Browsing by Subject "Aging"

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  • Su, Jing; Ekman, Carl; Oskolkov, Nikolay; Lahti, Leo; Ström, Kristoffer; Brazma, Alvis; Groop, Leif; Rung, Johan; Hansson, Ola (2015)
    Background: Although high-throughput studies of gene expression have generated large amounts of data, most of which is freely available in public archives, the use of this valuable resource is limited by computational complications and non-homogenous annotation. To address these issues, we have performed a complete re-annotation of public microarray data from human skeletal muscle biopsies and constructed a muscle expression compendium consisting of nearly 3000 samples. The created muscle compendium is a publicly available resource including all curated annotation. Using this data set, we aimed to elucidate the molecular mechanism of muscle aging and to describe how physical exercise may alleviate negative physiological effects. Results: We find 957 genes to be significantly associated with aging (p <0.05, FDR = 5 %, n = 361). Aging was associated with perturbation of many central metabolic pathways like mitochondrial function including reduced expression of genes in the ATP synthase, NADH dehydrogenase, cytochrome C reductase and oxidase complexes, as well as in glucose and pyruvate processing. Among the genes with the strongest association with aging were H3 histone, family 3B (H3F3B, p = 3.4 x 10(-13)), AHNAK nucleoprotein, desmoyokin (AHNAK, p = 6.9 x 10(-12)), and histone deacetylase 4 (HDAC4, p = 4.0 x 10(-9)). We also discover genes previously not linked to muscle aging and metabolism, such as fasciculation and elongation protein zeta 2 (FEZ2, p = 2.8 x 10(-8)). Out of the 957 genes associated with aging, 21 (p <0.001, false discovery rate = 5 %, n = 116) were also associated with maximal oxygen consumption (VO2MAX). Strikingly, 20 out of those 21 genes are regulated in opposite direction when comparing increasing age with increasing VO2MAX. Conclusions: These results support that mitochondrial dysfunction is a major age-related factor and also highlight the beneficial effects of maintaining a high physical capacity for prevention of age-related sarcopenia.
  • Noreikiene, Kristina; Kuparinen, Anna; Merilae, Juha (2017)
    Telomeres are highly conserved nucleoprotein structures which protect genome integrity. The length of telomeres is influenced by both genetic and environmental factors, but relatively little is known about how different hereditary and environmental factors interact in determining telomere length. We manipulated growth rates and timing of maturation by exposing full-sib nine-spined sticklebacks (Pungitius pungitius) to two different temperature treatments and quantified the effects of temperature treatments, sex, timing of maturation, growth rate and family (genetic influences) on telomere length. We did not find the overall effect of temperature treatment on the relative telomere length. However, we found that variation in telomere length was related to timing of maturation in a sex- and temperature-dependent manner. Telomere length was negatively related to age at maturation in elevated temperature and early maturing males and females differed in telomere length. Variation in growth rate did not explain any variation in telomere length. The broad sense heritability (h(2)) of telomere length was estimated at h(2) = 0.31 - 0.47, suggesting predominance of environmental over genetic determinants of telomere length variability. This study provides the first evidence that age at maturation together with factors associated with it are influencing telomere length in an ectotherm. Future studies are encouraged to identify the extent to which these results can be replicated in other ectotherms.
  • Mikkola, Tuija M.; Kautiainen, Hannu; Mänty, Minna; von Bonsdorff, Mikaela B.; Kröger, Teppo; Eriksson, Johan G. (2021)
    Background Evidence on family caregivers' health is conflicting. Aim To investigate all-cause and cause-specific mortality in Finnish family caregivers providing high-intensity care and to assess whether age modifies the association between family caregiver status and mortality using data from multiple national registers. Methods The data include all individuals, who received family caregiver's allowance in Finland in 2012 (n = 42,256, mean age 67 years, 71% women) and a control population matched for age, sex, and municipality of residence (n = 83,618). Information on dates and causes of death between 2012 and 2017 were obtained from the Finnish Causes of Death Register. Results Family caregivers had lower all-cause mortality than the controls over the follow-up (8.1 vs. 11.6%) both among women (socioeconomic status adjusted hazard ratio [HR]: 0.64, 95% CI 0.61-0.68) and men (adjusted HR: 0.73, 95% CI 0.70-0.77). When modelling all-cause mortality as a function of age, younger caregivers had only slightly lower or equal mortality to their controls, but older caregivers had markedly lower mortality than their controls, up to more than 10% lower. Caregivers had a lower mortality rate for all the causes of death studied, namely cardiovascular, cancer, neurological, external, respiratory, gastrointestinal and dementia. The lowest risk was for dementia (subhazard ratio = 0.29, 95% CI 0.25-0.34). Conclusions Older family caregivers had lower mortality than the age-matched general population while mortality did not differ according to caregiver status in young adulthood. This age-dependent advantage in mortality is likely to reflect the selection of healthier individuals into the family caregiver role.
