ResearchPad - Ageing https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The effect of age on cerebral blood flow responses during repeated and sustained stand to sit transitions]]> https://www.researchpad.co/product?articleinfo=N46a0a1ad-3e5c-4518-a1d1-64ffcaeedb87

Abstract

Introduction

Aging is associated with impaired cerebrovascular blood flow and function, attributed to reduced vasodilatory capacity of the cerebrovascular network. Older adults may also have an impaired relationship between changes in blood pressure and cerebral blood flow; however, previous reports conflict. This study aimed to compare the blood pressure and cerebral blood flow responses to both repeated and sustained stand‐to‐sit transitions in young and older adults, and to assess the relationship with cerebrovascular reactivity.

Methods

In 20 young (age: 24 ± 4 years) and 20 older (age: 71 ± 7 years) adults we compared middle cerebral artery flow velocity (MCAv), end‐tidal partial pressure of carbon dioxide (PETCO2), and blood pressure (mean arterial blood pressure [MAP]) during repeated stand‐to‐sit (10 s standing and 10 s sitting) and sustained stand‐to‐sit (3 min standing followed by 2 min sitting) transitions. Cerebrovascular reactivity to changes in carbon dioxide levels was assessed using a repeated breath‐hold test.

Results

The % change in MCAv per % change in MAP (%∆MCAv/%∆MAP) was higher in the older adults than in the young adults during repeated stand‐to‐sit transitions. During the sustained protocol the %∆MCAv/%∆MAP response was similar in both age groups. A high %∆MCAv/%∆MAP response during the repeated stand‐to‐sit protocol was associated with low cerebrovascular reactivity to CO2 (r = −.39; p < .01), which was significantly lower in the older adults.

Conclusion

These findings suggest that the higher %∆MCAv/%∆MAP during repeated stand–sit transitions was associated with impaired cerebrovascular reactivity. Impairments in endothelial function and vascular stiffness with age may contribute to the altered transient cerebral pressure–flow responses in older adults.

]]>
<![CDATA[Resting metabolic rate and skeletal muscle SERCA and Na+/K+ ATPase activities are not affected by fish oil supplementation in healthy older adults]]> https://www.researchpad.co/product?articleinfo=N44c6b39e-cb8b-4464-9413-be7b64084933

Abstract

Omega‐3 polyunsaturated fatty acids (PUFAs) have unique properties purported to influence several aspects of metabolism, including energy expenditure and protein function. Supplementing with n‐3 PUFAs may increase whole‐body resting metabolic rate (RMR), by enhancing Na+/K+ ATPase (NKA) activity and reducing the efficiency of sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) activity by inducing a Ca2+ leak‐pump cycle. The purpose of this study was to examine the effects of fish oil (FO) on RMR, substrate oxidation, and skeletal muscle SERCA and NKA pump function in healthy older individuals. Subjects (n = 16 females; n = 8 males; 65 ± 1 years) were randomly assigned into groups supplemented with either olive oil (OO) (5 g/day) or FO (5 g/day) containing 2 g/day eicosapentaenoic acid and 1 g/day docosahexaenoic acid for 12 weeks. Participants visited the laboratory for RMR and substrate oxidation measurements after an overnight fast at weeks 0 and 12. Skeletal muscle biopsies were taken during weeks 0 and 12 for analysis of NKA and SERCA function and protein content. There was a main effect of time with decrease in RMR (5%) and fat oxidation (18%) in both the supplementation groups. The kinetic parameters of SERCA and NKA maximal activity, as well as the expression of SR and NKA proteins, were not affected after OO and FO supplementation. In conclusion, these results suggest that FO supplementation is not effective in altering RMR, substrate oxidation, and skeletal muscle SERCA and NKA protein levels and activities, in healthy older men and women.

