Abstract: With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this cross-sectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones [insulin-like growth factor-1 (IGF-1), free testosterone (males only)] and catabolic markers [inflammatory markers (interleukin-6, C-reactive protein) and myostatin]. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR = 5.71, 95 % CI 1.13–28.84.44, p = 0.035) while higher but acceptable range serum triglyceride was protective in men (OR = 0.05, 95 % CI 0.00–0.52, p = 0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR = 1.11, 95 % CI 1.00–1.24, p = 0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1 % decline in odds of sarcopenia in women (p = 0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults.

Abstract: Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (<35 years) and 20 elderly (50–80 year) healthy, male non-smokers consumed either a CF-containing drink (450 mg CF) or nutrient-matched, CF-free control drink bi-daily for 14 days. The primary endpoint was endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints included cardiac output, vascular stiffness, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Following 2 weeks of CF intake, FMD improved in young (6.1 ± 0.7 vs. 7.6 ± 0.7 %, p < 0.001) and elderly (4.9 ± 0.6 vs. 6.3 ± 0.9 %, p < 0.001). Secondary outcomes demonstrated in both groups that CF intake decreased pulse wave velocity and lowered total peripheral resistance, and increased arteriolar and microvascular vasodilator capacity, red cell deformability, and diastolic blood pressure, while cardiac output remained affected. In the elderly, baseline systolic blood pressure was elevated, driven by an arterial-stiffness-related augmentation. CF intake decreased aortic augmentation index (−9 %) and thus systolic blood pressure (−7 mmHg; Clinicaltrials.gov: NCT01639781). CF intake reverses age-related burden of cardiovascular risk in healthy elderly, highlighting the potential of dietary flavanols to maintain cardiovascular health.

Abstract: Frailty is one of the geriatric syndromes and has an important relationship with mortality and morbidity. The aim of this study is to present the characteristics, prevalence, and related factors of frailty in older adults in our country. The study included 1126 individuals over 65 years of age from 13 centers. Frailty was evaluated using the Fried Frailty criteria, and patients were grouped as “frail,” “pre-frail,” and “non-frail.” Nutritional status was assessed with “Mini Nutritional Test,” psychological status with the “Center for Epidemiological Studies Depression Scale-CES-D,” and additional diseases with the “Charlson Comorbidity index.” Approximately 66.5 % of the participants were between 65 and 74 years of age and 65.7 % were women. Some 39.2 and 43.3 % of the participants were rated as frail and pre-frail, respectively. The multinomial logistic regression analysis was used to determine the factors associated with frailty. It was observed that age, female gender, low education level, being a housewife, living with the family, being sedentary, presence of an additional disease, using 4 or more drugs/day, avoiding to go outside, at least one visit to any emergency department within the past year, hospitalization within the past year, non-functional ambulation, and malnutrition increased the risk of frailty (p < 0.05). Establishing the factors associated with frailty is highly important for both clinical practice and national economy. This is the first study on this subject in our country and will provide guidance in determining treatment strategies.

Abstract: Restricted dietary intakes of protein or essential amino acids tend to slow aging and boost lifespan in rodents, presumably because they downregulate IGF-I/Akt/mTORC1 signaling that acts as a pacesetter for aging and promotes cancer induction. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) III cohort has revealed that relatively low protein intakes in mid-life (under 10 % of calories) are indeed associated with decreased subsequent risk for mortality. However, in those over 65 at baseline, such low protein intakes were associated with increased risk for mortality. This finding accords well with other epidemiology correlating relatively high protein intakes with lower risk for loss of lean mass and bone density in the elderly. Increased efficiency of protein translation reflecting increased leucine intake and consequent greater mTORC1 activity may play a role in this effect; however, at present there is little solid evidence that leucine supplementation provides important long-term benefits to the elderly. Aside from its potential pro-anabolic impact, higher dietary protein intakes may protect the elderly in another way-by providing increased amino acid substrate for synthesis of key protective factors. There is growing evidence, in both rodents and humans, that glutathione synthesis declines with increasing age, likely reflecting diminished function of Nrf2-dependent inductive mechanisms that boost expression of glutamate cysteine ligase (GCL), rate-limiting for glutathione synthesis. Intracellular glutathione blunts the negative impact of reactive oxygen species (ROS) on cell health and functions both by acting as an oxidant scavenger and by opposing the pro-inflammatory influence of hydrogen peroxide on cell signaling. Fortunately, since GCL's K m for cysteine is close to intracellular cysteine levels, increased intakes of cysteine-achieved from whole proteins or via supplementation with N-acetylcysteine (NAC)-can achieve a compensatory increase in glutathione synthesis, such that more youthful tissue levels of this compound can be restored. Supplementation with phase 2 inducers-such as lipoic acid-can likewise increase glutathione levels by promoting increased GCL expression. In aging humans and/or rodents, NAC supplementation has exerted favorable effects on vascular health, muscle strength, bone density, cell-mediated immunity, markers of systemic inflammation, preservation of cognitive function, progression of neurodegeneration, and the clinical course of influenza-effects which could be expected to lessen mortality and stave off frailty. Hence, greater cysteine availability may explain much of the favorable impact of higher protein intakes on mortality and frailty risk in the elderly, and joint supplementation with NAC and lipoic acid could be notably protective in the elderly, particularly in those who follow plant-based diets relatively low in protein. It is less clear whether the lower arginine intake associated with low-protein diets has an adverse impact on vascular health.

