Publications
2026
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Atlas of genetic architecture and exploratory temporal interaction networks of plasma protein-based organ and system aging
Organ-level investigations provide insights into inter-individual heterogeneity in health and disease, yet aging across organs and systems remains incompletely understood. Leveraging plasma proteomic data from 53,014 UK Biobank participants, we construct 16 organ- and system-specific aging clocks that show 5436 significant associations with 1059 diseases (i.e., 655 incident and 404 prevalent diseases) and widespread responses to 841 diverse environmental factors, highlighting organ-specific and... -
Aging in the air we breathe: Mechanisms and consequences of air pollution exposure for biological aging
Air pollution is the leading environmental cause of disease burden worldwide and is increasingly recognized as a potent driver of accelerated biological aging. Rather than acting through organ-specific toxicity alone, air pollutants appear to affect the fundamental hallmarks of aging itself, including oxidative stress, chronic inflammation, epigenetic dysregulation, telomere attrition, mitochondrial dysfunction, and cellular senescence. The pollutants of greatest concern are fine and ultrafine... -
Pre-diagnostic biomarkers and risk of stress-related disorders: a cohort study based on electronic health records
CONCLUSIONS: Hemoglobin, potassium, and LDL-C showed modest but robust associations with stress-related disorder diagnosis. These findings point to physiological domains for future research into the somatic aspects of stress-related disorders. -
Biological aging as a mediator of the association between air pollution and all-cause mortality and hospitalization: Evidence from the UK Biobank and Lifelines cohorts
Air pollution is a major environmental risk factor for premature mortality and hospitalization, yet the biological pathways linking pollution exposure to disease and mortality remain incompletely understood. We investigated whether biological aging mediates the effects of long-term air pollution exposure on mortality and hospitalizations using data from the UK Biobank (n = 309,467; aged 37-73 years) and the Lifelines (n = 29,146; aged 18-93 years). Long-term residential exposures to PM₂.₅, PM₁₀,... -
Plasma proteomic signature of frailty in 50,506 adults
Proteomics enables the systematic elucidation of biological mechanisms underlying frailty. Through a large proteome-wide association study of 2,911 plasma proteins from 50,506 UK Biobank participants, we identified 1,339 proteins significantly associated with frailty, highlighting collagen-containing extracellular matrix and vesicle lumen pathways. Replication in the TwinGene study confirmed partial but consistent associations. Mendelian randomization analyses identified five potentially causal... -
A blood-based metabolomics study of cardiovascular diseases in Swedish twins reveals apolipoprotein B biology as important for myocardial infarction
Cardiovascular diseases are the leading cause of death globally. Consequently, metabolomics studies have in recent years aimed at identifying relevant biomarkers, yet no studies have been performed in twin populations, which reduce confounding due to genetic and environmental factors. We included 11,217 twins (age at intake, 47-94 years (mean = 65)) from the Swedish Twin Registry, holding data on 173 nuclear magnetic resonance metabolomic biomarkers and nationwide register-based data on...
2025
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Identifying health conditions in older adults in textual health records using deep learning-based natural language processing
Many clinically significant health conditions in older adults are underreported or only recorded in unstructured health records. These records, however, contain valuable information for patient care and prognosis. This study utilized 10.6 million free-text entries from the electronic health records of 102,525 patients aged 50-80 across various care settings in Finland from 2010 to 2022. A deep learning-based natural language processing model was employed to perform named entity recognition (NER)... -
Cognitive Performance in Late Midlife as a Predictor of Frailty from Late Midlife into Old Age: A Longitudinal Birth Cohort Study
CONCLUSION: Poorer cognitive performance is associated with higher levels of frailty in late midlife. The association between cognitive performance and frailty from late midlife into old age was less consistent and varied by the cognitive trait being measured. -
Digital home-based multimodal prehabilitation of colorectal cancer patients prior to surgery (the dHOPE study): a non-inferiority clinical trial protocol
BACKGROUND: Cancer surgery is associated with risk of complications and loss of function. Vulnerability factors, such as advanced age, malnutrition, smoking, comorbidity, frailty, and low socioeconomic status increase the risk. Lifestyle intervention prior to surgery, known as prehabilitation, often include physical activity, nutritional support, psychological coaching, and smoking cessation, increase functional reserves and reduce postoperative complications. Most importantly, it prevents loss... -
Work-related stress and burnout: Is epigenetic aging the missing link?