]]>
<![CDATA[A pilot study assessing reliability and age‐related differences in corticomuscular and intramuscular coherence in ankle dorsiflexors during walking]]> https://www.researchpad.co/product?articleinfo=N5b31d416-4d86-4c4f-aac7-f8a26bbd1d40

Abstract

Corticomuscular (CMC) and intramuscular (intraMC) coherence represent measures of corticospinal interaction. Both CMC and intraMC can be assessed during human locomotion tasks, for example, while walking. Corticospinal control of gait can deteriorate during the aging process and CMC and intraMC may represent an important monitoring means. However, it is unclear whether such assessments represent a reliable tool when performed during walking in an ecologically valid scenario and whether age‐related differences may occur. Wireless surface electroencephalography and electromyography were employed in a pilot study with young and old adults during overground walking in two separate sessions. CMC and intraMC analyses were performed in the gathered beta and lower gamma frequencies (i.e., 13–40 Hz). Significant log‐transformed coherence area was tested for intersessions test–retest reliability by determining intraclass correlation coefficient (ICC), yielding to low reliability in CMC in both younger and older adults. intraMC exclusively showed low reliability in the older adults, whereas intraMC in the younger adults revealed similar values as previously reported: test–retest reliability [ICC (95% CI): 0.44 (−0.23, 0.87); SEM: 0.46; MDC: 1.28; MDC%: 103; Hedge's g (95% CI): 0.54 (−0.13, 1.57)]. Significant differences between the age groups were observed in intraMC by either comparing the two groups with the first test [Hedge's g (95% CI): 1.55 (0.85, 2.15); p‐value: .006] or with the retest data [Hedge's g (95% CI): 2.24 (0.73, 3.70); p‐value: .005]. Notwithstanding the small sample size investigated, intraMC seems a moderately reliable assessment in younger adults. The further development and use of this measure in practical settings to infer corticospinal interaction in human locomotion in clinical practice is warranted and should help to refine the analysis. This necessitates involving larger sample sizes as well as including a wider number of lower limb muscles. Moreover, further research seems warranted by the observed differences in modulation mechanisms of corticospinal control of gait as ascertained by intraMC between the age groups.

]]>
<![CDATA[Role of sodium‐dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages]]> https://www.researchpad.co/product?articleinfo=N1b0c87a0-6340-43f5-84b9-f8529f1e5e90

Abstract

SLC34A3/NPT2c/NaPi‐2c/Npt2c is a growth‐related NaPi cotransporter that mediates the uptake of renal sodium‐dependent phosphate (Pi). Mutation of human NPT2c causes hereditary hypophosphatemic rickets with hypercalciuria. Mice with Npt2c knockout, however, exhibit normal Pi metabolism. To investigate the role of Npt2c in Pi homeostasis, we generated α‐klotho−/−/Npt2c−/− (KL2cDKO) mice and analyzed Pi homeostasis. α‐Klotho−/− (KLKO) mice exhibit hyperphosphatemia and markedly increased kidney Npt2c protein levels. Genetic disruption of Npt2c extended the lifespan of KLKO mice similar to that of α‐Klotho−/−/Npt2a−/− mice. Adult KL2cDKO mice had hyperphosphatemia, but analysis of Pi metabolism revealed significantly decreased intestinal and renal Pi (re)absorption compared with KLKO mice. The 1,25‐dihydroxy vitamin D3 concentration was not reduced in KL2cDKO mice compared with that in KLKO mice. The KL2cDKO mice had less severe soft tissue and vascular calcification compared with KLKO mice. Juvenile KL2cDKO mice had significantly reduced plasma Pi levels, but Pi metabolism was not changed. In Npt2cKO mice, plasma Pi levels began to decrease around the age of 15 days and significant hypophosphatemia developed within 21 days. The findings of the present study suggest that Npt2c contributes to regulating plasma Pi levels in the juvenile stage and affects Pi retention in the soft and vascular tissues in KLKO mice.

]]>
<![CDATA[Glucose‐induced oxidative stress and accelerated aging in endothelial cells are mediated by the depletion of mitochondrial SIRTs]]> https://www.researchpad.co/product?articleinfo=Na22d6eab-5378-421e-9004-747778d2064f

