| 1. |
- Forsey, R.J., et al.
(författare)
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Plasma cytokine profiles in elderly humans
- 2003
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Ingår i: Mechanisms of Ageing and Development. - 0047-6374 .- 1872-6216. ; 124:4, s. 487-493
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- It is known that as we age, immune dysregulation often occurs, leading to failing health, and increased susceptibility to a number of different diseases. In this study we have investigated plasma cytokine profiles in order to identify immune markers of ageing. Plasma samples were obtained from 138 participants of the Swedish longitudinal NONA study (aged 86, 90 and 94 years) and 18 healthy Swedish volunteers (aged between 32 and 59 years). Our results show significantly increased levels of the pro-inflammatory cytokine interleukin-6 (P<0.0001) and soluble intercellular adhesion molecule-1 (P<0.0001) in the elderly group. The anti-inflammatory cytokine interleukin-10 did not alter with age whereas active (naturally processed) transforming growth factor-ß levels were significantly (P<0.0001) increased in the elderly group. No difference was observed between males and females. These data suggest that there are measurable changes in cytokine profiles with ageing with increased levels of potentially harmful molecules, which may contribute to immune alterations and declining health in the elderly population. © 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 2. |
- Nilsson, Bengt-Olof, et al.
(författare)
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Morbidity does not influence the T-cell immune risk phenotype in the elderly : Findings in the Swedish NONA Immune Study using sample selection protocols
- 2003
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Ingår i: Mechanisms of Ageing and Development. - : Elesvier. - 0047-6374 .- 1872-6216. ; 124:4, s. 469-476
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Tidskriftsartikel (refereegranskat)abstract
- A critical issue in our understanding of ageing and the immune system refers to the health status of the population from which inferences are drawn. The commonly used SENIEUR protocol, selecting individuals representing 'normal ageing' has recently been under debate because a substantial amount of individuals with various health problems are excluded. The aim of the present study was to investigate the influence of morbidity on immune parameters and to evaluate the associations with the T-cell immune risk phenotype (IRP), related to cytomegalovirus (CMV) seropositivity by applying the SENIEUR protocol and the OCTO-Immune protocol in the unselected population based sample (n = 138) of oldest-olds, participating in the Swedish NONA Immune Study. The SENIEUR protocol excluded over 90% of the sample whereas the OCTO-Immune protocol excluded almost 65% of the sample. Three independent groups, very healthy (SENIEUR), moderately healthy (OCTO-Immune) and frail (non-SENIEUR/non-OCTO-Immune) were created. Flow cytometry studies on lymphocyte sub-populations revealed no significant difference in CD4/CD8 ratio, CD3+CD4-CD8+, CD3+CD4+CD8-, CD8+CD57+CD28-, CD8+CD56+CD57- or CD8+CD56+CD57+ between the very healthy, moderately healthy and the frail subsamples. Our findings indicate that morbidity does not significantly influence the T-cell immune risk profile in the elderly, and we suggest the inclusion of broader samples in future immunogerontological studies.
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| 3. |
- Nilsson, Evalill, et al.
(författare)
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Preparation of artificial ceroid/lipofuscin by UV-oxidation of subcellular particles
- 1997
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier. - 0047-6374 .- 1872-6216. ; 99:1, s. 61-78
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have consistently shown that, during oxidative damage, glycation, and other oxygen stress-related reactions, various biomolecules are converted into ceroid- and lipofuscin-like fluorescent pigments. In this study, artificial ceroid/lipofuscin was produced by exposing rat liver fractions to UV-light overnight. Thiobarbituric acid reactive substances (TBARS) were formed in increasing amounts during the early stages of the process, but decreased as the material was later converted into a polymeric structure with few remaining peroxides. In the transmission electron microscope the artificial pigment showed lamellar structures and was osmiophilic. By energy-dispersive X-ray analysis the material was found to contain Ca and Fe in the same way as natural ceroid/lipofuscin. Moreover, it exhibited ceroid/lipofuscin-like, greenish-yellowish autofluorescence when assayed by microfluorometry, with a fluorescence maximum consistently found at 430 nm when excited at 350 nm. Identical fluorescence maxima were found for each fraction of rat liver that was used as the origin of the pigments, i.e. nuclei, mitochondria, lysosomes and microsomes. Extracts with either chloroform-methanol, or sodium dodecylsulphate, showed identical complex fluorescence. When the pigments were extracted by chloroform-methanol, five fluorescent bands were obtained after thin-layer chromatographic separation. Fibroblasts were found to endocytose the material, a process that converted them into lipofuscin-loaded cells of an aged phenotype as observed by light and electron microscopy. Similar fluorescence emission spectra were obtained from cells grown at 40% O2, in order to stimulate endogenous lipofuscin-formation, and from cells exposed to artificial ceroid/lipofuscin. The described technique for creating artificial ceroid/lipofuscin is relatively easy to perform and should provide a useful new tool to study the possible influences of ceroid/lipofuscin on lysosomal and cellular functions.
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| 4. |
- Aaseth, Jan, et al.
