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1.  Walking Recovery after a Hip Fracture: A Prospective Follow-Up Study among Community-Dwelling over 60-Year Old Men and Women 
BioMed Research International  2014;2014:289549.
Purpose. Recovery of walking outdoors after hip fracture is important for equal participation in the community. The causes of poor recovery are not fully understood. This study investigates recovery of walking outdoors and associated determinants after hip fracture. Methods. A prospective follow-up study, among clinical sample of 81 community-dwelling hip fracture patients over 60 years. Perceived difficulty in walking outdoors and 500 meters was assessed before fracture, at discharge to home (3.2 ± 2.2 weeks after surgery), and on average 6.0 ± 3.3 weeks after discharge. Potential determinants for walking recovery were assessed. Linear latent trajectory model was used to analyse changes during follow-up. Association between walking trajectories and potential determinants was analysed with a logistic regression model. Results. Two trajectories, No-to-minor-difficulty and Catastrophic, were found. Thirty-eight percent of the participants ended up in the Catastrophic trajectory for walking outdoors and 67% for 500 meters. Multivariate logistic regression analysis revealed that use of walking aid and indoor falls before fracture and prolonged pain were independently associated with catastrophic decline in both primary outcomes: difficulty in walking outdoors and 500 meters. Conclusions. A large proportion of community-dwelling older people recovering from hip fracture experienced catastrophic decline in outdoor walking. Acknowledging recovery prognoses at early stage enables individualized rehabilitation.
doi:10.1155/2014/289549
PMCID: PMC3912885  PMID: 24511530
2.  Environmental barriers, person-environment fit and mortality among community-dwelling very old people 
BMC Public Health  2013;13:783.
Background
Environmental barriers are associated with disability-related outcomes in older people but little is known of the effect of environmental barriers on mortality. The aim of this study was to examine whether objectively measured barriers in the outdoor, entrance and indoor environments are associated with mortality among community-dwelling 80- to 89-year-old single-living people.
Methods
This longitudinal study is based on a sample of 397 people who were single-living in ordinary housing in Sweden. Participants were interviewed during 2002–2003, and 393 were followed up for mortality until May 15, 2012.
Environmental barriers and functional limitations were assessed with the Housing Enabler instrument, which is intended for objective assessments of Person-Environment (P-E) fit problems in housing and the immediate outdoor environment. Mortality data were gathered from the public national register. Cox regression models were used for the analyses.
Results
A total of 264 (67%) participants died during follow-up. Functional limitations increased mortality risk. Among the specific environmental barriers that generate the most P-E fit problems, lack of handrails in stairs at entrances was associated with the highest mortality risk (adjusted RR 1.55, 95% CI 1.14-2.10), whereas the total number of environmental barriers at entrances and outdoors was not associated with mortality. A higher number of environmental barriers indoors showed a slight protective effect against mortality even after adjustment for functional limitations (RR 0.98, 95% CI 0.96-1.00).
Conclusion
Specific environmental problems may increase mortality risk among very-old single-living people. However, the association may be confounded by individuals’ health status which is difficult to fully control for. Further studies are called for.
doi:10.1186/1471-2458-13-783
PMCID: PMC3765774  PMID: 23981906
ENABLE AGE-project; Environment; Mortality; Older people; Housing Enabler
3.  Effects of a Rehabilitation Program on Perceived Environmental Barriers in Older Patients Recovering from Hip Fracture: A Randomized Controlled Trial 
BioMed Research International  2013;2013:769645.
Objectives. To study effects of a one-year multicomponent intervention on perceived environmental barriers in hip fracture patients. Design. Randomized controlled trial of a 12-month home-based rehabilitation aiming to improve mobility and function (ISRCTN53680197); secondary analyses. Subjects. Community-dwelling hip fracture patients on average 70 days after trauma (n = 81). Methods. Assessments at baseline, 3, 6, and 12 months later included perceived entrance-related barriers (e.g., indoor/outdoor stairs, lighting, floor surfaces, and storage for mobility devices) and perceived barriers in the outdoor environment (poor street condition, hilly terrain, long-distances, and lack of resting places). Sum scores for entrance-related and outdoor barriers were analyzed using general estimating equation models. Results. At baseline, 48% and 37% of the patients perceived at least one entrance-related barrier, and 62% and 60% perceived at least one outdoor barrier in the intervention and control group, respectively. Over time, (P = 0.003) the number of entrance-related barriers decreased in both groups (group P = 0.395; interaction P = 0.571). For outdoor barriers, time (P = 0.199), group (P = 0.911), and interaction effect (P = 0.430) were not significant. Conclusion. Our intervention had no additional benefit over standard care in hip fracture patients. Further study is warranted to determine whether perceived environmental barriers can be reduced by interventions targeted at the older individual. This trial is registered with ISRCTN53680197.