Abstract

Diabetic complications cause significant morbidity and mortality. Dysfunction of vascular endothelial cells (ECs), caused by oxidative stress, is a main mechanism of cellular damage. Oxidative stress accelerates EC senescence and DNA damage. In this study, we examined the role of mitochondrial sirtuins (SIRTs) in glucose‐induced oxidative stress, EC senescence, and their regulation by miRNAs. Human retinal microvascular endothelial cells (HRECs) were exposed to 5 mmol/L (normoglycemia; NG) or 25 mmol/L glucose (hyperglycemia; HG) with or without transfection of miRNA antagomirs (miRNA‐1, miRNA‐19b, and miRNA‐320; specific SIRT‐targeting miRNAs). Expressions of SIRT3, 4 and 5 and their targeting miRNAs were examined using qRT‐PCR and ELISAs were used to study SIRT proteins. Cellular senescence was investigated using senescence‐associated β‐gal stain; while, oxidative stress and mitochondrial alterations were examined using 8‐OHdG staining and cytochrome B expressions, respectively. A streptozotocin‐induced diabetic mouse model was also used and animal retinas and hearts were collected at 2 months of diabetes. In HRECs, HG downregulated the mRNAs of SIRTs, while SIRT‐targeting miRNAs were upregulated. ELISA analyses confirmed such downregulation of SIRTs at the protein level. HG additionally caused early senescence, endothelial‐to‐mesenchymal transition and oxidative DNA damage in ECs. These changes were prevented by the transfection of specific miRNA antagomirs and by resveratrol. Retinal and cardiac tissues from diabetic mice also showed similar reductions of mitochondrial SIRTs. Collectively, these findings demonstrate a novel mechanism in which mitochondrial SIRTs regulate glucose‐induced cellular aging through oxidative stress and how these SIRTs are regulated by specific miRNAs. Identifying such mechanisms may lead to the discovery of novel treatments for diabetic complications.

]]>
<![CDATA[Contusion spinal cord injury upregulates p53 protein expression in rat soleus muscle at multiple timepoints but not key senescence cytokines]]> https://www.researchpad.co/product?articleinfo=N67ed2511-161a-47e4-86e9-6d53074259af

Abstract

To determine whether muscle disuse after a spinal cord injury (SCI) produces elevated markers of cellular senescence and induces markers of the senescence‐associated secretory phenotypes (SASPs) in paralyzed skeletal muscle. Four‐month‐old male Sprague‐Dawley rats received a moderate‐severe (250 kiloDyne) T‐9 contusion SCI or Sham surgery and were monitored over 2 weeks, and 1‐, 2‐, or 3 months. Animals were sacrificed via isoflurane overdose and terminal exsanguination and the soleus was carefully excised and snap frozen. Protein expression of senescence markers p53, p27, and p16 was determined from whole soleus lysates using Western immunoblotting and RT‐qPCR was used to determine the soleus gene expression of IL‐1α, IL‐1β, IL‐6, CXCL1, and TNFα. SCI soleus muscle displayed 2‐ to 3‐fold higher total p53 protein expression at 2 weeks, and at 1 and 2 months when compared with Sham. p27 expression was stable across all groups and timepoints. p16 protein expression was lower at 3 months in SCI versus Sham, but not earlier timepoints. Gene expression was relatively stable between groups at 2 weeks. There were Surgery x Time interaction effects for IL‐6 and TNFα mRNA expression but not for IL‐1α, IL‐1β, or CXCL1. There were no main effects for time or surgery for IL‐1α, IL‐1β, or CXCL1, but targeted t tests showed reductions in IL‐1α and CXCL1 in SCI animals compared to Sham at 3 months and IL‐1β was reduced in SCI animals compared to Sham animals at the 2‐month timepoint. The elevation in p53 does not appear consistent with the induction of SASP because mRNA expression of cytokines associated with senescence was not uniformly upregulated and, in some instances, was downregulated in the early chronic phase of SCI.

]]>
<![CDATA[Effects of low and moderate treadmill exercise on liver of d ‐galactose‐exposed aging rat model]]> https://www.researchpad.co/product?articleinfo=N2be5e038-ffb2-46ec-8682-ae56c086c142

Abstract

Aging increases liver susceptibility to diseases and it causes inflammation in liver tissue which can lead to fibrosis. Studies suggest that aging is caused by the accumulation of free radicals. Lack of physical activity can lower hormone levels and increase free radicals that can accelerate the aging process. Hence, physical activity is very important to maintain functions of organs. This research was aimed to study the effects of low and moderate treadmill exercise on d‐Galactose‐exposed aging rat model by evaluating the degree of hepatic fibrosis, number of M1 and M2, and M1/M2 ratio. Twenty‐four 3‐month‐old male Wistar aging model rats were randomly divided into four groups, that is, three treatment groups with daily 300 mg kgBW−1 d‐Galactose injection administrated intraperitoneally for 4 weeks and 1 control group with normal saline injection. Two of the d‐Galactose treated groups were given low and moderate treadmill exercise for 4 weeks. It was concluded that low intensity treadmill exercise significantly lowered the degree of d‐Galactose‐exposed hepatic fibrosis, and moderate treadmill exercise was able to restore the injured liver tissue back to the non‐aging state. Administration of d‐Galactose causes inflammation marked by the elevated number of M1 and M2 macrophages. Moderate treadmill exercise drove M1/M2 ratio back to the control condition.

