A geroscientific approach to study human biological aging

Human biological aging is characterized by a gradual loss of function and increased susceptibility to chronic diseases. Understanding the biological mechanisms that are driving these processes and identify factors that may slow them down have the potential to compress morbidity at the end of life and increase the healthy years with significant individual benefits and large societal impact.

Project leader

Sara Hägg

Principal researcher

Research program

My research program is built on the geroscience paradigm that advanced biological aging poses an increased risk of developing age-related diseases. By understanding causal mechanisms in human aging and identify geroprotectors we may prevent many conditions at once, leading to a longer healthy life. Hence, the overall objective of my research is to use large cohort data to perform epidemiological studies of aging and age-related diseases to advance our understanding of human biological aging. Towards this, several aims are proposed:

Figure. Overview of the research program “A geroscientific approach to study human biological aging” and the three different aims.
Figure. Overview of the research program “A geroscientific approach to study human biological aging” and the three different aims.

Aim 1. To investigate how different biomarkers of aging (e.g., telomere length, epigenetic clock, frailty, functional aging, cognitive decline, blood biomarkers, markers of brain aging, metabolites and proteins) are associated with age-related traits and mortality.

Some of the research questions are:

  • How can we reliably measure biological aging in humans?
  • How do different biological age measurements relate to each other?
  • Are they associated with age-related traits and mortality?
  • Can we track biological aging longitudinally?
  • What are the shared familial factors on biological aging?
  • Can we identify individuals with accelerated aging for prediction or prognosis of a disease?

Aim 2. To study the impact of genetics on aging and age-related traits.

Some of the research questions are:

  • Is there evidence for causality in associations between markers of biological age and age-related traits?
  • Can we identify novel genetic variants associated with biological aging and age-related traits?
  • What is the influence of genetic risk on aging trajectories and age-related traits?
  • Can genetic stratification, e.g., APOE ε4-carriers, CYP1A2 1A-carriers, identify individuals with adverse treatment outcome or at increased risk of disease?
  • Can we use polygenic risk scores for prediction or prognosis of an age-related disease?
  • How do genetic and environmental factors interact to influence biological aging and age-related traits?

Aim 3. To identify drugs that are useful to repurpose for age-related diseases using causal inference methods on epidemiological data.

Some of the research questions are:

  • What drugs may affect biological aging in humans?
  • Can drugs that influence biological aging be repurposed for other age-related diseases?
  • Can we perform and optimize emulated target trials using twin registry data?
  • Can we use a personalized medicine approach, e.g., include genetic and biological information, to identify individuals who may benefit more from drug repurposing?

Samples

Data used for conducting the research originate from several different cohorts and sources. For example, the Swedish Twin Registry (STR: https://ki.se/en/research/the-swedish-twin-registry), including longitudinal cohorts of aging such as SATSA, Gender, OCTO-Twin, Harmony, SALT and TwinGene. Other longitudinal cohorts of aging are included from the National E-infrastructure for Aging Research (NEAR) in Sweden. Moreover, I use the large-scale population-based UK Biobank cohort for many projects, in particular for genetic analyses. Here, we also use publicly available genetic data.

Publications

COVID vaccination in older adults.
Hägg S, Religa D
Nat Microbiol 2022 Aug;7(8):1106-1107

Genetics of age-at-onset in major depression.
Harder A, Nguyen TD, Pasman JA, Mosing MA, Hägg S, Lu Y
Transl Psychiatry 2022 Mar;12(1):124

A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking.
Higgins-Chen AT, Thrush KL, Wang Y, Minteer CJ, Kuo PL, Wang M, Niimi P, Sturm G, Lin J, Moore AZ, Bandinelli S, Vinkers CH, Vermetten E, Rutten BPF, Geuze E, Okhuijsen-Pfeifer C, van der Horst MZ, Schreiter S, Gutwinski S, Luykx JJ, Picard M, Ferrucci L, Crimmins EM, Boks MP, Hägg S, Hu-Seliger TT, Levine ME
Nat Aging 2022 Jul;2(7):644-661

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.
Howe LJ, Nivard MG, Morris TT, Hansen AF, Rasheed H, Cho Y, Chittoor G, Ahlskog R, Lind PA, Palviainen T, van der Zee MD, Cheesman R, Mangino M, Wang Y, Li S, Klaric L, Ratliff SM, Bielak LF, Nygaard M, Giannelis A, Willoughby EA, Reynolds CA, Balbona JV, Andreassen OA, Ask H, Baras A, Bauer CR, Boomsma DI, Campbell A, Campbell H, Chen Z, Christofidou P, Corfield E, Dahm CC, Dokuru DR, Evans LM, de Geus EJC, Giddaluru S, Gordon SD, Harden KP, Hill WD, Hughes A, Kerr SM, Kim Y, Kweon H, Latvala A, Lawlor DA, Li L, Lin K, Magnus P, Magnusson PKE, Mallard TT, Martikainen P, Mills MC, Njølstad PR, Overton JD, Pedersen NL, Porteous DJ, Reid J, Silventoinen K, Southey MC, Stoltenberg C, Tucker-Drob EM, Wright MJ, , , Hewitt JK, Keller MC, Stallings MC, Lee JJ, Christensen K, Kardia SLR, Peyser PA, Smith JA, Wilson JF, Hopper JL, Hägg S, Spector TD, Pingault JB, Plomin R, Havdahl A, Bartels M, Martin NG, Oskarsson S, Justice AE, Millwood IY, Hveem K, Naess Ø, Willer CJ, Åsvold BO, Koellinger PD, Kaprio J, Medland SE, Walters RG, Benjamin DJ, Turley P, Evans DM, Davey Smith G, Hayward C, Brumpton B, Hemani G, Davies NM
Nat Genet 2022 May;54(5):581-592