Abstract: The purpose of this study was to analyze the effects of a progressive resistance training (RT) program on C-reactive protein (CRP), blood glucose (GLU), and lipid profile in older women with differing levels of RT experience. Sixty-five older women (68.9 ± 6.1 years, 67.1 ± 13.1 kg) were separated according to RT experience: an advanced group composed by 35 participants who previously carried out 24 weeks of RT and a novice group composed by 30 participants without previous experience in RT (n = 30). Both groups performed a RT program comprised of eight exercises targeting all the major muscles. Training was carried out 3 days/week for 8 weeks. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), GLU, and CRP concentrations were determined pre- and post- intervention after 12 h fasting. A significant group by time interaction (P < 0.05) for the TC (novice = -1.9% vs. advanced = 1.0%), and CRP (novice = -22.9% vs. advanced = -54.5%) was observed. A main effect of time (P < 0.05) was identified for the GLU (novice = -2.6% vs. advanced = -6.6%), TG (novice = -12.9% vs. advanced = -5.7%), HDL-C (novice = +6.7% vs. advanced = +2.6%), and LDL-C (novice = -34.0% vs. advanced = -25.4%). These results suggest that RT improves the metabolic profile of older women and that training for a longer period of time seems to produce more pronounced reductions mainly on CRP.

Abstract: Regular physical exercise has been shown to be one of the most important lifestyle influences on improving functional performance, decreasing morbidity and all causes of mortality among older people. However, it is known that acute physical exercise may induce an increase in oxidative stress and oxidative damage in several structures, including DNA. Considering this, the purpose of this study was to identify the effects of 16 weeks of combined physical exercise in DNA damage and repair capacity in lymphocytes. In addition, we aimed to investigate the role of oxidative stress involved in those changes. Fifty-seven healthy men (40 to 74 years) were enrolled in this study. The sample was divided into two groups: the experimental group (EG), composed of 31 individuals, submitted to 16 weeks of combined physical exercise training; and the control group (CG), composed of 26 individuals, who did not undergo any specifically orientated physical activity. We observed an improvement of overall physical performance in the EG, after the physical exercise training. A significant decrease in DNA strand breaks and FPG-sensitive sites was found after the physical exercise training, with no significant changes in 8-oxoguanine DNA glycosylase enzyme activity. An increase was observed in antioxidant activity, and a decrease was found in lipid peroxidation levels after physical exercise training. These results suggest that physical exercise training induces protective effects against DNA damage in lymphocytes possibly related to the increase in antioxidant capacity.

Abstract: This study was designed to compare the effects of linear periodization (LP) and undulating periodization (UP) on functional capacity, neuromuscular function, body composition, and cytokines in elderly sedentary women We also aimed to identify the presence of high responders (HR), medium responders (MR), and low responders (LR) for irisin, interleukin-1 beta (IL-1β), toll-like receptor-4 (TLR-4), and brain-derived neurotrophic factor (BDNF) to resistance training (RT) Forty-nine elderly women were assigned to a control group, LP, and UP scheme Functional capacity, body composition, maximal strength, irisin, TLR-4, BDNF, and IL-1β were evaluated Both periodization models were effective in improving 45° leg press 1RM, chair-stand, arm curl, and time-up and go tests, with no significant differences in body composition and cytokines Furthermore, HR, MR, and LR were identified for irisin, IL-1β, TLR-4, and BDNF, with differences between groups and moments This study provides evidence that both periodization models were effective in improving functional capacity and neuromuscular function, with no effect on body composition and cytokines (probably as a consequence of the different responsiveness) Furthermore, for the first time, HR, MR, and LR were identified for irisin, IL1-β, TLR-4, and BDNF in response to RT