  • Tamminen, Henna; Kujala, Teija; Näätänen, Risto; Peltola, Maija S. (2021)
    Cognitive decline is evident in the elderly and it affects speech perception and foreign language learning. A listen-and-repeat training with a challenging speech sound contrast was earlier found to be effective in young monolingual adults and even in advanced L2 university students at the attentive and pre-attentive levels. This study investigates foreign language speech perception in the elderly with the same protocol used with the young adults. Training effects were measured with attentive behavioural measures (N = 9) and with electroencephalography measuring the pre-attentive mismatch negativity (MMN) response (N = 10). Training was effective in identification, but not in discrimination and there were no changes in the MMN. The most attention demanding perceptual functions which benefit from experience-based linguistic knowledge were facilitated through training, whereas pre-attentive processing was unaffected. The elderly would probably benefit from different training types compared to younger adults.
  • Tienari, Pentti; Myllykangas, Liisa (2017)
  • van der Lugt, Benthe; van Beek, Adriaan A.; Aalvink, Steven; Meijer, Ben; Sovran, Bruno; Vermeij, Wilbert P.; Brandt, Renata M. C.; de Vos, Willem M.; Savelkoul, Huub F. J.; Steegenga, Wilma T.; Belzer, Clara (2019)
    BackgroundThe use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1(-/7) mice with A. muciniphila for 10weeks and investigated histological, transcriptional and immunological aspects of intestinal health.ResultsThe thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80(+)CD273(-) B cells in Peyer's patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6C(int) monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila.ConclusionsAltogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.
  • van der Lugt, Benthe; van Beek, Adriaan A; Aalvink, Steven; Meijer, Ben; Sovran, Bruno; Vermeij, Wilbert P; Brandt, Renata M C; de Vos, Willem M; Savelkoul, Huub F J; Steegenga, Wilma T; Belzer, Clara (BioMed Central, 2019)
    Abstract Background The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1−/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. Results The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80+CD273− B cells in Peyer’s patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila. Conclusions Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.
  • Knight, Anna K.; Craig, Jeffrey M.; Theda, Christiane; Baekvad-Hansen, Marie; Bybjerg-Grauholm, Jonas; Hansen, Christine S.; Hollegaard, Mads V.; Hougaard, David M.; Mortensen, Preben B.; Weinsheimer, Shantel M.; Werge, Thomas M.; Brennan, Patricia A.; Cubells, Joseph F.; Newport, D. Jeffrey; Stowe, Zachary N.; Cheong, Jeanie L. Y.; Dalach, Philippa; Doyle, Lex W.; Loke, Yuk J.; Baccarelli, Andrea A.; Just, Allan C.; Wright, Robert O.; Tellez-Rojo, Mara M.; Svensson, Katherine; Trevisi, Letizia; Kennedy, Elizabeth M.; Binder, Elisabeth B.; Iurato, Stella; Räikkönen, Katri; Lahti, Jari M. T.; Pesonen, Anu-Katriina; Kajantie, Eero; Villa, Pia M.; Laivuori, Hannele; Hämäläinen, Esa; Park, Hea Jin; Bailey, Lynn B.; Parets, Sasha E.; Kilaru, Varun; Menon, Ramkumar; Horvath, Steve; Bush, Nicole R.; LeWinn, Kaja Z.; Tylavsky, Frances A.; Conneely, Karen N.; Smith, Alicia K. (2016)
    Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.
  • Girchenko, Polina; Lahti, Jari; Czamara, Darina; Knight, Anna K; Jones, Meaghan J; Suarez, Anna; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele; Villa, Pia M; Reynolds, Rebecca M; Kobor, Michael S; Smith, Alicia K; Binder, Elisabeth B; Räikkönen, Katri (BioMed Central, 2017)
    Abstract Background A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage. Results DNAm GA acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at birth was associated with maternal age of over 40 years at delivery, pre-eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and treatment with antenatal betamethasone in the index pregnancy, lower neonatal birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD; i.e., younger DNAm GA than chronological GA) of the offspring at birth was associated with insulin-treated gestational diabetes mellitus (GDM) in a previous pregnancy and Sjögren’s syndrome. These findings were more accentuated when the DNAm GA calculation was based on the raw difference between DNAm GA and GA than on the residual from the linear regression of DNAm GA on GA. Conclusions Our findings show that variations in the DNAm GA of the offspring at birth are associated with a number of maternal and offspring characteristics known to reflect exposure to prenatal environmental adversity. Future studies should be aimed at determining if this biological variation is predictive of developmental adversity.