doi:10.1155/2013/769645
PMCID: PMC3748419  PMID: 23986910
4.  Promoting Mobility in Older People 
Out-of-home mobility is necessary for accessing commodities, making use of neighborhood facilities, and participation in meaningful social, cultural, and physical activities. Mobility also promotes healthy aging as it relates to the basic human need of physical movement. Mobility is typically assessed either with standardized performance-based tests or with self-reports of perceived difficulty in carrying out specific mobility tasks. Mobility declines with increasing age, and the most complex and demanding tasks are affected first. Sometimes people cope with declining functional capacity by making changes in their way or frequency of doing these tasks, thus avoiding facing manifest difficulties. From the physiological point of view, walking is an integrated result of the functioning of the musculoskeletal, cardio-respiratory, sensory and neural systems. Studies have shown that interventions aiming to increase muscle strength will also improve mobility. Physical activity counseling, an educational intervention aiming to increase physical activity, may also prevent mobility decline among older people. Sensory deficits, such as poor vision and hearing may increase the risk of mobility decline. Consequently, rehabilitation of sensory functions may prevent falls and decline in mobility. To promote mobility, it is not enough to target only individuals because environmental barriers to mobility may also accelerate mobility decline among older people. Communities need to promote the accessibility of physical environments while also trying to minimize negative or stereotypic attitudes toward the physical activity of older people.
doi:10.3961/jpmph.2013.46.S.S50
PMCID: PMC3567319  PMID: 23413006
Aging; Walking; Motor activity; Muscle strength; Environmental barriers; Health promotion
5.  Individual and environmental factors underlying life space of older people – study protocol and design of a cohort study on life-space mobility in old age (LISPE) 
BMC Public Health  2012;12:1018.
Background
A crucial issue for the sustainability of societies is how to maintain health and functioning in older people. With increasing age, losses in vision, hearing, balance, mobility and cognitive capacity render older people particularly exposed to environmental barriers. A central building block of human functioning is walking. Walking difficulties may start to develop in midlife and become increasingly prevalent with age. Life-space mobility reflects actual mobility performance by taking into account the balance between older adults internal physiologic capacity and the external challenges they encounter in daily life. The aim of the Life-Space Mobility in Old Age (LISPE) project is to examine how home and neighborhood characteristics influence people’s health, functioning, disability, quality of life and life-space mobility in the context of aging. In addition, examine whether a person’s health and function influence life-space mobility.
Design
This paper describes the study protocol of the LISPE project, which is a 2-year prospective cohort study of community-dwelling older people aged 75 to 90 (n = 848). The data consists of a baseline survey including face-to-face interviews, objective observation of the home environment and a physical performance test in the participant’s home. All the baseline participants will be interviewed over the phone one and two years after baseline to collect data on life-space mobility, disability and participation restriction. Additional home interviews and environmental evaluations will be conducted for those who relocate during the study period. Data on mortality and health service use will be collected from national registers. In a substudy on walking activity and life space, 358 participants kept a 7-day diary and, in addition, 176 participants also wore an accelerometer.
Discussion
Our study, which includes extensive data collection with a large sample, provides a unique opportunity to study topics of importance for aging societies. A novel approach is employed which enables us to study the interactions of environmental features and individual characteristics underlying the life-space of older people. Potentially, the results of this study will contribute to improvements in strategies to postpone or prevent progression to disability and loss of independence.
doi:10.1186/1471-2458-12-1018
PMCID: PMC3534010  PMID: 23170987
Life-space; Mobility; Quality of life; Environment; Participation; Physical activity; Walking; Aging; Cohort studies
6.  Genetic architecture of circulating lipid levels 
Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.
doi:10.1038/ejhg.2011.21
PMCID: PMC3137496  PMID: 21448234
serum lipids; polygenic; genome-wide association; polygenic score; pathway analysis
7.  Job strain among blue-collar and white-collar employees as a determinant of total mortality: a 28-year population-based follow-up 
BMJ Open  2012;2(2):e000860.