Response to Letter to the Editor: Comment on "Body mass index and Mini Nutritional Assessment-Short Form as predictors of in-geriatric hospital mortality in older adults with COVID-19" (by Café Balcı, MD, Hacettepe University Faculty of Medicine Department of Internal Medicine Division of Geriatric Medicine).
Kananen L, Religa D, Eriksdotter M, Hägg S, Julhävä J, Cederholm T
Clin Nutr 2022 Feb;41(2):573-574

Adiposity and the risk of dementia: mediating effects from inflammation and lipid levels.
Karlsson IK, Zhan Y, Wang Y, Li X, Jylhävä J, Hägg S, Dahl Aslan AK, Gatz M, Pedersen NL, Reynolds CA
Eur J Epidemiol 2022 Oct;():

Two Years with COVID-19: The Electronic Frailty Index Identifies High-Risk Patients in the Stockholm GeroCovid Study.
Mak JKL, Eriksdotter M, Annetorp M, Kuja-Halkola R, Kananen L, Boström AM, Kivipelto M, Metzner C, Bäck Jerlardtz V, Engström M, Johnson P, Lundberg LG, Åkesson E, Sühl Öberg C, Olsson M, Cederholm T, Hägg S, Religa D, Jylhävä J
Gerontology 2022 Nov;():1-10

Development of an Electronic Frailty Index for Hospitalized Older Adults in Sweden.
Mak JKL, Hägg S, Eriksdotter M, Annetorp M, Kuja-Halkola R, Kananen L, Boström AM, Kivipelto M, Metzner C, Bäck Jerlardtz V, Engström M, Johnson P, Lundberg LG, Åkesson E, Sühl Öberg C, Olsson M, Cederholm T, Jylhävä J, Religa D
J Gerontol A Biol Sci Med Sci 2022 Nov;77(11):2311-2319

Genetic and environmental influences on longitudinal frailty trajectories from adulthood into old age.
Mak JKL, Kuja-Halkola R, Bai G, Hassing LB, Pedersen NL, Hägg S, Jylhävä J, Reynolds CA
J Gerontol A Biol Sci Med Sci 2022 Sep;():

The association between mitochondrial DNA abundance and stroke: A combination of multivariable-adjusted survival and Mendelian randomization analyses.
Martens LG, Luo J, Wermer MJH, Willems van Dijk K, Hägg S, Grassmann F, Noordam R, van Heemst D
Atherosclerosis 2022 Aug;354():1-7

Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues.
Marttila S, Tamminen H, Rajić S, Mishra PP, Lehtimäki T, Raitakari O, Kähönen M, Kananen L, Jylhävä J, Hägg S, Delerue T, Peters A, Waldenberger M, Kleber ME, März W, Luoto R, Raitanen J, Sillanpää E, Laakkonen EK, Heikkinen A, Ollikainen M, Raitoharju E
Epigenomics 2022 Sep;14(18):1105-1124

Genetic heterogeneity and subtypes of major depression.
Nguyen TD, Harder A, Xiong Y, Kowalec K, Hägg S, Cai N, Kuja-Halkola R, Dalman C, Sullivan PF, Lu Y
Mol Psychiatry 2022 Mar;27(3):1667-1675

Dynamic patterns of blood lipids and DNA methylation in response to statin therapy.
Qin X, Wang Y, Pedersen NL, Tang B, Hägg S
Clin Epigenetics 2022 Nov;14(1):153

Reciprocal interaction between depression and pain: results from a comprehensive bidirectional Mendelian randomization study and functional annotation analysis.
Tang B, Meng W, Hägg S, Burgess S, Jiang X
Pain 2022 Jan;163(1):e40-e48

Genetic Variation in Targets of Antidiabetic Drugs and Alzheimer Disease Risk: A Mendelian Randomization Study.
Tang B, Wang Y, Jiang X, Thambisetty M, Ferrucci L, Johnell K, Hägg S
Neurology 2022 Aug;99(7):e650-e659

Protein Nutritional Status and Frailty: A Mendelian Randomization Study.
Tomata Y, Wang Y, Hägg S, Jylhävä J
J Nutr 2022 Jan;152(1):269-275