(författare)
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Coenzyme Q(10) supplementation - In ageing and disease
- 2021
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier Ireland Ltd. - 0047-6374 .- 1872-6216. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Coenzyme Q(10) (CoQ(10)) is an essential component of the mitochondrial electron transport chain. It is also an antioxidant in cellular membranes and lipoproteins. All cells produce CoQ(10) by a specialized cytoplasmatic-mitochondrial pathway. CoQ(10) deficiency can result from genetic failure or ageing. Some drugs including statins, widely used by inter alia elderly, may inhibit endogenous CoQ(10) synthesis. There are also chronic diseases with lower levels of CoQ(10) in tissues and organs. High doses of CoQ(10) may increase both circulating and intracellular levels, but there are conflicting results regarding bioavailability. Here, we review the current knowledge of CoQ(10) biosynthesis and primary and acquired CoQ(10) deficiency, and results from clinical trials based on CoQ(10) supplementation. There are indications that supplementation positively affects mitochondrial deficiency syndrome and some of the symptoms of ageing. Cardiovascular disease and inflammation appear to be alleviated by the antioxidant effect of CoQ(10). There is a need for further studies and well-designed clinical trials, with CoQ(10) in a formulation of proven bioavailability, involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ(10) treatment in neurodegenerative disorders, as well as in metabolic syndrome and its complications.
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| 5. |
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| 6. |
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| 7. |
- Caracciolo, Barbara, et al.
(författare)
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Cognitive decline, dietary factors and gut-brain interactions
- 2014
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 136, s. 59-69
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease. We reviewed the most recent findings in this rapidly expanding field. Some nutrients, such as vitamins and fatty acids, have been studied longer than others, but strong scientific evidence of an association is lacking even for these compounds. Specific dietary patterns, like the Mediterranean diet, may be more beneficial than a high consumption of single nutrients or specific food items. A strong link between vascular risk factors and dementia has been shown, and the association of diet with several vascular and metabolic diseases is well known. Other plausible mechanisms underlying the relationship between diet and cognitive decline, such as inflammation and oxidative stress, have been established. In addition to the traditional etiological pathways, new hypotheses, such as the role of the intestinal microbiome in cognitive function, have been suggested and warrant further investigation.
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| 8. |
- Chaillou, Thomas, 1985-, et al.
(författare)
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Glutamine-stimulated in vitro hypertrophy is preserved in muscle cells from older women
- 2020
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier. - 0047-6374 .- 1872-6216. ; 187
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Tidskriftsartikel (refereegranskat)abstract
- Age-related loss of muscle mass may result from reduced protein synthesis stimulation in response to anabolic stimuli, such as amino acid (AA) supplementation. The exact etiology of anabolic resistance to AA remains unclear. Therefore, the aim of this study was to investigate the anabolic response [cell size, protein synthesis and mechanistic target of rapamycin (mTOR) pathway] to the AA glutamine (a strong anabolic AA highly present in skeletal muscle) in myotubes obtained from 8 young (YW; 21-35 yrs) and 8 older (OW; 65-70 yrs) healthy women. This in vitro model of human primary myogenic cells explores the intrinsic behavior of muscle cells, while excluding potential influences of external factors. We showed that despite lower muscle mass, strength and cardiorespiratory fitness in OW compared to YW, myotube size (myotube diameter and area) and protein synthesis were not altered in OW, and glutamine-induced myotube hypertrophy and protein synthesis were preserved in OW. Apart from a lower glutamine-induced increase in P70S6 kinase phosphorylation in OW, no significant differences in other components of the mTOR pathway were observed between groups. Altogether, our data support the idea that the intrinsic capacity of muscle cells to respond to glutamine stimulation is preserved in healthy older women.
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| 9. |
- Davidy, Tal, et al.
(författare)
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A feasibility study of the combination of intranasal insulin with oral semaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design
- 2024
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Ingår i: Mechanisms of Ageing and Development. - 0047-6374 .- 1872-6216. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with semaglutide, a GLP-1 receptor agonist, to improve cognition in older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI). Since both INI and dulaglutide have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits. Methods: This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo, and intranasal placebo/oral placebo. Feasibility of combining INI with semaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with semaglutide (14 once daily), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization, white matter hyperintensities, Alzheimer's related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample. Discussion: This feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial (RCT) of the cognitive benefits of the combination of INI with semaglutide in individuals enriched for CVD and at high dementia risk.
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| 10. |
- de Magalhaes, J P, et al.
(författare)
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Cognitive aging as an extension of brain development : A model linking learning, brain plasticity, and neurodegeneration
- 2005
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 126:10, s. 1026-1033
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Forskningsöversikt (refereegranskat)abstract
- Differences in cognitive aging rates among mammals suggest that the pace of brain aging is genetically determined. In this work, we investigate the possibility that brain aging is an extension of brain development. It is possible that a subset of developmental mechanisms are extreme cases of antagonistic pleiotropy in that they are necessary for reaching adulthood and yet later cause age-related diseases. We derive a model linking development and brain aging in which childhood events essential for brain development later result in neurodegeneration. The hypothesis presented herein involves brain plasticity in which the same mechanisms that shape the adult phenotype continue at later ages contributing to cognitive dysfunction and eventually dementia. The same genetic program that decreases brain plasticity at early ages to focus our mind to the surrounding environment may continue in adulthood resulting in cognitive aging. Experimental implications for understanding neurodegeneration in this context are also discussed. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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