F₂-isoprostane response to the I/R trial was significantly lower following the exercise intervention (time-by-trial interaction, P = 0.043). Individual improvements in aerobic fitness were associated with greater improvements in the F₂-isoprostane response (r = -0.761, P = 0.011), further supporting the role of aerobic fitness in resistance to oxidative stress. These data demonstrate that regular exercise with improved fitness leads to increased resistance to oxidative stress in older middle-aged adults and that this measure is modifiable in previously sedentary individuals.

Elderly people are characterized by a high prevalence of falls and sarcopenia. However, the relationship among Tinetti mobility test (TMT) score, a powerful tool to detect elderly people at risk of falls, and sarcopenia is still not thoroughly investigated. Thus, to determine the relationship between TMT score and muscle mass and strength, 337 elderly participants (mean age 77.1 ± 6.9 years) admitted to comprehensive geriatric assessment were enrolled. TMT score, muscle mass by bioimpedentiometer, and muscle strength by grip strength were evaluated. Muscle mass progressively decreased as TMT score decreased (from 15.3 ± 3.7 to 8.8 ± 1.8 kg/m²; p for trend <0.001). Similarly, muscle strength decreased progressively as Tinetti score decreased (from 34.7 ± 8.0 to 23.7 ± 8.7 kg; p for trend 0.001). Linear regression analysis demonstrated that TMT score is linearly related with muscle mass (y = 4.5x + 0.4, r = 0.61; p < 0.01) and strength (y = 14.0x + 0.8, r = 0.53; p < 0.01). Multivariate analysis confirms the strong relationship between the TMT score and muscle mass (r = 0.48, p = 0.024) and strength (r = 0.39, p = 0.046). The present study indicates that TMT score is significantly related to muscle mass and strength in non-institutionalized elderly participants. This evidence suggests that TMT score, together with evaluation of muscle mass and strength, may identify sarcopenic elderly participants at high risk of falls.

Statins, such as simvastatin, and ACE inhibitors (ACEis), such as ramipril, are standard therapies for the prevention and treatment of cardiovascular diseases. These types of drugs are commonly administered together. More recently, angiotensin II type 1 receptor (AT1R) antagonists, such as candesartan cilexetil (candesartan), have been used in the place of, or in combination with, ACEis. Here, we investigated the effects of simvastatin and ramipril single and combination therapy, and candesartan treatment on the lifespan of isocalorically fed, long-lived, B6C3F1 mice. Males were used for their relative endocrine simplicity and to minimize animal usage. The drugs were administered daily in food. The simvastatin and ramipril combination therapy significantly increased the mean and median lifespan by 9 %. In contrast, simvastatin, ramipril, or candesartan monotherapy was ineffective. All groups consumed the same number of calories. Simvastatin, alone or administered with ramipril, decreased body weight without changing caloric consumption, suggesting it may alter energy utilization in mice. Combination therapy elevated serum triglyceride and glucose levels, consistent with altered energy homeostasis. Few significant or consistent differences were found in mortality-associated pathologies among the groups. Simvastatin treatment did not reduce normal serum cholesterol or lipid levels in these mice, suggesting that the longevity effects may stem from the pleiotropic, non-cholesterol-related, effects of statins. Together, the results suggest that statins and ACEis together may enhance mouse longevity. Statins and ACE inhibitors are generally well-tolerated, and in combination, they have been shown to increase the lifespan of normotensive, normocholesterolemic humans.

Improving healthspan, defined as the period where organisms live without frailty and/or disease, is a major goal of biomedical research. While healthspan measures in people are relatively easy to identify, developing robust markers of healthspan in model organisms has proven challenging. Studies using the nematode Caenorhabditis elegans have provided vital information on the basic mechanisms of aging; however, worm health is difficult to define, and the impact of interventions that increase lifespan on worm healthspan has been controversial. Here, we describe a marker of population healthspan in C. elegans that we term age-associated vulval integrity defects, or Avid, frequently described elsewhere as rupture or exploding. We connect the presence of this phenotype with temperature, reproduction, diet, and longevity. Our results show that Avid occurs in post-reproductive worms under common laboratory conditions at a frequency that correlates negatively with temperature; Avid is rare in worms kept at 25 °C and more frequent in worms kept at 15 °C. We describe the kinetics of Avid, link the phenotype to oocyte production, and describe how Avid involves the ejection of worm proteins and/or internal organ(s) from the vulva. Finally, we find that Avid is preventable by removing worms from food, suggesting that Avid results from the intake, digestion, and/or absorption of food. Our results show that Avid is a significant cause of death in worm populations maintained under laboratory conditions and that its prevention often correlates with worm longevity. We propose that Avid is a powerful marker of worm healthspan whose underlying molecular mechanisms may be conserved.

Apolipoprotein E (APOE) ε4 allele and education have been reported to affect the cognitive function in young-old adults. However, the effects and interactions of the ε4 allele and education on cognitive function in very old age, particularly in centenarians, are not well known. We studied 542 Japanese centenarians. Using the data in total of 452 participants (74 men and 378 women, mean age 103.6 ± 3.2 years) who were genotyped and assessed cognitive function with the Mini-Mental States Examination (MMSE), we examined the effects and interactions of the ε4 allele and education on the MMSE score. First, we coded education as three levels: low, middle, and high based on the formal educational levels (analysis 1). Second, to clarify the modifying effect of education, we adopted a new coding for education into two levels, considering a periodical background (around 1900) of gender differences in educational attainments (analysis 2). In analysis 1, the main effects of the ε4 allele and education on the MMSE score were significant after adjusting for age. Further, there was a significant three-way interaction effect between the ε4 allele, education, and gender on the MMSE. Analysis 2 showed that the modifying effect of the ε4 allele by education was observed only in women with the ε4 allele. These findings suggest that both the APOE ε4 allele and education appear to be associated with cognitive function even in centenarians, but the interaction between the ε4 allele and education might depend on gender in this cohort.

Plantar flexion strength and balance ability are considered to be crucial for avoiding falls. However, no clear relationship has been established between these two factors in elderly population. This study aimed to examine the association between plantar flexion strength and balance performance in elderly men and women. Forty-three men and 35 women aged over 65 years performed isometric plantar flexion as fast and hard as possible. From the time-torque curve, the rate of torque development in time intervals of 30, 50, 100, 150, and 200 ms from the onset of contraction was determined and normalized to peak torque. In addition, the center of pressure displacement during single-leg standing was calculated and normalized to height. When the data were collapsed over sexes, the normalized rate of torque development was negatively correlated with the normalized center of pressure displacement, except for the time interval of 200 ms. By sex, regardless of the time interval, there was a negative correlation between the normalized rate of torque development and the normalized center of pressure displacement in the elderly men but not in the elderly women. No correlation was seen between the peak torque and normalized center of pressure displacement in either pooled or separated data. The findings suggest that the capability of rapid force production rather than maximal force production of the plantar flexion is important for balance ability in elderly men, but this capability may not be relevant in elderly women.