Assessment of the bi-directional relationship between blood mitochondrial DNA copy number and type 2 diabetes mellitus: a multivariable-adjusted regression and Mendelian randomisation study.
Wang W, Luo J, Willems van Dijk K, Hägg S, Grassmann F, T Hart LM, van Heemst D, Noordam R
Diabetologia 2022 Oct;65(10):1676-1686

Gender Bias Impacts Top-Merited Candidates.
Andersson ER, Hagberg CE, Hägg S
Front Res Metr Anal 2021 ;6():594424

A genome-wide association study of the frailty index highlights brain pathways in ageing.
Atkins JL, Jylhävä J, Pedersen NL, Magnusson PK, Lu Y, Wang Y, Hägg S, Melzer D, Williams DM, Pilling LC
Aging Cell 2021 Sep;20(9):e13459

Frailty trajectories in three longitudinal studies of aging: Is the level or the rate of change more predictive of mortality?
Bai G, Szwajda A, Wang Y, Li X, Bower H, Karlsson IK, Johansson B, Dahl Aslan AK, Pedersen NL, Hägg S, Jylhävä J
Age Ageing 2021 Nov;50(6):2174-2182

Frailty and the risk of dementia: is the association explained by shared environmental and genetic factors?
Bai G, Wang Y, Kuja-Halkola R, Li X, Tomata Y, Karlsson IK, Pedersen NL, Hägg S, Jylhävä J
BMC Med 2021 Oct;19(1):248

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, Pedersen NL, Stringa N, Zettergren A, Hernández I, Montrreal L, Antúnez C, Antonell A, Tankard RM, Bis JC, Sims R, Bellenguez C, Quintela I, González-Perez A, Calero M, Franco-Macías E, Macías J, Blesa R, Cervera-Carles L, Menéndez-González M, Frank-García A, Royo JL, Moreno F, Huerto Vilas R, Baquero M, Diez-Fairen M, Lage C, García-Madrona S, García-González P, Alarcón-Martín E, Valero S, Sotolongo-Grau O, Ullgren A, Naj AC, Lemstra AW, Benaque A, Pérez-Cordón A, Benussi A, Rábano A, Padovani A, Squassina A, de Mendonça A, Arias Pastor A, Kok AAL, Meggy A, Pastor AB, Espinosa A, Corma-Gómez A, Martín Montes A, Sanabria Á, DeStefano AL, Schneider A, Haapasalo A, Kinhult Ståhlbom A, Tybjærg-Hansen A, Hartmann AM, Spottke A, Corbatón-Anchuelo A, Rongve A, Borroni B, Arosio B, Nacmias B, Nordestgaard BG, Kunkle BW, Charbonnier C, Abdelnour C, Masullo C, Martínez Rodríguez C, Muñoz-Fernandez C, Dufouil C, Graff C, Ferreira CB, Chillotti C, Reynolds CA, Fenoglio C, Van Broeckhoven C, Clark C, Pisanu C, Satizabal CL, Holmes C, Buiza-Rueda D, Aarsland D, Rujescu D, Alcolea D, Galimberti D, Wallon D, Seripa D, Grünblatt E, Dardiotis E, Düzel E, Scarpini E, Conti E, Rubino E, Gelpi E, Rodriguez-Rodriguez E, Duron E, Boerwinkle E, Ferri E, Tagliavini F, Küçükali F, Pasquier F, Sanchez-Garcia F, Mangialasche F, Jessen F, Nicolas G, Selbæk G, Ortega G, Chêne G, Hadjigeorgiou G, Rossi G, Spalletta G, Giaccone G, Grande G, Binetti G, Papenberg G, Hampel H, Bailly H, Zetterberg H, Soininen H, Karlsson IK, Alvarez I, Appollonio I, Giegling I, Skoog I, Saltvedt I, Rainero I, Rosas Allende I, Hort J, Diehl-Schmid J, Van Dongen J, Vidal JS, Lehtisalo J, Wiltfang J, Thomassen JQ, Kornhuber J, Haines JL, Vogelgsang J, Pineda JA, Fortea J, Popp J, Deckert J, Buerger K, Morgan K, Fließbach K, Sleegers K, Molina-Porcel L, Kilander L, Weinhold L, Farrer LA, Wang LS, Kleineidam L, Farotti L, Parnetti L, Tremolizzo L, Hausner L, Benussi L, Froelich L, Ikram MA, Deniz-Naranjo MC, Tsolaki M, Rosende-Roca M, Löwenmark M, Hulsman M, Spallazzi M, Pericak-Vance MA, Esiri M, Bernal Sánchez-Arjona M, Dalmasso MC, Martínez-Larrad MT, Arcaro M, Nöthen MM, Fernández-Fuertes M, Dichgans M, Ingelsson M, Herrmann MJ, Scherer M, Vyhnalek M, Kosmidis MH, Yannakoulia M, Schmid M, Ewers M, Heneka MT, Wagner M, Scamosci M, Kivipelto M, Hiltunen M, Zulaica M, Alegret M, Fornage M, Roberto N, van Schoor NM, Seidu NM, Banaj N, Armstrong NJ, Scarmeas N, Scherbaum N, Goldhardt O, Hanon O, Peters O, Skrobot OA, Quenez O, Lerch O, Bossù P, Caffarra P, Dionigi Rossi P, Sakka P, Hoffmann P, Holmans PA, Fischer P, Riederer P, Yang Q, Marshall R, Kalaria RN, Mayeux R, Vandenberghe R, Cecchetti R, Ghidoni R, Frikke-Schmidt R, Sorbi S, Hägg S, Engelborghs S, Helisalmi S, Botne Sando S, Kern S, Archetti S, Boschi S, Fostinelli S, Gil S, Mendoza S, Mead S, Ciccone S, Djurovic S, Heilmann-Heimbach S, Riedel-Heller S, Kuulasmaa T, Del Ser T, Lebouvier T, Polak T, Ngandu T, Grimmer T, Bessi V, Escott-Price V, Giedraitis V, Deramecourt V, Maier W, Jian X, Pijnenburg YAL, , , , , , Kehoe PG, Garcia-Ribas G, Sánchez-Juan P, Pastor P, Pérez-Tur J, Piñol-Ripoll G, Lopez de Munain A, García-Alberca JM, Bullido MJ, Álvarez V, Lleó A, Real LM, Mir P, Medina M, Scheltens P, Holstege H, Marquié M, Sáez ME, Carracedo Á, Amouyel P, Schellenberg GD, Williams J, Seshadri S, van Duijn CM, Mather KA, Sánchez-Valle R, Serrano-Ríos M, Orellana A, Tárraga L, Blennow K, Huisman M, Andreassen OA, Posthuma D, Clarimón J, Boada M, van der Flier WM, Ramirez A, Lambert JC, van der Lee SJ, Ruiz A
Nat Commun 2021 Jun;12(1):3417

