| 1. |
- Adelöf, Julia, 1990, et al.
(författare)
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Conclusions from a behavioral aging study on male and female F2 hybrid mice on age-related behavior, buoyancy in water-based tests, and an ethical method to assess lifespan.
- 2019
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:17, s. 7150-7168
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Tidskriftsartikel (refereegranskat)abstract
- Due to strain-specific behavioral idiosyncrasies, inbred mouse strains are suboptimal research models for behavioral aging studies. The aim of this study is to determine age-related behavioral changes of F2 hybrid C57BL/6NxBALB/c male and female mice. Lifespan was followed (nmales=48, nfemales=51) and cohorts of mature adult (7 months), middle-aged (15 months), and old mice (22 months of age; n=7-12 per group) were assessed regarding open-field activity, exploration, passive avoidance learning/memory, and depressive-like behavior. We found that both males and females demonstrated decreased exploratory behavior with age, while memory and depressive-like behavior were maintained. Females exhibited enhanced depressive-like behavior compared to males; however, a correlation between fat mass and swimming activity in the test directly accounted for 30-46% of this behavioral sex difference. In addition, we suggest a method to qualitatively estimate natural lifespan from survival analyses in which animals with signs of pain or severe disease are euthanized. This is, to our knowledge, the first behavioral study to consider both sex and aging in hybrid mice. We here define decreased exploratory behavior as a conserved hallmark of aging independent of sex, highlight the effect of buoyancy in water tests, and provide a method to assay lifespan with reduced animal suffering.
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| 2. |
- Andersson, Veronica, 1979, et al.
(författare)
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Enhancing protein disaggregation restores proteasome activity in aged cells
- 2013
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Ingår i: Aging-Us. - 1945-4589. ; 5:11, s. 802-812
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Tidskriftsartikel (refereegranskat)abstract
- The activity of the ubiquitin-proteasome system, UPS, declines during aging in several multicellular organisms. The reason behind this decline remains elusive. Here, using yeast as a model system, we show that while the level and potential capacity of the 26S proteasome is maintained in replicatively aged cells, the UPS is not functioning properly in vivo. As a consequence cytosolic UPS substrates, such as Delta ssCPY* are stabilized, accumulate, and form inclusions. By integrating a pGPD-HSP104 recombinant gene into the genome, we were able to constitutively elevate protein disaggregase activity, which diminished the accumulation of protein inclusions during aging. Remarkably, this elevated disaggregation restored degradation of a 26S proteasome substrate in aged cells without elevating proteasome levels, demonstrating that age-associated aggregation obstructs UPS function. The data supports the existence of a negative feedback loop that accelerates aging by exacerbating proteostatic decline once misfolded and aggregation-prone proteins reach a critical level.
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| 3. |
- Anisimov, Vladimir N., et al.
(författare)
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Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents
- 2011
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Ingår i: Aging. - 1945-4589. ; 3:11, s. 1110-1119
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. To this end, low pathogen (LP) or specific pathogen free (SPF) vivaria in St. Petersburg, Moscow, and Stockholm were used. For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions. It was found that substitution of a LP vivarium for a conventional (non-LP) one doubled the lifespan of female outbred mice, just as SkQ1 did in a non-LP vivarium. SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice in both LP and non-LP vivaria. In the SPF vivarium in Moscow, male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice housed individually in the SPF vivarium in Stockholm lived as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1. The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system. For males under LP or SPF conditions, SkQ1 increased the lifespan, affecting also some other system(s) responsible for aging.
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| 4. |
- Bachrach-Lindström, Margareta, et al.
(författare)
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Nutritional status and functional capacity after femoral neck fractures : a prospective randomized one-year follow-up study
- 2000
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Ingår i: Aging. - 1945-4589. ; 12:5, s. 366-374
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of this study was to evaluate the effect of two different surgical methods on nutritional status and functional capacity during the first postoperative year in patients with displaced femoral neck fractures. A further aim was to evaluate the effect of nutritional support. One hundred patients were randomly assigned to treatment with either primary total hip arthroplasty (THA) or osteosynthesis. Half of the patients in each treatment group received protein- and energy-enriched food in the hospital in addition to individual nutritional advice in order to optimize their intake of protein- and energy-rich food. Nutritional state and functional capacity were examined at baseline, one and three months, and one year after the operation. Pain was examined at three months and one year. The effect of nutritional intervention was equal within both surgical groups. Logistic regression showed that the dependent variable "living at one year" was significantly associated with serum albumin levels at one month. Advanced age, mental impairment and deteriorated nutritional status were predominant in the non-survivors. Overall, the primary THA group performed better compared with the osteosynthesis group concerning weight change over time, locomotion and pain. This study also showed that primary THA could safely be performed in the elderly without an increased postoperative mortality rate.
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| 7. |
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| 8. |
- Baracco, EE, et al.
(författare)
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α-Ketoglutarate inhibits autophagy
- 2019
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:11, s. 3418-3431
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Tidskriftsartikel (refereegranskat)
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| 9. |
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| 10. |
- Ben-Avraham, Dan, et al.
