| 1. |
- Bengnér, Malin, et al.
(author)
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Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity.
- 2014
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In: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:2, s. 571-582
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Journal article (peer-reviewed)abstract
- Cytomegalovirus (CMV) infection induces profound changes in different subsets of the cellular immune system. We have previously identified an immune risk profile (IRP) where CMV-associated changes in the T cell compartment, defined as a CD4/CD8 ratio < 1, are associated with increased mortality in elderly people. Since natural killer (NK) cells have an important role in the defense against viral infections, we examined whether the expansion of CD8 + T cells seen in individuals with CD4/CD8 ratio < 1 is coupled to a parallel skewing of the NK cell compartment. A number of 151 subjects were examined with CMV serology and a flow cytometry panel for assessment of T cell and NK cell subsets. CMV-seropositive individuals had higher frequencies of CD57 + and NKG2C + NK cells and lower frequencies of NKG2A + NK cells, in line with a more differentiated NK cell compartment. Intriguingly, however, there was no correlation between CD4/CD8 ratio and NK cell repertoires among CMV-seropositive donors, despite the profound skewing of the T cell compartment in the group with CD4/CD8 ratio < 1. Conversely, donors with profound expansion of NK cells, defined as NKG2C + NK cells with high expression of CD57 and ILT-2, did not display more common changes in their T cell repertoire, suggesting that NK cell expansion is independent of the T cell-defined IRP. Altogether, these results indicate that the effect of CMV on CD8 T cells and NK cells is largely nonoverlapping and independent.
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| 2. |
- Crane, FL, et al.
(author)
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Plasma membrane redox and control of sirtuin
- 2005
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In: Age (Dordrecht, Netherlands). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 27:2, s. 147-152
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Journal article (peer-reviewed)
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| 6. |
- Hogenkamp, Pleunie S., et al.
(author)
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Late-life alcohol consumption and cognitive function in elderly men
- 2014
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In: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:1, s. 243-249
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Journal article (peer-reviewed)abstract
- Moderate alcohol consumption (one to two drinks per day) has been associated with better cognitive function and lower risk of developing dementia in the elderly. In light of alcohol's well-known neurotoxic properties, more evidence from well-controlled population-based studies is required. The objective of this study was to examine whether self-reported alcohol intake at age 70 is linked to cognitive function (assessed by trail making tests (TMTs) A and B, which are measures of attention, mental speed, and flexibility) in a population-based cohort consisting of 652 cognitively healthy elderly men. Linear regression models were used to assess both cross-sectional (i.e., age 70) and prospective (i.e., age 77) associations between alcohol intake and cognitive function. The analyses were adjusted for education, body mass index, energy intake, self-reported physical activity, smoking, a history of hypertension or diabetes, apolipoprotein E epsilon 4 status, and cholesterol levels at the age of 70. Baseline data were obtained from 1990 to 1996. Self-reported alcohol intake (mean 6.9 +/- 7.1 g/day) was associated with better performance on TMT-B at ages 70 and 77 (beta = -0.87, p < 0.001). In contrast, alcohol intake was not predictive of the difference in performance on these tests between ages 70 and 77. Despite cross-sectional associations with performance in a test of executive functioning, moderate intake of alcohol was not linked to differences in cognitive performance between ages 70 and 77 in the present study. Thus, our findings do not support the view that daily moderate alcohol consumption is a recommendable strategy to slow cognitive aging in elderly populations.
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| 14. |
- Strindhall, Jan, et al.
(author)
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The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals : the Swedish HEXA immune study
- 2013
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In: Age (Omaha). - : Springer Netherlands. - 0161-9152 .- 1574-4647. ; 35:3, s. 985-991
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Journal article (peer-reviewed)abstract
- The Swedish OCTO and NONA immune longitudinal studies were able to identify and confirm an immune risk profile (IRP) predictive of an increased 2-year mortality in very old individuals, 86–94 years of age. The IRP, was associated with persistent cytomegalovirus infection and characterized by inverted CD4/CD8 ratio and related to expansion of terminally differentiated effector memory T cells (TEMRA phenotype). In the present HEXA immune longitudinal study, we have examined a younger group of elderly individuals (n = 424, 66 years of age) in a population-based sample in the community of Jönköping, Sweden, to examine the relevance of findings previously demonstrated in the very old. Immunological monitoring that was conducted included T cell subsets and CMV-IgG and CMV-IgM serology. The result showed a prevalence of 15 % of individuals with an inverted CD4/CD8 ratio, which was associated with seropositivity to cytomegalovirus and increases in the level of TEMRA cells. The proportion of individuals with an inverted CD4/CD8 ratio was significantly higher in men whereas the numbers of CD3+CD4+ cells were significantly higher in women. In conclusion, these findings are very similar to those previously found by us in the Swedish longitudinal studies, suggesting that an immune profile previously identified in the very old also exists in the present sample of hexagenerians. Therefore, it will be important to examine clinical parameters, including morbidity and mortality, to assess whether the immune profile also is a risk profile associated with higher mortality in this sample of hexagenerians.