Abstract: The manner and extent to which voice amplitude and frequency control mechanisms change with age is not well understood. The related question of whether the assessment of one's own voice evolves with age, concomitant with the acoustical changes that the voice undergoes, also remains unanswered. In the present study, we characterized the aging of voice production mechanisms (amplitude, frequency), compared the aging voice in different experimental contexts (vowel utterance, connected speech) and examined the relationship between voice self-assessment and age-related voice acoustical changes. Eighty healthy adults (20 to 75 years old) participated in the study, which involved computation of several acoustical measures of voice (including measures of fundamental frequency, voice amplitude, and stability) as well as self-assessments of voice. Because depression is frequent in older adults, depression and anxiety scores were also measured. As was expected, analyses revealed age effects on most acoustical measures. However, there was no interaction between age and the ability to produce high/low voice amplitude/frequency, suggesting that voice amplitude and frequency control mechanisms are preserved in aging. Multiple mediation analyses demonstrated that the relationship between age and voice self-assessment was moderated by depression and anxiety scores. Taken together, these results reveal that while voice production undergoes important changes throughout aging, the ability to increase/decrease the amplitude and frequency of voice are preserved, at least within the age range studied, and that depression and anxiety scores have a stronger impact on perceived voice quality than acoustical changes themselves.

Abstract: Immunosenescence results from a continuous deterioration of immune responses resulting in a decreased response to vaccines A well-described age-related alteration of the immune system is the decrease of de novo generation of T and B cells In addition, the accumulation of memory cells and loss of diversity in antigen specificities resulting from a lifetime of exposure to pathogens has also been described However, the effect of aging on subsets of γδTCR(+) T cells and Tregs has been poorly described, and the efficacy of the recall response to common persistent infections in the elderly remains obscure Here, we investigated alterations in the subpopulations of the B and T cells among 24 healthy young (aged 19-30) and 26 healthy elderly (aged 53-67) individuals The analysis was performed by flow cytometry using freshly collected peripheral blood γδTCR(+) T cells were overall decreased, while CD4(+)CD8(-) cells among γδTCR(+) T cells were increased in the elderly Helios(+)Foxp3(+) and Helios(-)Foxp3(+) Treg cells were unaffected with age Recent thymic emigrants, based on CD31 expression, were decreased among the Helios(+)Foxp3(+), but not the Helios(-)Foxp3(+) cell populations We observed a decrease in Adenovirus-specific CD4(+) and CD8(+) T cells and an increase in CMV-specific CD4(+) T cells in the elderly Similarly, INFγ(+)TNFα(+) double-positive cells were decreased among activated T cells after Adenovirus stimulation but increased after CMV stimulation The data presented here indicate that γδTCR(+) T cells might stabilize B cells, and functional senescence might dominate at higher ages than those studied here

Abstract: Quantification of key outcome measures in animal models of aging is an important step preceding intervention testing. One such measure- ment, skeletal muscle power generation (force * velocity), is critical for dynamic movement. Prior research focused on maximum power (Pmax), which occurs around 30-40 % of maximum load. However, movement occurs over the entire load range. Thus, the primary purpose of this study was to determine the effect of age on power gen- eration during concentric contractions in the exten- sor digitorum longus (EDL) and soleus muscles over the load range from 10 to 90 % of peak isometric tetanic force (P0). Adult, old, and elderly male C57BL/6 mice were examined for contractile function (6-7 months old, 100 % survival; ~24 months, 75 %; and ~28 months, 50 % P0). The shape of the force-velocity curve also changed with age (a/P0 increased). In addi- tion, there were prolonged contraction times to maximum force and shifts in the distribution of the myosin light and heavy chain isoforms in the EDL. The results demonstrate that age-associated difficulty in movement during challenging tasks is likely due, in addition to overall reduced force output, to an accelerated deterioration of power production and contractile velocity under heavily loaded conditions.

Abstract: The objective of this study was to evaluate the effects of steroid anabolic androgenic hormones use on lean mass gain in elderly men through a systematic review with a meta-analysis of randomized controlled studies. We systematically searched PubMed database until 4th October 2013. We included randomized placebo-controlled trials (RCT) that studied testosterone replacement therapy in men over 60 years of age, with total testosterone levels ≤550 ng/dl, observing gains in weight, lean mass tissue and fat mass as outcome. We excluded duplicated studies, studies which mixed men and women, and studies using weak androgens such as dehydroepiandrosterone or androstenedione. The initial search yielded 2681 articles, of which 26 were selected for full text analysis. In the end, 11 studies were included. However, 3 studies were not included in the meta-analysis. Meta-analysis showed that mean weight increased (lean mass), ranging from 1.65 (95 % CI, 1.61–1.69) to 6.20 (95 % CI, 5.22–7.18) kg, although it was heterogeneous (I 2 = 98 %). Effect estimate was 3.59 [2.38–4.81]. Androgen therapy decreased fat mass; effect estimate was −1.78 [−2.57, −0.99] that analysis had also a high level of heterogeneity (I 2 = 81 %). The results suggest that testosterone replacement therapy is able to increase muscle mass in elderly men and that is affected by the time that the treatment is carried out and the method of administration of the drug.