CONCLUSIONS: Consequently, our results do not support the hypothesis that epigenetic aging serves as a biological mechanism linking work-related stress or biological stress markers to burnout symptoms. While work-related stress significantly predicts burnout and depressive symptoms, its association does not appear to be driven by epigenetic aging pathways in a low to moderately burdened population. These findings underscore the need for longer follow-up studies to explore alternative biological... -
The mediating role of epigenetic ageing in the nonlinear association between body mass index and survival: a prospective cohort analysis of the US Health and Retirement Study
BACKGROUND: The role of biological ageing in the association between body mass index (BMI) and survival remains unclear. We examined whether epigenetic age acceleration (EAA), a biomarker of biological ageing, mediates the BMI-survival association. -
Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty
Frailty is a clinically relevant phenotype with notable gaps in our understanding of its etiology. Using the Hospital Frailty Risk Score (HFRS) to define frailty, we performed a genome-wide association study in FinnGen (N = 500,737), replicated the results in the UK Biobank (N = 407,463) and performed a meta-analysis. We prioritized genes through colocalization with expression, splicing and protein quantitative trait loci and proteomics integration. We identified 53 independent lead variants... -
A Longitudinal Study of the Bidirectional Temporal Dynamics Between Body Mass Index and Biological Aging
CONCLUSIONS: Higher BMI predicted a steeper increase in FI, substantiating the hypothesis that obesity accelerates biological aging. Higher biological aging, measured as FI and FAI, drove a steeper BMI decline in late life, signalling that late-life weight loss may result from accelerated aging. Higher BMI may accelerate aspects of the aging process, and the aging process, in turn, accelerates late-life BMI decline, necessitating an integrated approach to manage both obesity and unintentional... -
Walking Speed and Risk of Cancer in Two Prospective Cohort Studies
CONCLUSION: Faster walking speed, whether self-reported or measured, is associated with a reduced risk of cancer development. This association appears to be partially mediated by lower inflammation and improved lipid profiles. -
Predicting cardiovascular morbidity and mortality with SCORE2 (OP) and Framingham risk estimates in combination with indicators of biological ageing
CONCLUSIONS: We show robust evidence that a higher FI value at baseline is associated with an increased risk of incident CVD in middle-aged and older CVD-free individuals, also when simultaneously considering the risk according to the FRS or SCORE2/SCORE2-OP. The FI improved the predictive accuracy of CVD outcomes beyond the traditional CVD risk indicators and demonstrated satisfactory predictive accuracy even when used independently. -
Factors associated with the development of severe asthma: A nationwide study (FINASTHMA)
CONCLUSION: The results provide a clinically relevant risk factor profile for early identification of the patients at risk of developing severe asthma. -
Marital and living status and biological ageing trajectories: a longitudinal cohort study with a 20-year follow-up
Biomarkers of ageing (BA) can predict health risks beyond chronological age, but little is known about how marital/living status affects longitudinal changes in BA. We examined the association between marital/living status and BA over time using the-Swedish-Adoption/Twin-Study-of-Aging (SATSA) cohort. Four BAs were analyzed: telomere length (TL) (638 individuals; 1603 measurements), DNAmAge (535 individuals; 1392 measurements), cognition (823 individuals; 3218 measurements), and frailty index... -
Genetic influences, lifestyle and psychosocial aspects in relation to metabolically healthy obesity and conversion to a metabolically unhealthy state
CONCLUSIONS: Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state. -
Defining an ageing-related pathology, disease or syndrome: International Consensus Statement
Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand... -
Association of cancer with functional decline at old age: a longitudinal study in Danish twins
INTRODUCTION: There is evidence that older adults with cancer have a higher risk of functional decline than cancer-free older adults. However, few studies are longitudinal, and none are twin studies. Thus, we aimed to investigate the relationship between cancer and functional decline in older adult (aged 70+ years) twins.