Objectives
To investigate the effect of job demand, job control and job strain on total mortality among white-collar and blue-collar employees working in the public sector.
Design
28-year prospective population-based follow-up.
Setting
Several municipals in Finland.
Participants
5731 public sector employees from the Finnish Longitudinal Study on Municipal Employees Study aged 44–58 years at baseline.
Outcomes
Total mortality from 1981 to 2009 among individuals with complete data on job strain in midlife, categorised according to job demand and job control: high job strain (high job demands and low job control), active job (high job demand and high job control), passive job (low job demand and low job control) and low job strain (low job demand and high job control).
Results
1836 persons died during the follow-up. Low job control among men increased (age-adjusted HR 1.26, 95% CI 1.12 to 1.42) and high job demand among women decreased the risk for total mortality HR 0.82 (95% CI 0.71 to 0.95). Adjustment for occupational group, lifestyle and health factors attenuated the association for men. In the analyses stratified by occupational group, high job strain increased the risk of mortality among white-collar men (HR 1.52, 95% CI 1.09 to 2.13) and passive job among blue-collar men (HR 1.28, 95% CI 1.05 to 1.47) compared with men with low job strain. Adjustment for lifestyle and health factors attenuated the risks. Among white-collar women having an active job decreased the risk for mortality (HR 0.78, 95% CI 0.60 to 1.00).
Conclusion
The impact of job strain on mortality was different according to gender and occupational group among middle-aged public sector employees.
Article summary
Article focus
High job strain and its components, high job demand and low job control, predict cardiovascular and total mortality.
Although lower socioeconomic position is a risk factor for premature total mortality, few studies have explored the effect of job strain on mortality within socioeconomic groups and the ones that exist, report conflicting findings.
Key messages
In a population-based cohort of middle-aged public sector employees, low job control among men increased and high job demand among women decreased the risk of mortality during a 28-year follow-up.
High job strain increased the risk of mortality among white-collar men and passive job among blue-collar men compared with men with low job strain.
Active job among white-collar women decreased the risk for mortality compared with those with low job strain.
Strengths and limitations of this study
A major strength was the representative large sample of public sector employees working both in white-collar and blue-collar professions and the long follow-up time on mortality collected from the national mortality register.
A limitation is the self-reported job strain, however, high correlations between subjective and expert ratings on work conditions have been reported. The assessment of job strain was measured at a single time point in midlife which might imperfectly reflect long-term job strain, however, the municipal employees in our cohort had stable work histories indicating stability probably also for job strain during their earlier working life.
doi:10.1136/bmjopen-2012-000860
PMCID: PMC3307125  PMID: 22422919
8.  Association between Obesity History and Hand Grip Strength in Older Adults—Exploring the Roles of Inflammation and Insulin Resistance as Mediating Factors 
Background.
To examine the association between obesity history and hand grip strength, and whether the association is partly explained by subclinical inflammation and insulin resistance.
Methods.
Data are from 2,021 men and women aged 55 years and older participating in the representative population-based Health 2000 Survey in Finland. Body mass and body height, maximal hand grip strength, C-reactive protein, and insulin resistance based on homeostasis model assessment (HOMA-IR) were measured in a health examination. Recalled weight at 20, 30, 40, and 50 years of age were recorded to obtain a hierarchical classification of obesity history. Obesity was defined as body mass index ≥ 30 kg/m2.
Results.
Earlier onset of obesity was associated with lower hand grip strength (p < .001) after controlling for age, sex, education, smoking, alcohol use, physical activity, several chronic diseases, and current body weight. Based on adjusted logistic regression models, the odds (95% confidence interval) for very low relative hand grip strength were 2.76 (1.78–4.28) for currently obese, 5.57 (3.02–10.28) for obese since age of 50 years, 6.53 (2.98–14.30) for obese since age of 40 years, and 10.36 (3.55–30.24) for obese since age of 30 years compared with never obese participants. The associations remained highly significant even after adjusting for current C-reactive protein and HOMA-IR, but these variables had only minor role in explaining the association between obesity history and hand grip strength.
Conclusions.