  • Girchenko, Polina; Lahti, Jari; Czamara, Darina; Knight, Anna K.; Jones, Meaghan J.; Suarez Figueiredo, Anna; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele; Villa, Pia M.; Reynolds, Rebecca M.; Kobor, Michael S.; Smith, Alicia K.; Binder, Elisabeth B.; Räikkönen, Katri (2017)
    Background: A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage. Results: DNAm GA acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at birth was associated with maternal age of over 40 years at delivery, pre-eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and treatment with antenatal betamethasone in the index pregnancy, lower neonatal birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD; i.e., younger DNAm GA than chronological GA) of the offspring at birth was associated with insulin-treated gestational diabetes mellitus (GDM) in a previous pregnancy and Sjogren's syndrome. These findings were more accentuated when the DNAm GA calculation was based on the raw difference between DNAm GA and GA than on the residual from the linear regression of DNAm GA on GA. Conclusions: Our findings show that variations in the DNAm GA of the offspring at birth are associated with a number of maternal and offspring characteristics known to reflect exposure to prenatal environmental adversity. Future studies should be aimed at determining if this biological variation is predictive of developmental adversity.
  • Stephen, Ruth; Liu, Yawu; Ngandu, Tiia; Rinne, Juha O.; Kemppainen, Nina; Parkkola, Riitta; Laatikainen, Tiina; Paajanen, Teemu; Hanninen, Tuomo; Strandberg, Timo; Antikainen, Riitta; Tuomilehto, Jaakko; Keinanen Kiukaanniemi, Sirkka; Vanninen, Ritva; Helisalmi, Seppo; Levalahti, Esko; Kivipelto, Miia; Soininen, Hilkka; Solomon, Alina (2017)
    Background: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile. Objectives: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures. Methods: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation. Results: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (beta- coefficient -0.29, p = 0.001) and hippocampal volume (beta- coefficient -0.28, p = 0.003), lower cortical thickness (beta-coefficient -0.19, p = 0.042), and poorer cognition (beta-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p <0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15,95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation. Conclusions: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.
  • Oja, S.; Komulainen, P.; Penttilä, A.; Nystedt, J.; Korhonen, M. (BioMed Central, 2018)
    Abstract Background Senescent cells are undesirable in cell therapy products due to reduced therapeutic activity and risk of aberrant cellular effects, and methods for assessing senescence are needed. Early-passage mesenchymal stromal cells (MSCs) are known to be small and spindle-shaped but become enlarged upon cell aging. Indeed, cell morphology is routinely evaluated during MSC production using subjective methods. We have therefore explored the possibility of utilizing automated imaging-based analysis of cell morphology in clinical cell manufacturing. Methods An imaging system was adopted for analyzing changes in cell morphology of bone marrow-derived MSCs during long-term culture. Cells taken from the cultures at the desired passages were plated at low density for imaging, representing morphological changes observed in the clinical-grade cultures. The manifestations of aging and onset of senescence were monitored by population doubling numbers, expression of p16INK4a and p21Cip1/Waf1, β-galactosidase activity, and telomeric terminal restriction fragment analysis. Results Cell area was the most statistically significant and practical parameter for describing morphological changes, correlating with biochemical senescence markers. MSCs from passages 1 (p1) and 3 (p3) were remarkably uniform in size, with cell areas between 1800 and 2500 μm2. At p5 the cells began to enlarge resulting in a 4.8-fold increase at p6–9 as compared to p1. The expression of p16INK4a and activity of β-galactosidase had a strong correlation with the increase in cell area, whereas the expression of p21Cip1/Waf1 reached its maximum at the onset of growth arrest and subsequently decreased. Mean telomere length shortened at an apparently constant rate during culture, from 8.2 ± 0.3 kbp at p1, reaching 6.08 ± 0.6 kbp at senescence. Conclusions Imaging analysis of cell morphology is a useful tool for evaluating aging in cell cultures throughout the lifespan of MSCs. Our findings suggest that imaging analysis can reproducibly detect aging-related changes in cell morphology in MSC cultures. These findings suggest that cell morphology is still a supreme measure of cell quality and may be utilized to develop new noninvasive imaging-based methods to screen and quantitate aging in clinical-grade cell cultures.