Abstract: Curcumin is considered not only as a supplement of the diet but also as a drug in many types of diseases and even as a potential anti-aging compound. It can reduce inflammation that increases with age and accompanies almost all age-related diseases. It has been suggested that curcumin can play a beneficial role in the cardiovascular system. However, there are also data showing that curcumin can induce senescence in cancer cells, which is a beneficial effect in cancer therapy but an undesirable one in the case of normal cells. It is believed that cellular senescence accompanies age-related changes in the cardiovascular system. The aim of this study was to check if curcumin, in a certain range of concentrations, can induce senescence in cells building the vasculature. We have found that human vascular smooth muscle and endothelial cells derived from aorta are very sensitive to curcumin treatment and can senesce upon treatment with cytostatic doses. We observed characteristic senescence markers but the number of DNA damage foci decreased. Surprisingly, in vascular smooth muscle cell (VSMC) activation of DNA damage response pathway downstream of ataxia-telangiectasia mutated (ATM) was observed. ATM silencing and the supplementation of antioxidants, N-acetyl-L-cysteine (NAC) or trolox, did not reduce the number of senescent cells. Thus, we have shown that curcumin can induce senescence of cells building the vasculature, which is DNA damage and ATM independent and is not induced by increased reactive oxygen species (ROS) level. We postulate that an increase in the bioavailability of curcumin should be introduced very carefully considering senescence induction as a side effect.

Abstract: Participation in exercise programs is heartily recommended for older adults since the level of physical fitness directly influences functional independence. The aim of this present study was to investigate the effects of supervised Pilates exercise training on the physical function, hypothesizing that a period of Pilates exercise training (PET) can increase overall muscle strength, body composition, and balance, during single and dual-task conditions, in a group of post-menopausal women. Twenty-five subjects, aged 59 to 66 years old, were recruited. Eligible participants were assessed prior and after 3 months of PET performed twice per week. Muscular strength was evaluated with handgrip strength (HGS) test, 30-s chair sit-to-stand test (30CST), and abdominal strength (AST) test. Postural control and dual-task performance were measured through a stabilometric platform while dynamic balance with 8 ft up and go test. Finally, body composition was assessed by means of dual-energy X-ray absorptiometry. Statistically significant improvements were detected on HGS (+8.22%), 30CST (+23.41%), 8 ft up and go test (-5.95%), AST (+30.81%), medio-lateral oscillations in open eyes and dual-task condition (-22.03% and -10.37%). Pilates was effective in increasing upper body, lower body, and abdominal muscle strength. No changes on body composition were detected. Results on this investigation indicated also that 12-week of mat Pilates is not sufficient to determine a clinical meaningful improvement on static balance in single and dual-task conditions.

Abstract: We aimed to verify whether different levels of training performed regularly and voluntarily for many years could have an impact on one of the main issues of immunosenescence: the poor response to vaccines. We recruited 61 healthy elderly men (65-85 years old), 23 with a moderate training (MT) lifestyle (for 17.0 ± 3.2 years), 22 with an intense training (IT) lifestyle (for 25.9 ± 3.4 years), and 16 without a training lifestyle (NT). Fitness was evaluated through the IPAQ and VO2max consumption. The participants were evaluated regarding cognitive aspects, nutritional status, depression, and quality of life. Antibody titers were determined by hemagglutination inhibition assay prior to influenza vaccination and at 6 weeks and 6 months post-vaccination. Strains used were B, H3N2, and H1N1. Our groups were matched for most characteristics, except for those directly influenced by their lifestyles, such as BMI, VO2max, and MET. In general, MT and IT elderly men showed significantly higher antibody titers to the three vaccine strains post-vaccination than NT elderly men. There were also higher titers against B and H1N1 strains in the trained groups before vaccination. Additionally, there were higher proportions of seroprotected (titers ≥1:40) individuals in the pooled trained groups both at 6 weeks (B and H3N2, p < 0.05) and 6 months (H1N1, p < 0.05; B, p = 0.07). There were no significant differences between the MT and IT groups. Either a moderate or an intense training is associated with stronger and longstanding antibody responses to the influenza vaccine, resulting in higher percentages of seroprotected individuals.