(författare)
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The complex genetics of gait speed : Genome-wide meta-analysis approach
- 2017
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 9:1, s. 209-246
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Cao, Zhi, et al.
(författare)
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Adherence to a healthy lifestyle counteracts the negative effects of risk factors on all-cause mortality in the oldest-old
- 2019
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:18, s. 7605-7619
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Tidskriftsartikel (refereegranskat)abstract
- In the study, we examined the extent to which the harmful effects of risk factors on all-cause mortality can be counteracted by healthy lifestyle practices in the oldest-old (80 years of age and older). A total of 17,660 oldest-old from China were followed up for up to 10 years. The data were analyzed using the Cox proportional hazard model with adjustment for potential confounders. We found that having a rural residence, not being married, having lower economic status, physical disability, impaired cognitive function, or comorbidity were all associated with an elevated risk of mortality. Using these factors, we computed a weighted risk score. Because never smoking, never drinking, doing physical exercise, having an ideal diet, and a normal weight were independently associated with lower mortality, we also combined them to compute a weighted protection score. Both scores were divided into lowest, middle, and highest groups using their tertiles. In joint effect analyses, participants with the combined highest-risk score and lowest-protection score profile had a nearly threefold higher joint death risk. These analyses show that adherence to a healthy lifestyle counteracts the negative effect of risk factors on all-cause mortality in the oldest-old by more than 20%.
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| 15. |
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| 17. |
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| 18. |
- Cedres, Nira, et al.
(författare)
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The interplay between gray matter and white matter neurodegeneration in subjective cognitive decline
- 2021
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 13:16, s. 19963-19977
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the interplay between gray matter (GM) and white matter (WM) neurodegeneration in subjective cognitive decline (SCD), including thickness across the whole cortical mantle, hippocampal volume, and integrity across the whole WM.Methods: We included 225 cognitively unimpaired individuals from a community-based cohort. Subjective cognitive complaints were assessed through 9 questions covering amnestic and non-amnestic cognitive domains. In our cohort, 123 individuals endorsed from one to six subjective cognitive complaints (i.e. they fulfilled the diagnostic criteria for SCD), while 102 individuals reported zero complaints. GM neurodegeneration was assessed through measures of cortical thickness across the whole mantle and hippocampal volume. WM neurodegeneration was assessed through measures of mean diffusivity (MD) across the whole WM skeleton. Mediation analysis and multiple linear regression were conducted to investigate the interplay between the measures of GM and WM neurodegeneration.Results: A higher number of complaints was associated with reduced hippocampal volume, cortical thinning in several frontal and temporal areas and the insula, and higher MD across the WM skeleton, with a tendency to spare the occipital lobe. SCD-related cortical thinning and increased MD were associated with each other and jointly contributed to complaints, but the contribution of cortical thinning to the number of complaints was stronger.Conclusions: Neurodegeneration processes affecting the GM and WM seem to be associated with each other in SCD and include brain areas other than those typically targeted by Alzheimer's disease. Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.
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| 19. |
- Chen, Chao, et al.
(författare)
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Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
- 2020
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 12:11, s. 10642-10662
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation-age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354PRODH, with effects significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18×10-7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354PRODH methylation and elderly age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20×10-6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.
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| 20. |
- Chen, Xin, 1980, et al.
(författare)
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UBB+1 reduces amyloid-beta cytotoxicity by activation of autophagy in yeast
- 2021
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 13:21, s. 23953-23980
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Tidskriftsartikel (refereegranskat)abstract
- UBB+1 is a mutated version of ubiquitin B peptide caused by a transcriptional frameshift due to the RNA polymerase II "slippage". The accumulation of UBB+1 has been linked to ubiquitin-proteasome system (UPS) dysfunction and neurodegeneration. Alzheimer's disease (AD) is defined as a progressive neurodegeneration and aggregation of amyloid-beta peptides (A beta) is a prominent neuropathological feature of AD. In our previous study, we found that yeast cells expressing UBB+1 at lower level display an increased resistance to cellular stresses under conditions of chronological aging. In order to examine the molecular mechanisms behind, here we performed genome-wide transcriptional analyses and molecular/cellular biology assays. We found that low UBB+1 expression activated the autophagy pathway, increased vacuolar activity, and promoted transport of autophagic marker ATG8p into vacuole. Furthermore, we introduced low UBB+1 expression to our humanized yeast AD models, that constitutively express A beta 42 and A beta 40 peptide, respectively. The co-expression of UBB+1 with A beta 42 or A beta 40 peptide led to reduced intracellular A beta levels, ameliorated viability, and increased chronological life span. In an autophagy deficient background strain (atg1 Delta), intracellular A beta levels were not affected by UBB+1 expression. Our findings offer insights for reducing intracellular A beta toxicity via autophagydependent cellular pathways under low level of UBB+1 expression.
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| 21. |
- Dantuma, NP, et al.
(författare)
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The price of longevity
- 2020
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 12:22, s. 22350-22351
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 22. |
- Deane, Colleen S., et al.