  • Oja, S.; Komulainen, P.; Penttilä, A.; Nystedt, J.; Korhonen, M. (2018)
    Background: Senescent cells are undesirable in cell therapy products due to reduced therapeutic activity and risk of aberrant cellular effects, and methods for assessing senescence are needed. Early-passage mesenchymal stromal cells (MSCs) are known to be small and spindle-shaped but become enlarged upon cell aging. Indeed, cell morphology is routinely evaluated during MSC production using subjective methods. We have therefore explored the possibility of utilizing automated imaging-based analysis of cell morphology in clinical cell manufacturing. Methods: An imaging system was adopted for analyzing changes in cell morphology of bone marrow-derived MSCs during long-term culture. Cells taken from the cultures at the desired passages were plated at low density for imaging, representing morphological changes observed in the clinical-grade cultures. The manifestations of aging and onset of senescence were monitored by population doubling numbers, expression of p16(INK4)a and p21(Cip1/Waf1), beta-galactosidase activity, and telomeric terminal restriction fragment analysis. Results: Cell area was the most statistically significant and practical parameter for describing morphological changes, correlating with biochemical senescence markers. MSCs from passages 1 (p1) and 3 (p3) were remarkably uniform in size, with cell areas between 1800 and 2500 mu m(2). At p5 the cells began to enlarge resulting in a 4.8-fold increase at p6-9 as compared to p1. The expression of p16(INK4a) and activity of beta-galactosidase had a strong correlation with the increase in cell area, whereas the expression of p21(Cip1/Waf1) reached its maximum at the onset of growth arrest and subsequently decreased. Mean telomere length shortened at an apparently constant rate during culture, from 8.2 +/- 0.3 kbp at p1, reaching 6.08 +/- 0.6 kbp at senescence. Conclusions: Imaging analysis of cell morphology is a useful tool for evaluating aging in cell cultures throughout the lifespan of MSCs. Our findings suggest that imaging analysis can reproducibly detect aging-related changes in cell morphology in MSC cultures. These findings suggest that cell morphology is still a supreme measure of cell quality and may be utilized to develop new noninvasive imaging-based methods to screen and quantitate aging in clinical-grade cell cultures.
  • Mikkola, Tuija M.; Kautiainen, Hannu; von Bonsdorff, Mikaela B.; Salonen, Minna K.; Wasenius, Niko; Kajantie, Eero; Eriksson, Johan G. (2020)
    Purpose Most studies examining the associations between body composition and health-related quality of life (HRQoL) in older age have been cross-sectional and analyzed only fat or lean mass. Hence, it is poorly known whether fat and lean mass are independently associated with subsequent changes in HRQoL. We investigated whether baseline lean and fat mass are associated with changes in HRQoL over a 10-year period in older adults. Methods We studied 1044 men and women from the Helsinki Birth Cohort Study (age 57-70 years at baseline). Bioelectrical impedance analysis was used to derive baseline fat mass index (FMI, fat mass/height(2)) and lean mass index (lean mass/height(2)), dichotomized at sex-specific medians. HRQoL was assessed using RAND 36-item Health Survey at baseline and follow-up 10 years later. Results When controlled for lean mass and adjusted for potential confounders, high baseline FMI was associated with a greater decline in general health (standardized regression coefficient [beta] = - 0.13, p = 0.001), physical functioning (beta = - 0.11, p = 0.002), role physical (beta = - 0.13, p = 0.003), vitality (beta = - 0.08, p = 0.027), role emotional (beta = - 0.12, p = 0.007), and physical component score (beta = - 0.14, p <0.001). High baseline FMI was also associated with low HRQoL in all physical domains at baseline (beta: from - 0.38 to - 0.10). Lean mass was not strongly associated with HRQoL at baseline or change in HRQoL. Conclusion In older community-dwelling adults, higher fat mass is, independent of lean mass, associated with lower physical HRQoL and greater decline in HRQoL. Prevention of adiposity may contribute to preservation of a good quality of life in older age.