Technological readiness and implementation of genomic-driven precision medicine for complex diseases.
Franks PW, Melén E, Friedman M, Sundström J, Kockum I, Klareskog L, Almqvist C, Bergen SE, Czene K, Hägg S, Hall P, Johnell K, Malarstig A, Catrina A, Hagström H, Benson M, Gustav Smith J, Gomez MF, Orho-Melander M, Jacobsson B, Halfvarson J, Repsilber D, Oresic M, Jern C, Melin B, Ohlsson C, Fall T, Rönnblom L, Wadelius M, Nordmark G, Johansson Å, Rosenquist R, Sullivan PF
J Intern Med 2021 Sep;290(3):602-620

Sex differences in biological aging with a focus on human studies.
Hägg S, Jylhävä J
Elife 2021 May;10():

Correction to: Deciphering the genetic and epidemiological landscape of mitochondrial DNA abundance.
Hägg S, Jylhävä J, Wang Y, Czene K, Grassmann F
Hum Genet 2021 Jun;140(6):863

Deciphering the genetic and epidemiological landscape of mitochondrial DNA abundance.
Hägg S, Jylhävä J, Wang Y, Czene K, Grassmann F
Hum Genet 2021 Jun;140(6):849-861

Body mass index and Mini Nutritional Assessment-Short Form as predictors of in-geriatric hospital mortality in older adults with COVID-19.
Kananen L, Eriksdotter M, Boström AM, Kivipelto M, Annetorp M, Metzner C, Bäck Jerlardtz V, Engström M, Johnson P, Lundberg LG, Åkesson E, Sühl Öberg C, Hägg S, Religa D, Jylhävä J, Cederholm T
Clin Nutr 2021 Jul;41(12):2973-9

Epigenome-wide association study of level and change in cognitive abilities from midlife through late life.
Karlsson IK, Ericsson M, Wang Y, Jylhävä J, Hägg S, Dahl Aslan AK, Reynolds CA, Pedersen NL
Clin Epigenetics 2021 Apr;13(1):85

Clinical biomarkers and associations with healthspan and lifespan: Evidence from observational and genetic data.
Li X, Ploner A, Wang Y, Zhan Y, Pedersen NL, Magnusson PK, Jylhävä J, Hägg S
EBioMedicine 2021 Apr;66():103318

Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study.
Lu M, Xueying Q, Hexiang P, Wenjing G, Hägg S, Weihua C, Chunxiao L, Canqing Y, Jun L, Zengchang P, Liming C, Hua W, Xianping W, Yunzhang W, Liming L
Epigenomics 2021 Jun;13(12):939-951

Frailty and comorbidity in predicting community COVID-19 mortality in the U.K. Biobank: The effect of sampling.
Mak JKL, Kuja-Halkola R, Wang Y, Hägg S, Jylhävä J
J Am Geriatr Soc 2021 May;69(5):1128-1139