Abstract: The amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of Alzheimer’s disease (AD) has provided robust neuropathological hallmarks of familial AD-like pattern at early ages, whereas senescence-accelerated mouse prone 8 (SAMP8) has a remarkable early senescence phenotype with pathological similarities to AD. The aim of this study was the investigation and characterization of cognitive and neuropathological AD markers in a novel mouse model that combines the characteristics of the APP/PS1 transgenic mouse model with a senescence-accelerated background of SAMP8 mice. Initially, significant differences were found regarding amyloid plaque formation and cognitive abnormalities. Bearing these facts in mind, we determined a general characterization of the main AD brain molecular markers, such as alterations in amyloid pathway, neuroinflammation, and hyperphosphorylation of tau in these mice along their lifetimes. Results from this analysis revealed that APP/PS1 in SAMP8 background mice showed alterations in the pathways studied in comparison with SAMP8 and APP/PS1, demonstrating that a senescence-accelerated background exacerbated the amyloid pathology and maintained the cognitive dysfunction present in APP/PS1 mice. Changes in tau pathology, including the activity of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3 β (GSK3β), differs, but not in a parallel manner, with amyloid disturbances.

Abstract: Training that focuses on strength, balance, and endurance, the so-called combined exercise, can enhance physical function, including gait, according to a literature review However, the effects of combined exercise on improving gait variability are limited The objective of this study is to investigate the effects of 12 weeks of combined exercise comprised of resistance, endurance, and balance training on gait performance in older adults Twenty-nine community-dwelling older adults were recruited and assigned to either the experimental group (n = 17) or the control group (n = 12) The 12-week intervention was a combined exercise program at 1 h per day and 3 days per week The participants received an assessment for both a 6-min walk and gait during both habitual walking and fast walking conditions at pre-intervention and after 8 and 12 weeks of exercise The 6-min walk was used to assess gait endurance GAITRite was used to evaluate gait An analysis of covariance with the pretest score as the covariate was used to determine the difference in each dependent variable between groups The level of significance was set as p less than 005 Our results showed significant between-group effects in the 6-min walk and velocity, stride time, and stride length in both conditions after 8 weeks of exercise and significant between-group effects in the 6-min walk test and all selected gait parameters in both conditions after 12 weeks of exercise Our findings demonstrate that a 12-week combined exercise program may positively affect gait endurance and gait performance including gait variability in habitual walking and fast walking conditions among older adults The current study provides important evidence of short-term combined exercise effects on improvements in gait performance

Abstract: Walking speed is a key vital sign in older people. Given the implications of slower gait speed, a large literature has identified health-related, behavioral, cognitive, and biological factors that moderate age-related decline in mobility. The present study aims to contribute to existing knowledge by examining whether subjective age, how old or young individuals experience themselves to be relative to their chronological age, contributes to walking speed. Participants were drawn from the 2008 and 2012 waves of the Health and Retirement Study (HRS, N = 2970) and the 2011 and 2013 waves of the National Health and Aging Trends Study (NHATS, N = 5423). In both the HRS and the NHATS, linear regression analysis revealed that a younger subjective age was associated with faster walking speed at baseline and with less decline over time, controlling for age, sex, education, and race. These associations were partly accounted for by depressive symptoms, disease burden, physical activity, cognition, body mass index, and smoking. Additional analysis revealed that feeling younger than one's age was associated with a reduced risk of walking slower than the frailty-related threshold of 0.6 m/s at follow-up in the HRS. The present study provides novel and consistent evidence across two large prospective studies for an association between the subjective experience of age and walking speed of older adults. Subjective age may help identify individuals at risk for mobility limitations in old age and may be a target for interventions designed to mitigate functional decline.

Abstract: Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments.

Abstract: Resveratrol is a polyphenol exhibiting antioxidant and neuroprotective effects in neurodegenerative diseases. However, neuroprotective properties during normal aging have not been clearly demonstrated. We analyzed the in vivo effects of chronic administration of resveratrol (20 mg/kg/day for 4 weeks) in old male rats (Wistar, 20 months), on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities which mediate central monoaminergic neurotransmitters synthesis, and besides, on hippocampal-dependent working memory test (radial maze). Our results show an age-related decline in neurochemical parameters that were reversed by resveratrol administration. The resveratrol treatment enhances serotonin (5-HT) levels in pineal gland, in hippocampus, and in striatum, and those of noradrenaline (NA) in hippocampus and also dopamine (DA) in striatum. These changes were largely due to an increased activity of TPH-1 (463 % in pineal gland), TPH-2 (70–51 % in hippocampus and striatum), and TH (150–36 % in hippocampus and striatum). Additionally, the observed hippocampal effects correlate with a resveratrol-induced restorative effect on working memory (radial maze). In conclusion, this study suggests resveratrol treatment as a restoring therapy for the impaired cognitive functions occurring along normal aging process, by preventing 5-HT, DA, and NA neurotransmission decline.