  • Kaivola, Karri; Salmi, Samuli J; Jansson, Lilja; Launes, Jyrki; Hokkanen, Laura; Niemi, Anna-Kaisa; Majamaa, Kari; Lahti, Jari; Eriksson, Johan G; Strandberg, Timo; Laaksovirta, Hannu; Tienari, Pentti J (BioMed Central, 2020)
    Abstract The hexanucleotide repeat expansion in intron 1 of the C9orf72 gene causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In addition to the effects of the pathogenic expansion, a role of intermediate-length alleles has been suggested in ALS, corticobasal degeneration and Parkinson’s disease. Due to the rarity of intermediate-length alleles with over 20 repeats and the geographical variability in their frequency, large studies that account for population stratification are needed to elucidate their effects. To this aim, we used repeat-primed PCR and confirmatory PCR assays to determine the C9orf72 repeat allele lengths in 705 ALS patients and 3958 controls from Finland. After exclusion of expansion carriers (25.5% of the ALS patients and 0.2% of the controls), we compared the frequency of intermediate-length allele carriers of 525 ALS cases and 3950 controls using several intermediate-length allele thresholds (7–45, 17–45, 21–45, 24–45 and 24–30). The carriership of an intermediate-length allele did not associate with ALS (Fisher’s test, all p ≥ 0.15) nor was there any association with survival (p ≥ 0.33), when we divided our control group into three age groups (18–65, 66–84 and 85–105 years). Carriership of two intermediate-length alleles was associated with ALS, when the longer allele was ≥ 17 repeats (p = 0.002, OR 5.32 95% CI 2.02–14.05) or ≥ 21 repeats (p = 0.00016, OR 15.21 95% CI 3.79–61.0). Our results show that intermediate-length alleles are a risk factor of ALS when present in both alleles, whereas carrying just one intermediate-length allele was not associated with ALS or survival.
  • Kaivola, Karri; Salmi, Samuli J.; Jansson, Lilja; Launes, Jyrki; Hokkanen, Laura; Niemi, Anna-Kaisa; Majamaa, Kari; Lahti, Jari; Eriksson, Johan G.; Strandberg, Timo; Laaksovirta, Hannu; Tienari, Pentti J. (2020)
    The hexanucleotide repeat expansion in intron 1 of the C9orf72 gene causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In addition to the effects of the pathogenic expansion, a role of intermediate-length alleles has been suggested in ALS, corticobasal degeneration and Parkinson's disease. Due to the rarity of intermediate-length alleles with over 20 repeats and the geographical variability in their frequency, large studies that account for population stratification are needed to elucidate their effects. To this aim, we used repeat-primed PCR and confirmatory PCR assays to determine the C9orf72 repeat allele lengths in 705 ALS patients and 3958 controls from Finland. After exclusion of expansion carriers (25.5% of the ALS patients and 0.2% of the controls), we compared the frequency of intermediate-length allele carriers of 525 ALS cases and 3950 controls using several intermediate-length allele thresholds (7-45, 17-45, 21-45, 24-45 and 24-30). The carriership of an intermediate-length allele did not associate with ALS (Fisher's test, all p >= 0.15) nor was there any association with survival (p >= 0.33), when we divided our control group into three age groups (18-65, 66-84 and 85-105 years). Carriership of two intermediate-length alleles was associated with ALS, when the longer allele was >= 17 repeats (p=0.002, OR 5.32 95% CI 2.02-14.05) or >= 21 repeats (p=0.00016, OR 15.21 95% CI 3.79-61.0). Our results show that intermediate-length alleles are a risk factor of ALS when present in both alleles, whereas carrying just one intermediate-length allele was not associated with ALS or survival.
  • Stenholm, Sari; Solovieva, Svetlana; Viikari-Juntura, Eira; Aalto, Ville; Kivimaki, Mika; Vahtera, Jussi (2017)
    Background: Retirement is a major life transition affecting health behaviors. The aim of this study was to examine within-individual changes in body mass index (BMI) during transition from full-time work to statutory retirement by sex and physical work characteristics. Methods: A multiwave cohort study repeated every 4 years and data linkage to records from retirement registers. Participants were 5426 Finnish public-sector employees who retired on a statutory basis in 2000-2011 and who reported their body weight one to three times prior to (w(-3), w(-2), w(-1)), and one to three times after (w(+1), w(+2), w(+3)) retirement. Results: During the 4-year retirement transition (w(+1), vs. w(-1)) men showed decline in BMI, which was most marked among men with sedentary work (-0.18 kg/m(2), 95% CI -.30 to -0.05). In contrast, BMI increased during retirement transition in women and was most marked among women with diverse (0.14 kg/m(2), 95% CI 0.08 to 0.20) or physically heavy work (0.31 kg/m(2), 95% CI 0.16 to 0.45). Physical activity during leisure time or commuting to work, alcohol consumption or smoking did not explain the observed changes during retirement transition. Conclusions: In this study statutory retirement was associated with small changes in BMI. Weight loss was most visible in men retiring from sedentary jobs and weight gain in women retiring from diverse and physically heavy jobs.