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| 15. |
- Stroikin, Yuri, et al.
(author)
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Lysosome-targeted stress reveals increased stability of lipofuscin-containing lysosomes
- 2008
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In: Age (Omaha). - : Springer. - 0161-9152 .- 1574-4647. ; 30:1, s. 31-42
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Journal article (peer-reviewed)abstract
- Cellular ageing is associated with accumulation of undegradable intralysosomal material, called lipofuscin. In order to accelerate the lipofuscin-accumulation, confluent, growth arrested human fibroblasts were cultured under hyperoxic conditions. To provide a better insight into the effects of lipofuscin on cellular functions, we compared lysosomal stability in control and lipofuscin-loaded human fibroblasts under conditions of lysosome-targeted stress induced by exposure to either the lysosomotropic detergent MSDH or the redox-cycling quinone naphthazarin. We show that lysosomal damage, assessed by acridine-orange relocation, translocation of cathepsin D to the cytosol, and alkalinization of lysosomes is more pronounced in control than in lipofuscin-loaded fibroblasts. Finding that lysosomal integrity was less affected or even preserved in case of lipofuscin-loaded cells enables us to suggest that lipofuscin exerts lysosome-stabilizing properties.
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| 17. |
- Titova, Olga E, et al.
(author)
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Dietary intake of eicosapentaenoic and docosahexaenoic acids is linked to gray matter volume and cognitive function in elderly
- 2013
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In: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 35:4, s. 1495-1505
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Journal article (peer-reviewed)abstract
- In the present study, we tested whether elderly with a high dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) would have higher cognitive test scores and greater brain volume than those with low dietary intake of these fatty acids. Data were obtained from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. The dietary intake of EPA and DHA was determined by a 7-day food protocol in 252 cognitively healthy elderly (122 females) at the age of 70 years. At age 75, participants' global cognitive function was examined, and their brain volumes were measured by magnetic resonance imaging (MRI). Three different multivariate linear regression models were applied to test our hypothesis: model A (adjusted for gender and age), model B (additionally controlled for lifestyle factors, e.g., education), and model C (further controlled for cardiometabolic factors, e.g., systolic blood pressure). We found that the self-reported 7-day dietary intake of EPA and DHA at the age of 70 years was positively associated with global gray matter volume (P < 0.05, except for model C) and increased global cognitive performance score (P < 0.05). However, no significant associations were observed between the dietary intake of EPA and DHA and global white matter, total brain volume, and regional gray matter, respectively. Further, no effects were observed when examining cognitively impaired (n = 27) elderly as separate analyses. These cross-sectional findings suggest that dietary intake of EPA and DHA may be linked to improved cognitive health in late life but must be confirmed in patient studies.
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| 18. |
- Tognon, Gianluca, 1976, et al.
(author)
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Does the Mediterranean diet predict longevity in the elderly? A Swedish perspective.
- 2011
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In: Age (Dordrecht, Netherlands). - : Springer Science and Business Media LLC. - 1574-4647 .- 0161-9152. ; 33:3, s. 439-50
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Journal article (peer-reviewed)abstract
- Dietary pattern analysis represents a useful improvement in the investigation of diet and health relationships. Particularly, the Mediterranean diet pattern has been associated with reduced mortality risk in several studies involving both younger and elderly population groups. In this research, relationships between dietary macronutrient composition, as well as the Mediterranean diet, and total mortality were assessed in 1,037 seventy-year-old subjects (540 females) information. Diet macronutrient composition was not associated with mortality, while a refined version of the modified Mediterranean diet index showed a significant inverse association (HR=0.93, 95% CI: 0.89; 0.98). As expected, inactive subjects, smokers and those with a higher waist circumference had a higher mortality, while a reduced risk characterized married and more educated people. Sensitivity analyses (which confirmed our results) consisted of: exclusion of one food group at a time in the Mediterranean diet index, exclusion of early deaths, censoring at fixed follow-up time, adjusting for activities of daily living and main cardiovascular risk factors including weight/waist circumference changes at follow up. In conclusion, we can reasonably state that a higher adherence to a Mediterranean diet pattern, especially by consuming wholegrain cereals, foods rich in polyunsaturated fatty acids, and a limited amount of alcohol, predicts increased longevity in the elderly.
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| 19. |
- Verdijk, Lex B., et al.