Abstract: Glucocorticoids are pleiotropic regulators of multiple cell types with critical roles in physiological systems that change across the life-course. Although glucocorticoids have been associated with aging, available data on the aging trajectory in basal circulating glucocorticoids are conflicting. A literature search reveals sparse life-course data. We evaluated (1) the profile of basal circulating corticosterone across the life-course from weaning (postnatal day—PND 21), young adult PND 110, adult PND 450, mature adult PND 650 to aged phase PND 850 in a well-characterized homogeneous rat colony to determine existence of significant changes in trajectory in the second half of life; (2) sex differences; and (3) whether developmental programming of offspring by exposure to maternal obesity during development alters the later-life circulating corticosterone trajectory. We identified (1) a fall in corticosterone between PND 450 and 650 in both males and females (p < 0.05) and (2) higher female than male concentrations (p < 0.05). (3) Using our five life-course time-point data set, corticosterone fell at a similar age but from higher levels in male and female offspring of obese mothers. In all four groups studied, there was a second half of life fall in corticosterone. Higher corticosterone levels in offspring of obese mothers may play a role in their shorter life-span, but the age-associated fall occurs at a similar time to control offspring. Although even more life-course time-points would be useful, a five life-course time-point analysis provides important new information on normative and programmed aging of circulating corticosterone.

Abstract: Aging is associated with a pro-inflammatory state, often referred to as inflammaging. The origin of the pro-inflammatory mediators and their role in the pathogenesis of the aging-associated diseases remain poorly understood. As aging is also associated with profound changes in the transcriptomic and epigenetic (e.g., DNA methylation) profiles of cells in the peripheral blood, we analyzed the correlation of these profiles with inflammaging using the "classical" marker interleukin-6 as an indicator. The analysis of the whole-genome peripheral blood mononuclear cell (PBMC) gene expression revealed 62 transcripts with expression levels that significantly correlated with the plasma interleukin-6 (IL-6) levels in men, whereas no correlations were observed in women. The Gene Ontology analysis of plasma IL-6-associated transcripts in men revealed processes that were linked to the inflammatory response. Additionally, an Ingenuity Pathway Analysis (IPA) pathway analysis identified Tec kinase signaling as an affected pathway and upstream regulator analysis predicted the activation of IL-10 transcript. DNA methylation was assessed using a HumanMethylation450 array. Seven genes with expression profiles that were associated with the plasma IL-6 levels in men were found to harbor CpG sites with methylation levels that were also associated with the IL-6 levels. Among these genes were IL1RN, CREB5, and FAIM3, which mapped to a network of inflammatory response genes. According to our results, inflammaging is manifested differently at the genomic level in nonagenarian men and women. Part of this difference seems to be of epigenetic origin. These differences point to the genomic regulation of inflammatory response and suggest that the gender-specific immune system dimorphism in older individuals could be accounted for, in part, by DNA methylation.

Abstract: The underlying factors related to the divergent findings of age-related fatigue for dynamic tasks are not well understood. The purpose here was to investigate age-related fatigability and recovery between a repeated constrained (isokinetic) and an unconstrained velocity (isotonic) task, in which participants performed fatiguing contractions at the velocity (isokinetic) or resistance (isotonic) corresponding with maximal power. To compare between tasks, isotonic torque–power relationships were constructed prior to and following both fatiguing tasks and during short-term recovery. Contractile properties were recorded from 9 old (~75 years) and 11 young (~25 years) men during three testing sessions. In the first session, maximal power was assessed, and sessions 2 and 3 involved an isokinetic or an isotonic concentric fatigue task performed until maximal power was reduced by 40 %. Compared with young, the older men performed the same number of contractions to task failure for the isokinetic task (~45 contractions), but 20 % fewer for the isotonic task (p < 0.05). Regardless of age and task, maximal voluntary isometric contraction strength, angular velocity, and power were reduced by ~30, ~13, and ~25 %, respectively, immediately following task failure, and only isometric torque was not recovered fully by 10 min. In conclusion, older men are more fatigable than the young when performing a repetitive maximal dynamic task at a relative resistance (isotonic) but not an absolute velocity (isokinetic), corresponding to maximal power.