  • Stenholm, Sari; Solovieva, Svetlana; Viikari-Juntura, Eira; Aalto, Ville; Kivimäki, Mika; Vahtera, Jussi (BioMed Central, 2017)
    Abstract Background Retirement is a major life transition affecting health behaviors. The aim of this study was to examine within-individual changes in body mass index (BMI) during transition from full-time work to statutory retirement by sex and physical work characteristics. Methods A multiwave cohort study repeated every 4 years and data linkage to records from retirement registers. Participants were 5426 Finnish public-sector employees who retired on a statutory basis in 2000–2011 and who reported their body weight one to three times prior to (w−3, w−2, w−1), and one to three times after (w+1, w+2, w+3) retirement. Results During the 4-year retirement transition (w+1, vs. w−1) men showed decline in BMI, which was most marked among men with sedentary work (−0.18 kg/m2, 95% CI −.30 to −0.05). In contrast, BMI increased during retirement transition in women and was most marked among women with diverse (0.14 kg/m2, 95% CI 0.08 to 0.20) or physically heavy work (0.31 kg/m2, 95% CI 0.16 to 0.45). Physical activity during leisure time or commuting to work, alcohol consumption or smoking did not explain the observed changes during retirement transition. Conclusions In this study statutory retirement was associated with small changes in BMI. Weight loss was most visible in men retiring from sedentary jobs and weight gain in women retiring from diverse and physically heavy jobs.
  • Stenholm, Sari; Pulakka, Anna; Kawachi, Ichiro; Oksanen, Tuula; Halonen, Jaana I.; Aalto, Ville; Kivimaki, Mika; Vahtera, Jussi (2016)
    Background: Retirement is a major life transition which may affect lifestyle. The aim of this study is to examine within-individual changes in physical activity during the transition from full-time work to retirement. Methods: The study population consisted of 9,488 Finnish public-sector employees who retired in 2000-2011 and who reported their leisure-time and commuting physical activity before and after retirement. On average, participants provided data at 3.6 (of the four) repeat examinations during 10 years before and 10 years after the retirement. Physical activity was self-reported and was expressed as weekly metabolic equivalent task (MET) hours. Generalized estimating equations were used to examine physical activity trajectories around retirement. Results: Among participants entering to statutory retirement physical activity first increased by 1.81 MET-hours (95 % confidence interval [CI] 1.20 to 2.42) during 4-year retirement transition, but then decreased by -1.80 MET hours (95 % CI -2.83 to -0.79) during the subsequent post-retirement period. Older retirement age, higher occupational status and fewer chronic diseases were associated with greater increase in physical activity during transition to statutory retirement. Conclusions: Statutory retirement appears to be associated with a temporary increase in physical activity. Future research should examine ways to maintain the increased activity level after retirement.
  • Mikkola, T. M.; von Bonsdorff, M. B.; Osmond, C.; Salonen, M. K.; Kajantie, E.; Cooper, C.; Valimaki, M. J.; Eriksson, J. G. (2017)
    We examined the associations between childhood growth and bone properties among women at early old age. Early growth in height predicted greater bone area and higher bone mineral mass. However, information on growth did not improve prediction of bone properties beyond that predicted by body size at early old age. We examined the associations between body size at birth and childhood growth with bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) in early old age. A subgroup of women (n = 178, mean 60.4 years) from the Helsinki Birth Cohort Study, born 1934-1944, participated in dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and hip. Height and weight at 0, 2, 7, and 11 years, obtained from health care records, were reconstructed into conditional variables representing growth velocity independent of earlier growth. Weight was adjusted for corresponding height. Linear regression models were adjusted for multiple confounders. Birth length and growth in height before 7 years of age were positively associated with femoral neck area (p <0.05) and growth in height at all age periods studied with spine bone area (p <0.01). Growth in height before the age of 7 years was associated with BMC in the femoral neck (p <0.01) and birth length and growth in height before the age of 7 years were associated with BMC in the spine (p <0.05). After entering adult height into the models, nearly all associations disappeared. Weight gain during childhood was not associated with bone area or BMC, and aBMD was not associated with early growth. Optimal growth in height in girls is important for obtaining larger skeleton and consequently higher bone mass. However, when predicting bone mineral mass among elderly women, information on early growth does not improve prediction beyond that predicted by current height and weight.