Sex differences in genetic and environmental influences on frailty and its relation to body mass index and education.
Mak JKL, Reynolds CA, Hägg S, Li X, Ericsson M, Pedersen NL, Jylhävä J, Kuja-Halkola R
Aging (Albany NY) 2021 Jul;13(13):16990-17023

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.
McCartney DL, Min JL, Richmond RC, Lu AT, Sobczyk MK, Davies G, Broer L, Guo X, Jeong A, Jung J, Kasela S, Katrinli S, Kuo PL, Matias-Garcia PR, Mishra PP, Nygaard M, Palviainen T, Patki A, Raffield LM, Ratliff SM, Richardson TG, Robinson O, Soerensen M, Sun D, Tsai PC, van der Zee MD, Walker RM, Wang X, Wang Y, Xia R, Xu Z, Yao J, Zhao W, Correa A, Boerwinkle E, Dugué PA, Durda P, Elliott HR, Gieger C, , de Geus EJC, Harris SE, Hemani G, Imboden M, Kähönen M, Kardia SLR, Kresovich JK, Li S, Lunetta KL, Mangino M, Mason D, McIntosh AM, Mengel-From J, Moore AZ, Murabito JM, , Ollikainen M, Pankow JS, Pedersen NL, Peters A, Polidoro S, Porteous DJ, Raitakari O, Rich SS, Sandler DP, Sillanpää E, Smith AK, Southey MC, Strauch K, Tiwari H, Tanaka T, Tillin T, Uitterlinden AG, Van Den Berg DJ, van Dongen J, Wilson JG, Wright J, Yet I, Arnett D, Bandinelli S, Bell JT, Binder AM, Boomsma DI, Chen W, Christensen K, Conneely KN, Elliott P, Ferrucci L, Fornage M, Hägg S, Hayward C, Irvin M, Kaprio J, Lawlor DA, Lehtimäki T, Lohoff FW, Milani L, Milne RL, Probst-Hensch N, Reiner AP, Ritz B, Rotter JI, Smith JA, Taylor JA, van Meurs JBJ, Vineis P, Waldenberger M, Deary IJ, Relton CL, Horvath S, Marioni RE
Genome Biol 2021 Jun;22(1):194

A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project.
Pirazzini C, Azevedo T, Baldelli L, Bartoletti-Stella A, Calandra-Buonaura G, Dal Molin A, Dimitri GM, Doykov I, Gómez-Garre P, Hägg S, Hällqvist J, Halsband C, Heywood W, Jesús S, Jylhävä J, Kwiatkowska KM, Labrador-Espinosa MA, Licari C, Maturo MG, Mengozzi G, Meoni G, Milazzo M, Periñán-Tocino MT, Ravaioli F, Sala C, Sambati L, Schade S, Schreglmann S, Spasov S, Tenori L, Williams D, Xumerle L, Zago E, Bhatia KP, Capellari S, Cortelli P, Garagnani P, Houlden H, Liò P, Luchinat C, Delledonne M, Mills K, Mir P, Mollenhauer B, Nardini C, Pedersen NL, Provini F, Strom S, Trenkwalder C, Turano P, Bacalini MG, Franceschi C,
Mech Ageing Dev 2021 Mar;194():111426

The epigenetic etiology of cardiovascular disease in a longitudinal Swedish twin study.
Qin X, Karlsson IK, Wang Y, Li X, Pedersen N, Reynolds CA, Hägg S
Clin Epigenetics 2021 Jun;13(1):129

Fatty Acids and Frailty: A Mendelian Randomization Study.
Tomata Y, Wang Y, Hägg S, Jylhävä J
Nutrients 2021 Oct;13(10):

DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.
van Dongen J, Hagenbeek FA, Suderman M, Roetman PJ, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty JD, Adams MJ, Walker RM, Morris SW, Lahti J, Küpers LK, Escaramis G, Alemany S, Jan Bonder M, Meijer M, Ip HF, Jansen R, Baselmans BML, Parmar P, Lowry E, Streit F, Sirignano L, Send TS, Frank J, Jylhävä J, Wang Y, Mishra PP, Colins OF, Corcoran DL, Poulton R, Mill J, Hannon E, Arseneault L, Korhonen T, Vuoksimaa E, Felix JF, Bakermans-Kranenburg MJ, Campbell A, Czamara D, Binder E, Corpeleijn E, Gonzalez JR, Grazuleviciene R, Gutzkow KB, Evandt J, Vafeiadi M, Klein M, van der Meer D, Ligthart L, , Kluft C, Davies GE, Hakulinen C, Keltikangas-Järvinen L, Franke B, Freitag CM, Konrad K, Hervas A, Fernández-Rivas A, Vetro A, Raitakari O, Lehtimäki T, Vermeiren R, Strandberg T, Räikkönen K, Snieder H, Witt SH, Deuschle M, Pedersen NL, Hägg S, Sunyer J, Franke L, Kaprio J, Ollikainen M, Moffitt TE, Tiemeier H, van IJzendoorn MH, Relton C, Vrijheid M, Sebert S, Jarvelin MR, Caspi A, Evans KL, McIntosh AM, Bartels M, Boomsma DI
Mol Psychiatry 2021 Jun;26(6):2148-2162