]]>
<![CDATA[The prospective relationship between social cohesion and depressive symptoms among older adults from Central and Eastern Europe]]> https://www.researchpad.co/product?articleinfo=5c82b2c7d5eed0c484e5a4c5

Background

Social cohesion has a potential protective effect against depression, but evidence for Central and Eastern Europe is lacking. We investigated the prospective association between social cohesion and elevated depressive symptoms in the Czech Republic, Russia and Poland, and assessed whether alcohol drinking and smoking mediated this association.

Methods

Cohort data from 15 438 older urban participants from the Health, Alcohol and Psychosocial factors In Eastern Europe project were analysed. Baseline social cohesion was measured by five questions, and depressive symptoms were measured 3 years later by the 10-item Center for Epidemiological Depression (CES-D) Scale. Nested logistic regression models estimated ORs of elevated depressive symptoms (CES-D 10 score ≥4) by z-scores and tertiles of social cohesion.

Results

Per 1 SD decrease in social cohesion score, adjusted ORs of elevated depressive symptoms were 1.13 (95% CI 1.05 to 1.23) and 1.05 (95% CI 0.99 to 1.13) in men and women, respectively. Further adjustment for smoking and drinking did not attenuate these associations in either men (OR=1.13, 95% CI 1.05 to 1.22) or women (OR=1.05, 95% CI 0.99 to 1.13). Similarly, the fully adjusted ORs comparing the lowest versus highest social cohesion tertile were 1.33 (95% CI 1.10 to 1.62) in men and 1.18 (95% CI 1.01 to 1.39) in women.

Conclusions

Lower levels of social cohesion was associated with heightened depressive symptoms after a 3-year follow-up among older Czech, Russian and Polish adults. These effects appeared stronger in men, and alcohol and smoking played no appreciable role in this association.

]]>
<![CDATA[Enhanced recovery after surgery—ERAS—principles, practice and feasibility in the elderly]]> https://www.researchpad.co/product?articleinfo=5b4c41bf463d7e06c7b529dc

This is a short overview of the principles of a novel development in surgery called enhanced recovery after surgery (ERAS) programs. This is an evidence-based approach to perioperative care that has shown to reduce complications and recovery time by 30–50%. The main mechanism is reduction of the stress reactions to the operation. These principles have been shown to be particularly well suited for the compromised patient and hence very good for the elderly people who often have co-morbidities and run a higher risk of complications.

]]>
<![CDATA[Intrahippocampal glucocorticoids generated by 11β-HSD1 affect memory in aged mice]]> https://www.researchpad.co/product?articleinfo=5b472116463d7e6b4f5a4589

11Beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) locally amplifies active glucocorticoids within specific tissues including in brain. In the hippocampus, 11β-HSD1 messenger RNA increases with aging. Here, we report significantly greater increases in intrahippocampal corticosterone (CORT) levels in aged wild-type (WT) mice during the acquisition and retrieval trials in a Y-maze than age-matched 11β-HSD1−/− mice, corresponding to impaired and intact spatial memory, respectively. Acute stress applied to young WT mice led to increases in intrahippocampal CORT levels similar to the effects of aging and impaired retrieval of spatial memory. 11β-HSD1−/− mice resisted the stress-induced memory impairment. Pharmacologic inhibition of 11β-HSD1 abolished increases in intrahippocampal CORT levels during the Y-maze trials and prevented spatial memory impairments in aged WT mice. These data provide the first in vivo evidence that dynamic increases in hippocampal 11β-HSD1 regenerated CORT levels during learning and retrieval play a key role in age- and stress-associated impairments of spatial memory.