(författare)
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The acute transcriptional response to resistance exercise : impact of age and contraction mode
- 2019
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589. ; 11:7, s. 2111-2126
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Tidskriftsartikel (refereegranskat)abstract
- Optimization of resistance exercise (RE) remains a hotbed of research for muscle building and maintenance. However, the interactions between the contractile components of RE (i.e. concentric (CON) and eccentric (ECC)) and age, are poorly defined. We used transcriptomics to compare age-related molecular responses to acute CON and ECC exercise. Eight young (21 +/- 1 y) and eight older (70 +/- 1 y) exercise-naive male volunteers had vastus lateralis biopsies collected at baseline and 5 h post unilateral CON and contralateral ECC exercise. RNA was subjected to next-generation sequencing and differentially expressed (DE) genes tested for pathway enrichment using Gene Ontology (GO). The young transcriptional response to CON and ECC was highly similar and older adults displayed moderate contraction-specific profiles, with no GO enrichment. Age-specific responses to ECC revealed 104 DE genes unique to young, and 170 DE genes in older muscle, with no GO enrichment. Following CON, 15 DE genes were young muscle-specific, whereas older muscle uniquely expressed 147 up-regulated genes enriched for cell adhesion and blood vessel development, and 28 down-regulated genes involved in mitochondria! respiration, amino acid and lipid metabolism. Thus, older age is associated with contraction-specific regulation often without clear functional relevance, perhaps reflecting a degree of stochastic age-related dysregulation.
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| 23. |
- Dintica, Christina S., et al.
(författare)
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Joint trajectories of episodic memory and odor identification in older adults : patterns and predictors
- 2021
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 13:13, s. 17080-17096
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that olfactory function is closely linked to memory function. The aims of this study were to assess whether olfactory and episodic memory functions follow similar age-related decline trajectories, to identify different patterns of decline, as well as predictors of the patterns. 1023 participants from the Memory and Aging Project were followed for up to 8 years with annual episodic memory and odor identification assessments. Trajectories were modelled using growth mixture models. Multivariate logistic regression was used to identify pattern predictors. Three patterns of joint trajectories were identified; Class 1- stable average performance in both functions (n=690, 67.4%); Class 2- stable average episodic memory and declining odor identification (n=231, 22.6%); and Class 3- decline in both functions (n=102, 10.0%). Class predictors included age, sex, APOE epsilon 4 status, cognitive activity level and BMI. Participants in Class 3 were most likely to develop dementia. Episodic memory and olfactory function show similar trajectories in aging. Such classification can contribute to a better understanding of the factors related to cognitive decline and dementia.
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| 24. |
- Dintica, Christina S., et al.
(författare)
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The relation of poor mastication with cognition and dementia risk : a population-based longitudinal study
- 2020
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589. ; 12:9, s. 8536-8548
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the effect of poor masticatory ability on cognitive trajectories and dementia risk in older adults. 544 cognitively intact adults aged =50 were followed for up to 22 years. Cognitive domains (verbal, spatial/fluid, memory, and perceptual speed) were assessed at baseline and follow-ups. Dementia was ascertained according to standard criteria. Masticatory ability was assessed using the Eichner Index and categorized according to the number of posterior occlusal zones: A (all four), B (3-1), and C (none).At baseline, 147 (27.0%) participants were in Eichner category A, 169 (31.1%) in B and 228 (41.9%) in C. After the age of 65, participants in Eichner category B and C showed an accelerated decline in spatial/fluid abilities (beta: -0.16, 95% CI: -0.30 to -0.03) and (beta: -0.15, 95% CI: -0.28 to -0.02), respectively. Over the follow-up, 52 incident dementia cases were identified. Eichner categories B or C were not associated with an increased risk of dementia, compared to category A (Hazard Ratio [HR]: 0.83, 95% CI: 0.39 to 1.76 and HR: 0.63, 95% CI: 0.30 to 1.29, respectively).Poor masticatory ability is associated with an accelerated cognitive decline in fluid/spatial abilities, however it was not related to a higher risk of dementia.
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| 25. |
- Dong, Xuesi, et al.
(författare)
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Trans-omics biomarker model improves prognostic prediction accuracy for early-stage lung adenocarcinoma
- 2019
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:16, s. 6312-6335
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Tidskriftsartikel (refereegranskat)abstract
- Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase. Clinical and biomarker information was fused using an iCluster plus algorithm, which significantly distinguished patients into high- and low-mortality risk groups (Pdiscovery = 0.01 and Pvalidation = 2.71×10-3). Further, potential functional DNA methylation-gene expression-overall survival pathways were evaluated by causal mediation analysis. The effect of DNA methylation level on LUAD survival was significantly mediated through gene expression level. By adding DNA methylation and gene expression biomarkers to a model of only clinical data, the AUCs of the trans-omics model improved by 18.3% (to 87.2%) and 16.4% (to 85.3%) in discovery and validation phases, respectively. Further, concordance index of the nomogram was 0.81 and 0.77 in discovery and validation phases, respectively. Based on systematic review of published literatures, our model was superior to all existing models for early-stage LUAD. In summary, our trans-omics model may help physicians accurately identify patients with high mortality risk.
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