Long-term exposure to obesity is associated with poor hand grip strength later in life. Maintaining healthy body weight throughout the life span may help to maintain adequate muscle strength in old age. Prospective studies with information on prior muscle strength are needed to examine in detail the causal association between obesity history and muscle strength.
doi:10.1093/gerona/glq226
PMCID: PMC3041473  PMID: 21310808
Muscle strength; Obesity; Inflammation; Insulin resistance; Aging
9.  Promoting mobility after hip fracture (ProMo): study protocol and selected baseline results of a year-long randomized controlled trial among community-dwelling older people 
Background
To cope at their homes, community-dwelling older people surviving a hip fracture need a sufficient amount of functional ability and mobility. There is a lack of evidence on the best practices supporting recovery after hip fracture. The purpose of this article is to describe the design, intervention and demographic baseline results of a study investigating the effects of a rehabilitation program aiming to restore mobility and functional capacity among community-dwelling participants after hip fracture.
Methods/Design
Population-based sample of over 60-year-old community-dwelling men and women operated for hip fracture (n = 81, mean age 79 years, 78% were women) participated in this study and were randomly allocated into control (Standard Care) and ProMo intervention groups on average 10 weeks post fracture and 6 weeks after discharged to home. Standard Care included written home exercise program with 5-7 exercises for lower limbs. Of all participants, 12 got a referral to physiotherapy. After discharged to home, only 50% adhered to Standard Care. None of the participants were followed-up for Standard Care or mobility recovery. ProMo-intervention included Standard Care and a year-long program including evaluation/modification of environmental hazards, guidance for safe walking, pain management, progressive home exercise program and physical activity counseling. Measurements included a comprehensive battery of laboratory tests and self-report on mobility limitation, disability, physical functional capacity and health as well as assessments for the key prerequisites for mobility, disability and functional capacity. All assessments were performed blinded at the research laboratory. No significant differences were observed between intervention and control groups in any of the demographic variables.
Discussion
Ten weeks post hip fracture only half of the participants were compliant to Standard Care. No follow-up for Standard Care or mobility recovery occurred. There is a need for rehabilitation and follow-up for mobility recovery after hip fracture. However, the effectiveness of the ProMo program can only be assessed at the end of the study.
Trial registration
Current Controlled Trials ISRCTN53680197
doi:10.1186/1471-2474-12-277
PMCID: PMC3295703  PMID: 22145912
10.  A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol 
Surakka, Ida | Isaacs, Aaron | Karssen, Lennart C. | Laurila, Pirkka-Pekka P. | Middelberg, Rita P. S. | Tikkanen, Emmi | Ried, Janina S. | Lamina, Claudia | Mangino, Massimo | Igl, Wilmar | Hottenga, Jouke-Jan | Lagou, Vasiliki | van der Harst, Pim | Mateo Leach, Irene | Esko, Tõnu | Kutalik, Zoltán | Wainwright, Nicholas W. | Struchalin, Maksim V. | Sarin, Antti-Pekka | Kangas, Antti J. | Viikari, Jorma S. | Perola, Markus | Rantanen, Taina | Petersen, Ann-Kristin | Soininen, Pasi | Johansson, Åsa | Soranzo, Nicole | Heath, Andrew C. | Papamarkou, Theodore | Prokopenko, Inga | Tönjes, Anke | Kronenberg, Florian | Döring, Angela | Rivadeneira, Fernando | Montgomery, Grant W. | Whitfield, John B. | Kähönen, Mika | Lehtimäki, Terho | Freimer, Nelson B. | Willemsen, Gonneke | de Geus, Eco J. C. | Palotie, Aarno | Sandhu, Manj S. | Waterworth, Dawn M. | Metspalu, Andres | Stumvoll, Michael | Uitterlinden, André G. | Jula, Antti | Navis, Gerjan | Wijmenga, Cisca | Wolffenbuttel, Bruce H. R. | Taskinen, Marja-Riitta | Ala-Korpela, Mika | Kaprio, Jaakko | Kyvik, Kirsten O. | Boomsma, Dorret I. | Pedersen, Nancy L. | Gyllensten, Ulf | Wilson, James F. | Rudan, Igor | Campbell, Harry | Pramstaller, Peter P. | Spector, Tim D. | Witteman, Jacqueline C. M. | Eriksson, Johan G. | Salomaa, Veikko | Oostra, Ben A. | Raitakari, Olli T. | Wichmann, H.-Erich | Gieger, Christian | Järvelin, Marjo-Riitta | Martin, Nicholas G. | Hofman, Albert | McCarthy, Mark I. | Peltonen, Leena | van Duijn, Cornelia M. | Aulchenko, Yurii S. | Ripatti, Samuli | Gibson, Greg
PLoS Genetics  2011;7(10):e1002333.
Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene–environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10−9. There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
Author Summary
Circulating serum lipids contribute greatly to the global health by affecting the risk for cardiovascular diseases. Serum lipid levels are partly inherited, and already 95 loci affecting high- and low-density lipoprotein cholesterol, total cholesterol, and triglycerides have been found. Serum lipids are also known to be affected by multiple epidemiological risk factors like body composition, lifestyle, and sex. It has been hypothesized that there are loci modifying the effects between risk factors and serum lipids, but to date only candidate gene studies for interactions have been reported. We conducted a genome-wide screen with meta-analysis approach to identify loci having interactions with epidemiological risk factors on serum lipids with over 30,000 population-based samples. When combining results from our initial datasets and 8 additional replication cohorts (maximum N = 17,102), we found a genome-wide significant locus in chromosome 4p15 with a joint P-value of 4.79×10−9 modifying the effect of waist-to-hip ratio on total cholesterol. In the area surrounding this genetic variant, there were two genes having association between the genotypes and the gene expression in adipose tissue, and we also found enrichment of association in genes belonging to lipid metabolism related functions.
doi:10.1371/journal.pgen.1002333
PMCID: PMC3197672  PMID: 22028671
11.  Hand-Grip Strength Cut-Points to Screen Older Persons at Risk for Mobility Limitation 
Objectives
To determine optimal hand-grip strength cut-points for increased likelihood for mobility limitation among older people and to study whether these cut-points differ according to body mass index (BMI).
Design and setting
Cross-sectional analysis of data collected in the Finnish population-based Health 2000 Survey.
Participants and measurements
1 084 men and 1 562 women aged 55 years and older with complete data on anthropometry, hand-grip strength and self-reported mobility. Mobility limitation was defined as difficulties in walking 0.5-km or climbing stairs. Receiver Operating Characteristics analysis was used to estimate hand-grip strength cut-points for increased likelihood for mobility limitation.
Results
The overall hand-grip strength cut-points for increased likelihood for mobility limitation were 37 kg (sensitivity 62% and specificity 76%) for men and 21 kg (67% and 73%) for women. Hand-grip strength by BMI interaction on mobility limitation was significant among men (p = 0.022), while no such interaction was observed among women (p = 0.156). Among men, most optimal cut-offs were 33 kg (73% and 79%) for normal-weight men, 39 kg (67% and 71%) for overweight men and 40 kg (57% and 68%) for obese men. Among women, BMI-specific hand-grip strength cut-off values did not markedly increase accuracy over the overall cut-off value.
Conclusion
Hand-grip strength test is a useful tool to identify persons with increased risk for mobility limitation. Among men, the hand-grip strength cut-points for mobility increased along with BMI, while among women only one hand-grip strength threshold was identified.
doi:10.1111/j.1532-5415.2010.03035.x
PMCID: PMC2946262  PMID: 20863331
muscle strength; functional capacity; mobility; body mass index; ROC analysis
12.  Midlife muscle strength and human longevity up to age 100 years: a 44-year prospective study among a decedent cohort 
Age  2011;34(3):563-570.
We studied prospectively the midlife handgrip strength, living habits, and parents’ longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu–Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965–1968, when they were 56–68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment. Longevity was categorized as centenarian (≥100 years, n = 47), nonagenarian (90–99 years, n = 545), octogenarian (80–89 years, n = 847), and ≤79 years (n = 801, reference). The average survival after baseline was 20.8 years (SD = 9.62). Compared with people who died at the age of ≤79 years, centenarians belonged 2.5 times (odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23–5.10) more often to the highest third of grip strength in midlife, were never smokers (OR = 5.75 95% CI = 3.06–10.80), had participated in physical activity outside work (OR = 1.13 per daily hour, 95% CI = 1.02–1.25), and had a long-lived mother (≥80 vs. ≤60 years, OR = 2.3, 95% CI = 1.06–5.01). Associations for nonagenarians and octogenarians were parallel, but weaker. Multivariate modeling showed that mother’s longevity and offspring’s grip strength operated through the same or overlapping pathway to longevity. High midlife grip strength and long-lived mother may indicate resilience to aging, which, combined with healthy lifestyle, increases the probability of extreme longevity.
doi:10.1007/s11357-011-9256-y
PMCID: PMC3337929  PMID: 21541735
Aging; Longevity; Inter-generational; Grip strength; Mortality; Human; Life Sciences; Molecular Medicine; Geriatrics/Gerontology; Cell Biology
13.  Work ability in midlife as a predictor of mortality and disability in later life: a 28-year prospective follow-up study 
Background
Poor work ability correlates with increased morbidity and early retirement from the workforce, but the association in old age is not known. We investigated work ability in midlife among white-collar and blue-collar employees as a predictor of mortality and disability 28 years later.