(author)
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Satellite cells in human skeletal muscle; from birth to old age
- 2014
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In: Age (Omaha). - Dordrecht : Springer Netherlands. - 0161-9152 .- 1574-4647. ; 36:2, s. 545-557
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Journal article (peer-reviewed)abstract
- Changes in satellite cell content play a key role in regulating skeletal muscle growth and atrophy. Yet, there is little information on changes in satellite cell content from birth to old age in humans. The present study defines muscle fiber type-specific satellite cell content in human skeletal muscle tissue over the entire lifespan. Muscle biopsies were collected in 165 subjects, from different muscles of children undergoing surgery (< 18 years; n = 13) and from the vastus lateralis muscle of young adult (18-49 years; n = 50), older (50-69 years; n = 53), and senescent subjects (70-86 years; n = 49). In a subgroup of 51 aged subjects (71 +/- 6 years), additional biopsies were collected after 12 weeks of supervised resistance-type exercise training. Immunohistochemistry was applied to assess skeletal muscle fiber type-specific composition, size, and satellite cell content. From birth to adulthood, muscle fiber size increased tremendously with no major changes in muscle fiber satellite cell content, and no differences between type I and II muscle fibers. In contrast to type I muscle fibers, type II muscle fiber size was substantially smaller with increasing age in adults (r = -0.56; P < 0.001). This was accompanied by an age-related reduction in type II muscle fiber satellite cell content (r = -0.57; P < 0.001). Twelve weeks of resistance-type exercise training significantly increased type II muscle fiber size and satellite cell content. We conclude that type II muscle fiber atrophy with aging is accompanied by a specific decline in type II muscle fiber satellite cell content. Resistance-type exercise training represents an effective strategy to increase satellite cell content and reverse type II muscle fiber atrophy.
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| 20. |
- Wåhlin-Larsson, Britta, 1959-, et al.
(author)
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The influence of systemic inflammation on skeletal muscle in physically active elderly women
- 2014
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In: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:5, s. 9718-
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Journal article (peer-reviewed)abstract
- The biological mechanisms responsible for the decline in skeletal muscle mass during aging remain unknown. It is hypothesized that elevations in the level of the acute phase C-reactive protein (CRP) negatively affect skeletal muscle mass in elderly. We examined the relationship between serum CRP and muscle mass in a population of active elderly women (65-70 years; n =23). Though all subjects were physically active, serum CRP levels were negatively associated to the amount of time spent in moderate-to-vigorous physical activity (R (2) = 0.20, P = 0.032) and to skeletal muscle mass (R (2) = 0.28, P = 0.009). We further aimed to determine the potential mechanisms behind the action of systemic inflammation on skeletal muscle by exposing myoblasts isolated from vastus lateralis to the different sera from each elderly woman. The doubling time (DT) of myoblasts increased when cells were exposed to sera with high CRP levels (R (2) = 0.27, P = 0.011), indicating that CRP contributes to the impairment of the proliferative rate of myoblasts in elderly. In order to further confirm our findings, we incubated human myoblasts in exogenous CRP. Exposition to exogenous CRP induced an increase in myoblast DT by 1.21-fold (P = 0.007) and a reduction in the expression of the proliferation marker ki-67 confirming the negative influence of CRP on myoblast proliferative rate. Collectively, these findings highlight the contribution of the systemic inflammatory status in the age-related decline in skeletal muscle function.
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| 21. |
- Zajitschek, Felix, et al.
(author)
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Interactive effects of sex, social environment, dietary restriction, and methionine on survival and reproduction in fruit flies
- 2013
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In: Age (Omaha). - : Springer. - 0161-9152 .- 1574-4647. ; 35:4, s. 1193-1204
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Journal article (peer-reviewed)abstract
- For the evolution of life histories, the trade-off between survival and reproduction is fundamental. Because sexes optimize fitness in different ways, this trade-off is expected to be resolved differently by males and females. Consequently, the sexes are predicted to respond differently to changes in resource availability. In fruit flies, research on dietary restriction has focused largely on females maintained in the absence of males, thereby neglecting sexual interactions that affect reproductive behavior of both sexes under more natural conditions. Here, we tested for the interactive effects of diet (40, 60, 100, and 300 % of standard yeast concentrations) and social environment (separate-sex vs. mixed-sex groups) on male and female Drosophila melanogaster life histories. Additionally, we evaluated the essential amino acid methionine as an agent that can uncouple the survival-reproduction trade-off. We show sex differences in the effect of social environment on survival patterns, but not on reproductive fitness. In females, yeast had a positive effect on reproduction and a negative effect on survival. In males, yeast had a negative effect on reproduction and the effect on survival depended on the social environment. Methionine reduced survival, but had no effect on reproduction. Our findings highlight the need to include both sexes and to vary social environments in research programs aimed at lifespan extension and call for further evaluation of the fecundity-restoring effect of methionine.
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