2024
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Older Adults With Celiac Disease Are At Increased Risk of Frailty: A Nationwide Cohort Study
INTRODUCTION: Celiac disease (CeD) is increasingly diagnosed in older adults, though few studies have explored complications in this group. As frailty confers increased risk for adverse events, we aimed to explore frailty in older adults with CeD. -
Genetic influences, lifestyle and psychosocial aspects in relation to metabolically healthy obesity and conversion to a metabolically unhealthy state
CONCLUSIONS: Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state. -
Defining an ageing-related pathology, disease or syndrome: International Consensus Statement
Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand... -
Is Cancer Associated With Frailty? Results From a Longitudinal Study of Old Danish Twins
CONCLUSIONS: We showed a higher risk of becoming frail following a cancer diagnosis in both discordant twin pairs and individual twins. These findings support the importance of monitoring frailty in older adults with cancer through geriatric assessments and the implementation of frailty interventions. -
Defining an Ageing-Related Pathology, Disease or Syndrome: International Consensus Statement
CONCLUSIONS: Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes. -
Frailty in Midlife as a Predictor of Changes in Body Composition from Midlife into Old Age: A Longitudinal Birth Cohort Study
CONCLUSIONS: We found evidence of an adverse health outcome of frailty where lean indices declined faster and fat indices and fat-to-lean ratios increased faster from midlife into old age. The changes resembled those that occurred with aging, but at a faster pace. The relationship between body composition and frailty is likely bidirectional, where high or increasing levels of fat are associated with the risk of becoming more frail earlier, but where a longer duration of frailty may increase the... -
Association of cancer with functional decline at old age: a longitudinal study in Danish twins
INTRODUCTION: There is evidence that older adults with cancer have a higher risk of functional decline than cancer-free older adults. However, few studies are longitudinal, and none are twin studies. Thus, we aimed to investigate the relationship between cancer and functional decline in older adult (aged 70+ years) twins. -
Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study
CONCLUSIONS: Lifestyle-related differences in frailty were already evident in late midlife and persisted into old age. Adopting one new healthy lifestyle-related factor had a small impact on a slightly less steeply increasing level of frailty. Maintaining regular exercise and sleeping habits may help prevent more rapid increases in frailty. -
Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden
Antihypertensive, lipid-lowering, and blood glucose-lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow-up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population-based studies collected between 1986 and 2014. Our exposures were the 21 most... -
Epigenome-wide analysis of frailty: Results from two European twin cohorts
Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index... -
Interplay of body mass index and metabolic syndrome: association with physiological age from midlife to late-life
Obesity and metabolic syndrome (MetS) share common pathophysiological characteristics with aging. To better understand their interplay, we examined how body mass index (BMI) and MetS jointly associate with physiological age, and if the associations changed from midlife to late-life. We used longitudinal data from 1,825 Swedish twins. Physiological age was measured as frailty index (FI) and functional aging index (FAI) and modeled independently in linear mixed-effects models adjusted for... -
Temporal Dynamics of Epigenetic Aging and Frailty From Midlife to Old Age
CONCLUSIONS: Our results highlight a temporal order between epigenetic aging and frailty such that changes in DunedinPACE precede changes in the FI. This potentially suggests that the pace of aging clock can be used as an early marker of the overall physiological decline at system level.
2023
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Pre-diagnostic biomarkers and risk of stress-related disorders: a cohort study based on electronic health records
CONCLUSIONS: Hemoglobin, potassium, and LDL-C showed modest but robust associations with stress-related disorder diagnosis. These findings point to physiological domains for future research into the somatic aspects of stress-related disorders. -
A Longitudinal Study of the Bidirectional Temporal Dynamics Between Body Mass Index and Biological Aging
CONCLUSIONS: Higher BMI predicted a steeper increase in FI, substantiating the hypothesis that obesity accelerates biological aging. Higher biological aging, measured as FI and FAI, drove a steeper BMI decline in late life, signalling that late-life weight loss may result from accelerated aging. Higher BMI may accelerate aspects of the aging process, and the aging process, in turn, accelerates late-life BMI decline, necessitating an integrated approach to manage both obesity and unintentional... -
Genetic influences, lifestyle and psychosocial aspects in relation to metabolically healthy obesity and conversion to a metabolically unhealthy state
CONCLUSIONS: Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state. -