Methods
A total of 5971 occupationally active people aged 44–58 years participated in the Finnish Longitudinal Study of Municipal Employees (FLAME) in 1981. Perceived work ability relative to lifetime best was categorized as excellent, moderate or poor. In 2009, the ability to perform activities of daily living was assessed among 2879 respondents (71.0% of the survivors). Mortality data were available up to July 2009.
Results
At the 28-year follow-up, 1918 of the 5971 participants had died and 1403 had some form of disability. Rates of death per 1000 person-years among white-collar men were 7.7 for those with excellent work ability, 14.7 for those with moderate work ability and 23.5 for those with poor work ability. Among blue-collar men, the corresponding rates were 15.5, 20.2 and 25.3. In women, rates ranged between 6.3 and 10.6 per 1000 person-years. The age-adjusted hazard ratios (HRs) for mortality were two to three times higher among blue-collar male employees with lower work ability than among white-collar male employees with excellent work ability in midlife (i.e., the reference group). The odds of death or disability at follow-up compared with white-collar workers with excellent work ability were highest among blue-collar employees with poor work ability in midlife (odds ratio [OR] 4.56, 95% confidence interval [CI] 2.82–7.37 for men; OR 3.37, 95% CI 2.28–4.98 for women). Among the survivors, similar but slightly lower risks of disability 28 years later were found.
Interpretation
Perceived poor work ability in midlife was associated with accelerated deterioration in health and functioning and remains evident after 28 years of follow-up.
doi:10.1503/cmaj.100713
PMCID: PMC3050972  PMID: 21282315
14.  Genome-wide association study identifies five loci associated with lung function 
Repapi, Emmanouela | Sayers, Ian | Wain, Louise V | Burton, Paul R | Johnson, Toby | Obeidat, Ma’en | Zhao, Jing Hua | Ramasamy, Adaikalavan | Zhai, Guangju | Vitart, Veronique | Huffman, Jennifer E | Igl, Wilmar | Albrecht, Eva | Deloukas, Panos | Henderson, John | Granell, Raquel | McArdle, Wendy L | Rudnicka, Alicja R | Barroso, Inês | Loos, Ruth J F | Wareham, Nicholas J | Mustelin, Linda | Rantanen, Taina | Surakka, Ida | Imboden, Medea | Wichmann, H Erich | Grkovic, Ivica | Jankovic, Stipan | Zgaga, Lina | Hartikainen, Anna-Liisa | Peltonen, Leena | Gyllensten, Ulf | Johansson, Åsa | Zaboli, Ghazal | Campbell, Harry | Wild, Sarah H | Wilson, James F | Gläser, Sven | Homuth, Georg | Völzke, Henry | Mangino, Massimo | Soranzo, Nicole | Spector, Tim D | Polašek, Ozren | Rudan, Igor | Wright, Alan F | Heliövaara, Markku | Ripatti, Samuli | Pouta, Anneli | Naluai, Åsa Torinsson | Olin, Anna-Carin | Torén, Kjell | Cooper, Matthew N | James, Alan L | Palmer, Lyle J | Hingorani, Aroon D | Wannamethee, S Goya | Whincup, Peter H | Smith, George Davey | Ebrahim, Shah | McKeever, Tricia M | Pavord, Ian D | MacLeod, Andrew K | Morris, Andrew D | Porteous, David J | Cooper, Cyrus | Dennison, Elaine | Shaheen, Seif | Karrasch, Stefan | Schnabel, Eva | Schulz, Holger | Grallert, Harald | Bouatia-Naji, Nabila | Delplanque, Jérôme | Froguel, Philippe | Blakey, John D | Britton, John R | Morris, Richard W | Holloway, John W | Lawlor, Debbie A | Hui, Jennie | Nyberg, Fredrik | Jarvelin, Marjo-Riitta | Jackson, Cathy | Kähönen, Mika | Kaprio, Jaakko | Probst-Hensch, Nicole M | Koch, Beate | Hayward, Caroline | Evans, David M | Elliott, Paul | Strachan, David P | Hall, Ian P | Tobin, Martin D
Nature genetics  2009;42(1):36-44.
Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
doi:10.1038/ng.501
PMCID: PMC2862965  PMID: 20010834
15.  Hearing as a Predictor of Falls and Postural Balance in Older Female Twins 
Background
The purpose of the present study was to examine, first, whether hearing acuity predicts falls and whether the potential association is explained by postural balance and, second, to examine whether shared genetic or environmental effects underlie these associations.
Methods
Hearing was measured using a clinical audiometer as a part of the Finnish Twin Study on Aging in 103 monozygotic and 114 dizygotic female twin pairs aged 63–76 years. Postural balance was indicated as a center of pressure (COP) movement in semitandem stance, and participants filled in a fall-calendar daily for an average of 345 days after the baseline.
Results
Mean hearing acuity (better ear hearing threshold level at 0.5–4 kHz) was 21 dB (standard deviation [SD] 12). Means of the COP velocity moment for the best to the poorest hearing quartiles increased linearly from 40.7 mm2/s (SD 24.4) to 52.8 mm2/s (SD 32.0) (p value for the trend = .003). Altogether 199 participants reported 437 falls. Age-adjusted incidence rate ratios (IRRs) for falls, with the best hearing quartile as a reference, were 1.2 (95% confidence interval [CI] = 0.4–3.8) in the second, 4.1 (95% CI = 1.1–15.6) in the third, and 3.4 (95% CI = 1.0–11.4) in the poorest hearing quartiles. Adjustment for COP velocity moment decreased IRRs markedly. Twin analyses showed that the association between hearing acuity and postural balance was not explained by genetic factors in common for these traits.
Conclusion
People with poor hearing acuity have a higher risk for falls, which is partially explained by their poorer postural control. Auditory information about environment may be important for safe mobility.
doi:10.1093/gerona/gln015
PMCID: PMC2655032  PMID: 19182227
Hearing; Postural balance; Fall; Twin study; Heritability; Aging
16.  Long-term Effect of Physical Activity Counseling on Mobility Limitation Among Older People: A Randomized Controlled Study 
Background
Physical activity counseling increases physical activity among older people, but its effectiveness on mobility, that is, maintaining the ability to move independently, is unknown. We studied the effect of physical activity counseling on mobility among older people and evaluated whether counseling-induced benefits persist after cessation of the intervention.
Methods
In a 2-year, single-blinded, randomized controlled study, 632 sedentary participants aged 75–81 years were randomly assigned into the intervention (n = 318) or control (n = 314) group. The intervention group received a single individualized physical activity counseling session with a supportive telephone contact every 4 months for 2 years. The outcome measures—perceived difficulty in advanced (walking 2 km) and basic (walking 0.5 km) mobility—were gathered semiannually during the intervention and the 1.5-year postintervention follow-up.
Results
The proportion of participants with difficulties in advanced mobility at the beginning and end of the intervention was 34% and 38%, respectively, in the intervention group. In the control group, the corresponding proportions were 32% and 45%. The treatment effect was significant at the 2-year follow-up (odds ratio [OR] 0.84, 95% confidence interval [CI]: 0.70–0.99; p = .04) and remained significant 1.5 years postintervention (OR 0.82, 95% CI: 0.68–0.99; p = .04). The effect on basic mobility postintervention was parallel but nonsignificant (OR 0.87, CI: 0.69–1.09; p = .22).
Conclusions
Among older people, a single individualized physical activity counseling session with a supportive phone contact every 4 months for 2 years had a positive effect on mobility, an important factor for maintaining independence in the community in old age.
doi:10.1093/gerona/gln029
PMCID: PMC2691194  PMID: 19164270
Aging; Disability; Mobility limitation; Physical activity; Promotion
17.  Effects of Long-Term Physical Activity on Cardiac Structure and Function: A Twin Study 
Previous studies have shown that athletic training or other physical activity causes structural and functional adaptations in the heart, but less is known how long-term physical activity affects heart when genetic liability and childhood environment are taken into account. The aim of this study was to investigate the effects of long-term physical activity vs. inactivity on cardiac structure and function in twin pairs discordant for physical activity for 32 years. Twelve same-sex twin pairs (five monozygotic and seven dizygotic, 50-67 years) were studied as a part of the TWINACTIVE study. Discordance in physical activity was initially determined in 1975 and it remained significant throughout the follow-up. At the end of the follow-up in 2007, resting echocardiographic and electrocardiographic measurements were performed. During the follow-up period, the active co-twins were on average 8.2 (SD 4.0) MET hours/day more active than their inactive co-twins (p < 0.001). At the end of the follow-up, resting heart rate was lower in the active than inactive co-twins [59 (SD 5) vs. 68 (SD 10) bpm, p=0.03]. The heart rate-corrected QT interval was similar between the co-twins. Also, there was a tendency for left ventricular mass per body weight to be greater and T wave amplitude in lead II to be higher in the active co-twins (18% and 15%, respectively, p=0.08 for both). Similar trends were found for both monozygotic and dizygotic twin pairs. In conclusion, the main adaptation to long- term physical activity is lowered resting heart rate, even after partially or fully controlling for genetic liability and childhood environment.