Abstract: Exogenous treatment with the naturally occurring peptide relaxin increases arterial compliance and reduces vascular stiffness. In contrast, relaxin deficiency reduces the passive compliance of small renal arteries through geometric and compositional vascular remodeling. The role of endogenous relaxin on passive mechanical wall properties in other vascular beds is unknown. Importantly, no studies have investigated the effects of aging in arteries of relaxin-deficient mice. Therefore, we tested the hypothesis that mesenteric and femoral arteries stiffen with aging, and this is exacerbated with relaxin deficiency. Male wild-type (Rln (+/+)) and relaxin knockout (Rln (-/-)) mice were aged to 3, 6, 12, 18, and 23 months. Passive mechanical wall properties were assessed by pressure myography. In both genotypes, there was a significant increase in circumferential stiffening in mesenteric arteries with aging, whereas in the femoral artery, aging reduced volume compliance. This was associated with a reduced ability of the artery to lengthen with aging. The predominant phenotype observed in Rln (-/-) mice was reduced volume compliance in young mice in both mesenteric and femoral arteries. In summary, aging induces circumferential stiffening in mesenteric arteries and axial stiffening in femoral arteries. Passive mechanical wall properties of Rln (-/-) mouse arteries predominantly differ at younger ages compared with Rln (+/+) mice, suggesting that a lack of endogenous relaxin only has a minor effect on vascular aging.

Abstract: Cisplatin (CDDP) nephrotoxicity is one of the most common side effects in cancer treatment, causing the disruption of chemotherapy. In this study, we analyzed the influence of nongenetic factors on CDDP-induced nephrotoxiciy using the data from 182 CDDP-treated and 52 carboplatin (CBP)-treated patients. The mean change of eGFR (100% to baseline) in CDDP-treated patients was -9.2%, which was significantly lower than that in the population with CBP therapy. By using the chi-squared test and multivariate logistic regression analysis, age (≥50 years) is found associated with CDDP-induced nephrotoxicity, with odds ratio (OR) of 9.167 and 11.771, respectively. Three- and 18-month-old mice were employed to study the age-dependent susceptibility of CDDP-induced nephrotoxicity. Biochemical parameters, histopathogical examination, and mRNA biomarkers indicated that old mice were subjected to more severe kidney injury. In addition, old mice accumulated more CDDP in kidney than young mice, and the protein level of CDDP efflux transporter, MATE1, in aged mice kidney was 35% of that in young mice. Moreover, inflammatory receptor TLR4 was higher in the kidney of old mice, indicating the alteration of inflammatory signaling in old mice. After CDDP administration, the induced alterations of TNF-α, ICAM-1, and TLR4 were more extensive in old mice. To summarize, aging increased the susceptibility of CDDP-induced renal function decline or nephrotoxicity.

Abstract: It was reported in 1980s that ages at which peak performance was observed had remained remarkably stable in the past century, although absolute levels of athletic performance increased dramatically for the same time span. The emergence of older (masters) athletes in the past few decades has changed the demographics and age-spectrum of Olympic athletes. The primary aim of the present study was to determine whether the ages at which peak performance was observed had increased in the recent decades. The data spanning 114 years from the first Olympics (1898) to the most recent Olympics (2014) were collected using the publically available data. In the present study, ages at which Olympic medals (gold, silver, and bronze) were won were used as the indicators of peak performance age. Track and field, swimming, rowing, and ice skating events were analyzed. In men, peak performance age did not change significantly in most of the sporting events (except in 100 m sprint running). In contrast, peak performance ages in women have increased significantly since 1980s and consistently in all the athletic events examined. Interestingly, as women's peak performance age increased, they became similar to men's peak ages in many events. In the last 20-30 years, ages at which peak athletic performance is observed have increased in women but not in men.

Abstract: It has been suggested that leisure activity and physical exercise can be a protective factor for neuropsychological functions and are associated with a reduced risk of dementia. Thus, the purpose of this study was to investigate the influence of physical exercise and leisure on the neuropsychological functions of healthy older adults. The sample was composed of 51 sedentary female volunteers who were 60–70 years old and were distributed into three groups: A—control, B—leisure, and C—training. Volunteers were submitted to a physical and neuropsychological assessment at baseline and after 6 months. Groups A and B were monitored longitudinally three times a week. Group C improved their neuropsychological functioning and oxygen consumption compared to groups A and B (p = <0.05). The neuropsychological functions of groups A and B were significantly worse after 6 months of monitoring (p = <0.05). The data suggest that physical exercise improves neuropsychological functioning, although leisure activities may also improve this functioning. Thus, an aerobic physical fitness program can partially serve as a non-medication alternative for maintaining and improving these functions in older adults; however, leisure activities should also be considered.