]]>
<![CDATA[SIRT3 overexpression antagonizes high glucose accelerated cellular senescence in human diploid fibroblasts via the SIRT3–FOXO1 signaling pathway]]> https://www.researchpad.co/product?articleinfo=5ba02cff40307c5317cae7b6

Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin reported to be associated with human life span. Many recent studies have indicated that SIRT3 levels are elevated by exercise and caloric restriction, but whether SIRT3 influences cell senescence under stressed conditions in human diploid fibroblasts has not been established. Our data showed that expression of SIRT3 is elevated in human diploid fibroblasts under low glucose (3.3 mM glucose) growth conditions and decreased under high glucose (25 mM glucose) growth conditions. We have demonstrated that SIRT3 interacts with forkhead box protein O1 (FOXO1). High glucose levels also increased aging phenotypes and FOXO1 acetylation level. We have demonstrated that overexpression of SIRT3 under high glucose conditions reduces FOXO1 acetylation, suggesting that deacetylation of FOXO1 by SIRT3 elevates the expression of the FOXO1 target genes, catalase, and manganese superoxide dismutase (MnSOD) while decreasing senescence phenotypes. We studied the effects of SIRT3 protein knockdown by shRNA under low glucose conditions. The data showed that shRNA-SIRT3 accelerated senescence phenotypes and acetylation of FOXO1; the expression level of catalase and MnSOD decreased compared with the control group. As a consequence, SIRT3 antagonized cellular senescence with the characteristic features of delayed SA-β-gal staining, senescence-associated heterochromatin foci (SAHF) formation, and p16INK4A expression. These results demonstrate for the first time that SIRT3 overexpression antagonizes high glucose-induced cellular senescence in human diploid fibroblasts via the SIRT3–FOXO1 signaling pathway.

]]>
<![CDATA[Phospholipid composition and longevity: lessons from Ames dwarf mice]]> https://www.researchpad.co/product?articleinfo=5ba02d0340307c5317cae7b8

Membrane fatty acid (FA) composition is correlated with longevity in mammals. The “membrane pacemaker hypothesis of ageing” proposes that animals which cellular membranes contain high amounts of polyunsaturated FAs (PUFAs) have shorter life spans because their membranes are more susceptible to peroxidation and further oxidative damage. It remains to be shown, however, that long-lived phenotypes such as the Ames dwarf mouse have membranes containing fewer PUFAs and thus being less prone to peroxidation, as would be predicted from the membrane pacemaker hypothesis of ageing. Here, we show that across four different tissues, i.e., muscle, heart, liver and brain as well as in liver mitochondria, Ames dwarf mice possess membrane phospholipids containing between 30 and 60 % PUFAs (depending on the tissue), which is similar to PUFA contents of their normal-sized, short-lived siblings. However, we found that that Ames dwarf mice membrane phospholipids were significantly poorer in n-3 PUFAs. While lack of a difference in PUFA contents is contradicting the membrane pacemaker hypothesis, the lower n-3 PUFAs content in the long-lived mice provides some support for the membrane pacemaker hypothesis of ageing, as n-3 PUFAs comprise those FAs being blamed most for causing oxidative damage. By comparing tissue composition between 1-, 2- and 6-month-old mice in both phenotypes, we found that membranes differed both in quantity of PUFAs and in the prevalence of certain PUFAs. In sum, membrane composition in the Ames dwarf mouse supports the concept that tissue FA composition is related to longevity.

]]>
<![CDATA[Heritability of a skeletal biomarker of biological aging]]> https://www.researchpad.co/product?articleinfo=5b7d0c7e463d7e3157f9a0c9

Changes in the skeletal system, which include age-related bone and joint remodeling, can potentially be used as a biomarker of biological aging. The aim of the present study was to investigate the extent and mode of inheritance of skeletal biomarker of biological aging—osseographic score (OSS), in a large sample of ethnically homogeneous pedigrees. The investigated cohort comprised 359 Chuvashian families and included 787 men aged 18–89 years (mean 46.9) and 723 women aged 18–90 years (mean 48.5). The TOSS - transformed OSS standardized in 5-year age groups for each sex, was analyzed as a BA index. We evaluated familial correlations and performed segregation analysis. Results of our study suggest the familial aggregations of TOSS variation in the Chuvashian pedigrees. In a segregation analysis we found a significant major gene (MG) effect in the individual’s TOSS with a dominant most parsimonious model (H2 = 0.32). Genetic factors (MG genotypes) explained 47% of the residual OSS variance after age adjustment and after including sex-genotype interaction, they explained 52% of the residual variance. Results of our study also indicated that the inherited difference in the skeletal aging pattern in men lies mostly in the rate of aging, but in women in the age of the onset of the period of visible skeletal changes.