Use of Electronic Medical Records (EMR) in Gerontology: Benefits, Considerations and a Promising Future
Electronic medical records (EMRs) have many benefits in clinical research in gerontology, enabling data analysis, development of prognostic tools and disease risk prediction. EMRs also offer a range of advantages in clinical practice, such as comprehensive medical records, streamlined communication with healthcare providers, remote data access, and rapid retrieval of test results, ultimately leading to increased efficiency, enhanced patient safety, and improved quality of care in gerontology,... -
Interplay of body mass index and metabolic syndrome: association with physiological age from midlife to late-life
Obesity and metabolic syndrome (MetS) share common pathophysiological characteristics with aging. To better understand their interplay, we examined how body mass index (BMI) and MetS jointly associate with physiological age, and if the associations changed from midlife to late-life. We used longitudinal data from 1,825 Swedish twins. Physiological age was measured as frailty index (FI) and functional aging index (FAI) and modeled independently in linear mixed-effects models adjusted for... -
Anticoagulant treatment and COVID-19 mortality among older adults living in nursing homes in Sweden
CONCLUSIONS: Both prevalent and incident use of ACs in prophylactic dosing was associated with reduced 28-day mortality among older individuals with COVID-19 in a NH setting. The effect was seen across age-strata and in women. The findings present new insight in best practice for individuals diagnosed with COVID-19 in the NH setting. -
Recent developments in frailty identification, management, risk factors and prevention: A narrative review of leading journals in geriatrics and gerontology
Frailty is an age-related clinical condition characterised by an increased susceptibility to stressors and an elevated risk of adverse outcomes such as mortality. In the light of global population ageing, the prevalence of frailty is expected to soar in coming decades. This narrative review provides critical insights into recent developments and emerging practices in frailty research regarding identification, management, risk factors, and prevention. We searched journals in the top two quartiles... -
Is Frailty Different in Younger Adults Compared to Old? Prevalence, Characteristics, and Risk Factors of Early-Life and Late-Life Frailty in Samples from Sweden and UK
CONCLUSION: Frailty is prevalent also in younger age groups (aged <65) but differs in some of its characteristics from the old. The risk factors of frailty are nevertheless largely similar for early-life and late-life frailty. -
Rare functional variants in the CRP and G6PC genes modify the relationship between obesity and serum C-reactive protein in white British population
CONCLUSION: PA mutation burdens in the CRP and G6PC genes are strongly associated with decreased serum CRP concentrations. As serum CRP and obesity are important predictors of cardiovascular risks in clinics, our observations suggest taking rare genetic factors into consideration might improve the delivery of precision medicine. -
Automated frailty scores: towards clinical implementation
No abstract -
Unraveling the metabolic underpinnings of frailty using multicohort observational and Mendelian randomization analyses
Identifying metabolic biomarkers of frailty, an age-related state of physiological decline, is important for understanding its metabolic underpinnings and developing preventive strategies. Here, we systematically examined 168 nuclear magnetic resonance-based metabolomic biomarkers and 32 clinical biomarkers for their associations with frailty. In up to 90,573 UK Biobank participants, we identified 59 biomarkers robustly and independently associated with the frailty index (FI). Of these, 34... -
Genetically and environmentally predicted obesity in relation to cardiovascular disease: a nationwide cohort study
BACKGROUND: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). -
Clinical biomarker-based biological aging and risk of cancer in the UK Biobank
CONCLUSIONS: Advanced BA quantified by clinical biomarkers is associated with increased risks of any cancer, lung cancer, and colorectal cancer. -
Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging
Aging is a major risk factor for many chronic diseases. This study aimed to examine the effects of antihypertensive, lipid-lowering, and antidiabetic drugs on biological aging. We included 672 participants and 2746 repeated measurements from the Swedish Adoption/Twin Study of Aging. Self-reported medicine uses were categorized into antidiabetic, antihypertensive, and lipid-lowering drugs. A total of 12 biomarkers for biological aging (BA biomarkers) were included as outcomes. Conditional... -
Can frailty scores predict the incidence of cancer? Results from two large population-based studies
While chronological age is the single biggest risk factor for cancer, it is less clear whether frailty, an age-related state of physiological decline, may also predict cancer incidence. We assessed the associations of frailty index (FI) and frailty phenotype (FP) scores with the incidence of any cancer and five common cancers (breast, prostate, lung, colorectal, melanoma) in 453,144 UK Biobank (UKB) and 36,888 Screening Across the Lifespan Twin study (SALT) participants, who aged 38-73 years and...