Abstract: The adaptations of the human body resulting from the aging process especially loss of flexibility can increase the risk of falls and the risk of developing other health conditions. Exercise training, in particular the Pilates exercise method, has become an important form of physical activity that minimizes the deleterious effects of aging on flexibility. Few studies have evaluated the effect of this training method on body flexibility among elderly. We aimed to evaluate the effects of physical training using the Pilates method on body flexibility of elderly individuals. Eighteen elderly women and two elderly men (aged 70 ± 4 years) followed a 10-week Pilates training program. Individuals were recruited from the local community via open invitations. At study entry, none of them had limited mobility (walking requiring the use of walkers or canes). Furthermore, those with neurologic, muscular, or psychiatric disorders as well as those using an assistive device for ambulation were excluded secondary to limited participation. Flexibility assessment tests (flexion, extension, right and left tilt, and right and left rotation of the cervical and thoracolumbar spine; flexion, extension, abduction, and lateral and medial right and left rotation of the glenohumeral joint; flexion, extension, abduction, adduction, and lateral and medial rotation of the right and left hip; and flexion of the right and left knee) were performed by a blinded evaluator using a flexometer before and after the training period. All assessments were carried out at the same time of day. There was an observed increase in flexion (22.86%; p < 0.001), extension (10.49%; p < 0.036), and rotation to the left side (20.45%; p < 0.019) of the cervical spine; flexion (16.45%; p < 0.001), extension (23.74%; p = 0.006), lateral bending right (39.52%; p < 0.001) and left (38.02%; p < 0.001), and right rotation (24.85%; p < 0.001) and left (24.24%; p < 0.001) of the thoracolumbar spine; flexion (right--8.80%, p = 0.034; left--7.03%, p = 0.050), abduction (right--20.69%, p < 0.001; left--16.26%, p = 0.005), and external rotation (right--116.07% and left--143%; p < 0.001 for both directions) of the glenohumeral joint; flexion (right--15.83%, p = 0.050; left--9.55%, p = 0.047) of the hips; and bending (right--14.20%, p = 0.006; left--15.20%, p = 0.017) the knees. The joint with the greatest magnitude of improvement was the thoracolumbar spine. Thus, this type of training may minimize the deleterious effects of aging and may improve the functionality of elderly individuals, which would reduce the likelihood of accidents (especially falls).

Abstract: Ultraviolet (UV) exposure and menopause are known as the inducers of damage to the skin structure. The combination of these two factors accelerates the skin aging process. In this study, we aimed to evaluate the influence of UV and ovariectomy (OVX) on the permeation of drugs through the skin. The role of tight junctions (TJs) and adherens junctions (AJs) in the cutaneous absorption of extremely lipophilic permeants and macromolecules was explored. The OVX nude mouse underwent bilateral ovary removal. Both UVA and UVB were employed to irradiate the skin. The physiological and biochemical changes of the skin structure were examined with focus on transepidermal water loss (TEWL), skin color, immunohistochemistry, and mRNA levels of proteins. UVB and OVX increased TEWL, resulting in stratum corneum (SC) integrity disruption and dehydration. A hyperproliferative epidermis was produced by UVB. UVA caused a pale skin color tone due to keratinocyte apoptosis in the epidermis. E-cadherin and β-catenin showed a significant loss by both UVA and UVB. OVX downregulated the expression of filaggrin and involucrin. A further reduction was observed when UV and OVX were combined. The in vitro cutaneous absorption demonstrated that UV increased the skin permeation of tretinoin by about twofold. However, skin accumulation and flux of estradiol were not modified by photoaging. OVX basically revealed a negligible effect on altering the permeation of small permeants. OVX increased tretinoin uptake by the appendages from 1.36 to 3.52 μg/cm2. A synergistic effect on tretinoin follicular uptake enhancement was observed for combined UV and OVX. However, the intervention of OVX to photoaged skin resulted in less macromolecule (dextran, molecular weight = 4 kDa) accumulation in the skin reservoir because of retarded partitioning into dry skin. The in vivo percutaneous absorption of lipophilic dye examined by confocal microscopy had indicated that the SC was still important to controlling topical delivery, although the role of epidermal junctions could not be simply ignored.

Abstract: Declining physical function is a major health problem for older adults as it is associated with multiple comorbidities and mortality. Exercise has been shown to improve physical function, though response to exercise is variable. Conversely, drugs targeting the renin–angiotensin system (RAS) pathway, including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), are also reported to improve physical function. In the past decade, significant strides have been made to understand the complexity and specificity of the RAS system as it pertains to physical function in older adults. Prior findings have also determined that interactions between antihypertensive medications and exercise may influence physical function above and beyond either factor alone. We review the latest research on RAS, exercise, and physical function for older adults. We also outline future research aims in this area, including genetic influences and clinical phenotyping, for the purpose of maintaining or improving physical function through tailored treatments.