]]>
<![CDATA[Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high-fat diet]]> https://www.researchpad.co/product?articleinfo=5ae36273463d7e71c6fd9e45

Recent discoveries have revealed the key role of mTOR (target of rapamycin) in aging. Furthermore, rapamycin extends lifespan in mice, especially in female mice. Here, we treated obese male mice on high-fat diet with rapamycin given intermittently: either weekly (once a week) or alternating bi-weekly (three injections every other week). While only marginally reducing obesity, intermittent administration of rapamycin significantly extended lifespan. Significance was achieved for weekly treated group and for the three rapamycin-received groups combined. In weekly treatment group, 100% mice were alive by the age of 2 years, whereas 60% of mice died in untreated group by this age. The effect of weekly treatment on survival was highly significant and cannot be fully explained by partial reduction in obesity. Alternating bi-weekly treatments seem to be less effective than weekly treatment, although effects of additional factors (see Discussion) may not be excluded. After one year of treatment, all survived mice were sacrificed 8 days after the last administration of rapamycin to avoid its direct interference with parameters examined. Fasting levels of cardiac and hepatic p-S6, a marker of mTORC1 activity, were lower in weekly treatment group compared with control mice. In contrast, levels of p-Akt (S473), glucose, triglycerides and insulin were unchanged, whereas leptin and IGF-1 tended to be lower. Thus, weekly treatment with rapamycin may slow down aging in obese male mice on high-fat diet.

]]>
<![CDATA[Frailty and mortality are not influenced by mitochondrial DNA haplotypes in the very old]]> https://www.researchpad.co/product?articleinfo=5ad1cfca463d7e1bb7aa3cc3

Inherited genetic variation of mitochondrial DNA (mtDNA) could account for the missing heritability of human longevity and healthy aging. Here, we show no robust association between common genetic variants of mtDNA and frailty (an “unhealthy aging” phenotype) or mortality in 700, more than 85-year-old, participants of the Newcastle 85+ study. Conflicting data from different populations underscore our conclusion that there is currently no compelling link between inherited mtDNA variants and aging.

]]>
<![CDATA[Clearance of the mutant androgen receptor in motoneuronal models of spinal and bulbar muscular atrophy]]> https://www.researchpad.co/product?articleinfo=5ace7a0f463d7e1617a11974

Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease caused by an abnormal expansion of a tandem CAG repeat in exon 1 of the androgen receptor (AR) gene that results in an abnormally long polyglutamine tract (polyQ) in the AR protein. As a result, the mutant AR (ARpolyQ) misfolds, forming cytoplasmic and nuclear aggregates in the affected neurons. Neurotoxicity only appears to be associated with the formation of nuclear aggregates. Thus, improved ARpolyQ cytoplasmic clearance, which indirectly decreases ARpolyQ nuclear accumulation, has beneficial effects on affected motoneurons. In addition, increased ARpolyQ clearance contributes to maintenance of motoneuron proteostasis and viability, preventing the blockage of the proteasome and autophagy pathways that might play a role in the neuropathy in SBMA. The expression of heat shock protein B8 (HspB8), a member of the small heat shock protein family, is highly induced in surviving motoneurons of patients affected by motoneuron diseases, where it seems to participate in the stress response aimed at cell protection. We report here that HspB8 facilitates the autophagic removal of misfolded aggregating species of ARpolyQ. In addition, though HspB8 does not influence p62 and LC3 (two key autophagic molecules) expression, it does prevent p62 bodies formation, and restores the normal autophagic flux in these cells. Interestingly, trehalose, a well-known autophagy stimulator, induces HspB8 expression, suggesting that HspB8 might act as one of the molecular mediators of the proautophagic activity of trehalose. Collectively, these data support the hypothesis that treatments aimed at restoring a normal autophagic flux that result in the more efficient clearance of mutant ARpolyQ might produce beneficial effects in SBMA patients.