Comparison of two different frailty scales in the longitudinal Swedish Adoption/Twin Study of Aging (SATSA).
Wennberg AM, Yin W, Fang F, Pedersen NL, Hägg S, Jylhävä J, Modig K
Scand J Public Health 2021 Dec;():14034948211059958

Association between genetically predicted telomere length and facial skin aging in the UK Biobank: a Mendelian randomization study.
Zhan Y, Hägg S
Geroscience 2021 Jun;43(3):1519-1525

Marital status, telomere length and cardiovascular disease risk in a Swedish prospective cohort.
Chen R, Zhan Y, Pedersen N, Fall K, Valdimarsdóttir UA, Hägg S, Fang F
Heart 2020 Feb;106(4):267-272

The Association of Individual Changes in Stressful Life Events and Telomere Length Over Time in Twins 50 Years and Older.
Gerritsen L, Hägg S, Reynolds CA, Pedersen NL
Psychosom Med 2020 ;82(6):614-622

Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality.
Hong MG, Dodig-Crnković T, Chen X, Drobin K, Lee W, Wang Y, Edfors F, Kotol D, Thomas CE, Sjöberg R, Odeberg J, Hamsten A, Silveira A, Hall P, Nilsson P, Pawitan Y, Uhlén M, Pedersen NL, Hägg S, Magnusson PK, Schwenk JM
Life Sci Alliance 2020 Oct;3(10):

Should we invest in biological age predictors to treat colorectal cancer in older adults?
Hägg S, Jylhävä J
Eur J Surg Oncol 2020 Mar;46(3):316-320

Age, Frailty, and Comorbidity as Prognostic Factors for Short-Term Outcomes in Patients With Coronavirus Disease 2019 in Geriatric Care.
Hägg S, Jylhävä J, Wang Y, Xu H, Metzner C, Annetorp M, Garcia-Ptacek S, Khedri M, Boström AM, Kadir A, Johansson A, Kivipelto M, Eriksdotter M, Cederholm T, Religa D
J Am Med Dir Assoc 2020 Nov;21(11):1555-1559.e2

Author Correction: Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.
Jansen IE, Savage JE, Watanabe K, Bryois J, Williams DM, Steinberg S, Sealock J, Karlsson IK, Hägg S, Athanasiu L, Voyle N, Proitsi P, Witoelar A, Stringer S, Aarsland D, Almdahl IS, Andersen F, Bergh S, Bettella F, Bjornsson S, Brækhus A, Bråthen G, de Leeuw C, Desikan RS, Djurovic S, Dumitrescu L, Fladby T, Hohman TJ, Jonsson PV, Kiddle SJ, Rongve A, Saltvedt I, Sando SB, Selbæk G, Shoai M, Skene NG, Snaedal J, Stordal E, Ulstein ID, Wang Y, White LR, Hardy J, Hjerling-Leffler J, Sullivan PF, van der Flier WM, Dobson R, Davis LK, Stefansson H, Stefansson K, Pedersen NL, Ripke S, Andreassen OA, Posthuma D
Nat Genet 2020 Mar;52(3):354

Replicating associations between DNA methylation and body mass index in a longitudinal sample of older twins.
Karlsson IK, Ericsson M, Wang Y, Jylhävä J, Hägg S, Pedersen NL, Reynolds CA, Dahl Aslan AK
Int J Obes (Lond) 2020 Jun;44(6):1397-1405

Childhood Adoption and Mental Health in Adulthood: The Role of Gene-Environment Correlations and Interactions in the UK Biobank.
Lehto K, Hägg S, Lu D, Karlsson R, Pedersen NL, Mosing MA
Biol Psychiatry 2020 Apr;87(8):708-716

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.
Li C, Stoma S, Lotta LA, Warner S, Albrecht E, Allione A, Arp PP, Broer L, Buxton JL, Da Silva Couto Alves A, Deelen J, Fedko IO, Gordon SD, Jiang T, Karlsson R, Kerrison N, Loe TK, Mangino M, Milaneschi Y, Miraglio B, Pervjakova N, Russo A, Surakka I, van der Spek A, Verhoeven JE, Amin N, Beekman M, Blakemore AI, Canzian F, Hamby SE, Hottenga JJ, Jones PD, Jousilahti P, Mägi R, Medland SE, Montgomery GW, Nyholt DR, Perola M, Pietiläinen KH, Salomaa V, Sillanpää E, Suchiman HE, van Heemst D, Willemsen G, Agudo A, Boeing H, Boomsma DI, Chirlaque MD, Fagherazzi G, Ferrari P, Franks P, Gieger C, Eriksson JG, Gunter M, Hägg S, Hovatta I, Imaz L, Kaprio J, Kaaks R, Key T, Krogh V, Martin NG, Melander O, Metspalu A, Moreno C, Onland-Moret NC, Nilsson P, Ong KK, Overvad K, Palli D, Panico S, Pedersen NL, Penninx BWJH, Quirós JR, Jarvelin MR, Rodríguez-Barranco M, Scott RA, Severi G, Slagboom PE, Spector TD, Tjonneland A, Trichopoulou A, Tumino R, Uitterlinden AG, van der Schouw YT, van Duijn CM, Weiderpass E, Denchi EL, Matullo G, Butterworth AS, Danesh J, Samani NJ, Wareham NJ, Nelson CP, Langenberg C, Codd V
Am J Hum Genet 2020 Mar;106(3):389-404

Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up.
Li X, Ploner A, Wang Y, Magnusson PK, Reynolds C, Finkel D, Pedersen NL, Jylhävä J, Hägg S
Elife 2020 Feb;9():

Drivers of Frailty from Adulthood into Old Age: Results from a 27-Year Longitudinal Population-Based Study in Sweden.
Raymond E, Reynolds CA, Dahl Aslan AK, Finkel D, Ericsson M, Hägg S, Pedersen NL, Jylhävä J
J Gerontol A Biol Sci Med Sci 2020 Sep;75(10):1943-1950

A decade of epigenetic change in aging twins: Genetic and environmental contributions to longitudinal DNA methylation.
Reynolds CA, Tan Q, Munoz E, Jylhävä J, Hjelmborg J, Christiansen L, Hägg S, Pedersen NL
Aging Cell 2020 Aug;19(8):e13197

DNA methylation outlier burden, health, and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936.
Seeboth A, McCartney DL, Wang Y, Hillary RF, Stevenson AJ, Walker RM, Campbell A, Evans KL, McIntosh AM, Hägg S, Deary IJ, Marioni RE
Clin Epigenetics 2020 Mar;12(1):49

Polyunsaturated fatty acids and risk of Alzheimer's disease: a Mendelian randomization study.
Tomata Y, Larsson SC, Hägg S
Eur J Nutr 2020 Jun;59(4):1763-1766

Joint impact of common risk factors on incident dementia: A cohort study of the Swedish Twin Registry.
Tomata Y, Li X, Karlsson IK, Mosing MA, Pedersen NL, Hägg S
J Intern Med 2020 Aug;288(2):234-247

Smoking does not accelerate leucocyte telomere attrition: a meta-analysis of 18 longitudinal cohorts.
Bateson M, Aviv A, Bendix L, Benetos A, Ben-Shlomo Y, Bojesen SE, Cooper C, Cooper R, Deary IJ, Hägg S, Harris SE, Kark JD, Kronenberg F, Kuh D, Labat C, Martin-Ruiz CM, Meyer C, Nordestgaard BG, Penninx BWJH, Pepper GV, Révész D, Said MA, Starr JM, Syddall H, Thomson WM, van der Harst P, Whooley M, von Zglinicki T, Willeit P, Zhan Y, Nettle D
R Soc Open Sci 2019 Jun;6(6):190420

Neuroticism as a Predictor of Frailty in Old Age: A Genetically Informative Approach.
Daníelsdóttir HB, Jylhävä J, Hägg S, Lu Y, Colodro-Conde L, Martin NG, Pedersen NL, Mosing MA, Lehto K
Psychosom Med 2019 ;81(9):799-807

Developments in molecular epidemiology of aging.
Hägg S, Belsky DW, Cohen AA
Emerg Top Life Sci 2019 Aug;3(4):411-421

Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.
Jansen IE, Savage JE, Watanabe K, Bryois J, Williams DM, Steinberg S, Sealock J, Karlsson IK, Hägg S, Athanasiu L, Voyle N, Proitsi P, Witoelar A, Stringer S, Aarsland D, Almdahl IS, Andersen F, Bergh S, Bettella F, Bjornsson S, Brækhus A, Bråthen G, de Leeuw C, Desikan RS, Djurovic S, Dumitrescu L, Fladby T, Hohman TJ, Jonsson PV, Kiddle SJ, Rongve A, Saltvedt I, Sando SB, Selbæk G, Shoai M, Skene NG, Snaedal J, Stordal E, Ulstein ID, Wang Y, White LR, Hardy J, Hjerling-Leffler J, Sullivan PF, van der Flier WM, Dobson R, Davis LK, Stefansson H, Stefansson K, Pedersen NL, Ripke S, Andreassen OA, Posthuma D
Nat Genet 2019 Mar;51(3):404-413

Longitudinal changes in the genetic and environmental influences on the epigenetic clocks across old age: Evidence from two twin cohorts.
Jylhävä J, Hjelmborg J, Soerensen M, Munoz E, Tan Q, Kuja-Halkola R, Mengel-From J, Christensen K, Christiansen L, Hägg S, Pedersen NL, Reynolds CA
EBioMedicine 2019 Feb;40():710-716