Key pointsThe main adaptation to long-term physical activity is lowering of resting heart rate, even after controlling for genetic liability.VO2peak is increased in the active co-twins compared with their inactive co-twins and accordingly, also submaximal heart rates during the clinical exercise test are lower in physically active co-twins.There is a tendency for increased LVM per body weight and heightened T wave amplitude in the active co-twins.
PMCID: PMC3761543  PMID: 24149594
Exercise; echocardiography; electrocardiography; heart rate; controlling for genetic liability; longitudinal study
18.  Sarcopenic obesity - definition, etiology and consequences 
Purpose of the review
Older obese persons with decreased muscle mass or strength are at special risk for adverse outcomes. We discuss potential pathways to muscle impairment in obese individuals and the consequences that joint obesity and muscle impairment may have on health and disability. Tantamount to this discussion is whether low muscle mass or, rather, muscle weakness should be used for the definition.
Recent findings
Excess energy intake, physical inactivity, low-grade inflammation, insulin resistance and changes in hormonal milieu may lead to the development of so called ‘sarcopenic obesity’. It was originally believed that the culprit of age-related muscle weakness was a reduction in muscle mass, but it is now clear that changes in muscle composition and quality are predominant. We propose that the risk of adverse outcomes, such as functional limitation and mortality, is better estimated by considering jointly obesity and muscle strength rather than obesity and muscle mass and the term “sarcopenic obesity” should be revisited.
Summary
Recognition of obese patients who have associated muscle problems is an essential goal for clinicians. Further research is needed to identify new target for prevention and cure of this important geriatric syndrome.
doi:10.1097/MCO.0b013e328312c37d
PMCID: PMC2633408  PMID: 18827572
adipose tissue; body composition; disability; muscle strength; obesity; older people; sarcopenia
19.  Catechol-O-Methyltransferase Gene Polymorphism Is Associated with Skeletal Muscle Properties in Older Women Alone and Together with Physical Activity 
PLoS ONE  2008;3(3):e1819.
Background
Muscle strength declines on average by one percent annually from midlife on. In postmenopausal women this decrement coincides with a rapid decline in estrogen production. The genetics underlying the effects of estrogen on skeletal muscle remains unclear. In the present study, we examined whether polymorphisms within COMT and ESR1 are associated with muscle properties and assessed their interaction and their combined effects with physical activity.
Methodology/Principal Findings
A cross-sectional data analysis was conducted with 434 63-76-year-old women from the population-based Finnish Twin Study on Aging. Body anthropometry, muscle cross-sectional area (mCSA), isometric hand grip and knee extension strengths, and leg extension power were measured. COMT Val158Met and ESR1 PvuII genotypes were determined by the RFLP method. mCSA differed by COMT genotypes (p = 0.014) being significantly larger in LL than HL individuals in unadjusted (p = 0.001) and age- and height-adjusted model (p = 0.004). When physical activity and age were entered into GEE model, COMT genotype had a significant main effect (p = 0.038) on mCSA. Furthermore, sedentary individuals with the HH genotype had lower muscle mass, strength and power, but they also appeared to benefit the most from physical activity. No association of ESR1 PvuII polymorphism with any of the muscle outcomes was observed.
Conclusions/Significance
The present study suggests that the COMT polymorphism, affecting the activity of the enzyme, is associated with muscle mass. Furthermore, sedentary individuals with potential high enzyme activity were the weakest group, but they may potentially benefit the most from physical activity. This observation elucidates the importance of both environmental and genetic factors in muscle properties.
doi:10.1371/journal.pone.0001819
PMCID: PMC2265555  PMID: 18350156

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