]]>
<![CDATA[Responsiveness of the innate immune system and glucose concentrations in the oldest old]]> https://www.researchpad.co/product?articleinfo=5acc2e19463d7e3ccf725670

Patients with diabetes mellitus show increased risk of infectious disease as well as disturbances in innate immunity. In critical care settings, hyperglycemia is associated with increased risk of sepsis. It is unclear whether elevated glucose concentrations and innate immunity are associated in a non-clinical setting. We aimed to assess the association between glucose concentrations and innate immune response in the oldest old, who are at increased risk of both disturbed glucose metabolism as well as infectious disease. This study was part of the Leiden 85-plus Study. In 562 subjects aged 85 years old of the general population, venous blood samples were taken for measurement of morning glucose, C-reactive protein (CRP) and glycated hemoglobin (HbA1c). The innate immune response was assessed by performing ex vivo whole blood lipopolysaccharide (LPS) stimulation for production capacity of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL1-β), interleukin 10 (IL-10) and interleukin 1 receptor antagonist (IL-1Ra). Using linear regression analysis, cross-sectional analysis between glucose and cytokine production capacity was performed. We found a significant negative association between glucose concentrations, but not HbA1c, and cytokine response capacity in four out of five measured cytokines (all p < 0.05). Both glucose and HbA1c were positively associated with circulating levels of CRP. Higher glucose concentrations in non-diabetic elderly are associated with lower innate immune response. As elderly show increased vulnerability for disturbances in glucose metabolism as well as infectious disease, this relation could be of clinical significance.

]]>
<![CDATA[Septic shock in older people: a prospective cohort study]]> https://www.researchpad.co/product?articleinfo=5989db03ab0ee8fa60bc782d

Background

Septic shock is the first cause of death in Intensive Care Units. Despite experimental data showing increased inflammatory response of aged animals following infection, the current accepted hypothesis claims that aged patients are immunocompromised, when compared to young individuals.

Results

Here, we describe a prospective cohort study designed to analyze the immune profile of this population.

Conclusion

Older people are as immunocompetent as the young individual, regarding the cytokines, chemokines and growth factors response to devastating infection.

]]>
<![CDATA[Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study]]> https://www.researchpad.co/product?articleinfo=5989d9f9ab0ee8fa60b71464

Background

Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored.

Results

Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD.

Conclusions

Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated.

]]>
<![CDATA[Immunological and nutritional factors in elderly people in low-level care and their association with mortality]]> https://www.researchpad.co/product?articleinfo=5989da5aab0ee8fa60b8fcba

Background

This study examines associations between markers of nutritional status and lymphocyte subsets and seeks to determine if lymphocyte profile is predictive of survival in elderly Australians residing in aged care facilities. Aged yet still ambulatory subjects (n = 88, 73% female) living in low-level care and requiring minimal assistance were studied for 143 weeks. At baseline when participants were aged (mean ± SD) 86.0 ± 5.9 years, dietary intake was determined by 3-day weighed food record, body composition was assessed by dual energy X-ray absorptiometry (DXA) and a venous blood sample was taken.

Results

At baseline assessment, study participants were consuming nutrient-poor diets and most had symptoms of chronic disease. Although overweight, 40% exhibited sarcopenia. Markers of nutritional status did not relate closely to immune cell numbers (absolute or relative), which on average were within the normal range. Men had lower numbers of CD3+CD4+ cells (CD4+ T cells), a higher proportion of CD3 CD16± CD56± (natural killer (NK) cells) and a higher ratio of NK: CD4+ T cells than women (all P < 0.05). The main age-related changes evident were decreased T cells, particularly low CD4+ T cell counts, and increased numbers of CD19+ (B-cell) and NK cells. During the 143 week duration of follow-up, about one quarter of the study participants died, with death more likely in men than women (P < 0.01). Poor survival was predicted by the presence of decreased numbers of CD4+ T cells (hazard ratio (HR) 0.919, P < 0.01) and expanded numbers of NK cells (HR 1.085, P < 0.05) in the blood, and therefore the presence of a high NK: CD4+ T cell ratio (HR 30.521, P < 0.01).

Conclusions

The NK: CD4+ T cell ratio may potentially have clinical utility for predicting longevity in elderly populations. Further studies are needed in other elderly populations to confirm this finding.

]]>