The frailty index is a predictor of cause-specific mortality independent of familial effects from midlife onwards: a large cohort study.
Li X, Ploner A, Karlsson IK, Liu X, Magnusson PKE, Pedersen NL, Hägg S, Jylhävä J
BMC Med 2019 May;17(1):94

Short-term and long-term case-fatality rates for myocardial infarction and ischaemic stroke by socioeconomic position and sex: a population-based cohort study in Sweden, 1990-1994 and 2005-2009.
Malki N, Hägg S, Tiikkaja S, Koupil I, Sparén P, Ploner A
BMJ Open 2019 Jul;9(7):e026192

Tracking the Epigenetic Clock Across the Human Life Course: A Meta-analysis of Longitudinal Cohort Data.
Marioni RE, Suderman M, Chen BH, Horvath S, Bandinelli S, Morris T, Beck S, Ferrucci L, Pedersen NL, Relton CL, Deary IJ, Hägg S
J Gerontol A Biol Sci Med Sci 2019 Jan;74(1):57-61

Human aging DNA methylation signatures are conserved but accelerated in cultured fibroblasts.
Sturm G, Cardenas A, Bind MA, Horvath S, Wang S, Wang Y, Hägg S, Hirano M, Picard M
Epigenetics 2019 Oct;14(10):961-976

Genetically-predicted life-long lowering of low-density lipoprotein cholesterol is associated with decreased frailty: A Mendelian randomization study in UK biobank.
Wang Q, Wang Y, Lehto K, Pedersen NL, Williams DM, Hägg S
EBioMedicine 2019 Jul;45():487-494

Comprehensive longitudinal study of epigenetic mutations in aging.
Wang Y, Karlsson R, Jylhävä J, Hedman ÅK, Almqvist C, Karlsson IK, Pedersen NL, Almgren M, Hägg S
Clin Epigenetics 2019 Dec;11(1):187

Telomere length and cardiovascular disease risk.
Zhan Y, Hägg S
Curr Opin Cardiol 2019 May;34(3):270-274

Circulating antioxidants and Alzheimer disease prevention: a Mendelian randomization study.
Williams DM, Hägg S, Pedersen NL
Am. J. Clin. Nutr. 2019 Jan;109(1):90-98

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.
Franceschini N, Giambartolomei C, de Vries PS, Finan C, Bis JC, Huntley RP, et al
Nat Commun 2018 12;9(1):5141

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.
Franceschini N, Giambartolomei C, de Vries PS, Finan C, Bis JC, Huntley RP, et al
Nat Commun 2018 12;9(1):5141

Positive bias for European men in peer reviewed applications for faculty position at Karolinska Institutet.
Holst S, Hägg S
F1000Res ;6():2145

A Frailty Index for UK Biobank Participants.
Williams DM, Jylhävä J, Pedersen NL, Hägg S
J. Gerontol. A Biol. Sci. Med. Sci. 2019 Mar;74(4):582-587

A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia.
Chen X, Gustafsson S, Whitington T, Borné Y, Lorentzen E, Sun J, et al
Hum. Mol. Genet. 2018 05;27(10):1809-1818

Apolipoprotein E DNA methylation and late-life disease.
Karlsson IK, Ploner A, Wang Y, Gatz M, Pedersen NL, Hägg S
Int J Epidemiol 2018 Mar;():

Association of telomere length with general cognitive trajectories: a meta-analysis of four prospective cohort studies.
Zhan Y, Clements MS, Roberts RO, Vassilaki M, Druliner BR, Boardman LA, et al
Neurobiol. Aging 2018 09;69():111-116

Circulating insulin-like growth factors and Alzheimer disease: A mendelian randomization study.
Williams DM, Karlsson IK, Pedersen NL, Hägg S
Neurology 2018 01;90(4):e291-e297

DNA Methylation and All-Cause Mortality in Middle-Aged and Elderly Danish Twins.
Svane AM, Soerensen M, Lund J, Tan Q, Jylhävä J, Wang Y, et al
Genes (Basel) 2018 Feb;9(2):

Genetic and Environmental Contributions to the Covariation Between Cardiometabolic Traits.
Chen X, Kuja-Halkola R, Chang Z, Karlsson R, Hägg S, Svensson P, et al
J Am Heart Assoc 2018 Apr;7(9):

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.
Savage JE, Jansen PR, Stringer S, Watanabe K, Bryois J, de Leeuw CA, et al
Nat. Genet. 2018 07;50(7):912-919

Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants.
Zhou A, Taylor AE, Karhunen V, Zhan Y, Rovio SP, Lahti J, et al
Sci Rep 2018 May;8(1):7526

Leukocyte Telomere Length and All-Cause Mortality: A Between-Within Twin Study With Time-Dependent Effects Using Generalized Survival Models.
Zhan Y, Liu XR, Reynolds CA, Pedersen NL, Hägg S, Clements MS
Am. J. Epidemiol. 2018 Oct;187(10):2186-2191

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.
Davies G, Lam M, Harris SE, Trampush JW, Luciano M, Hill WD, et al
Nat Commun 2018 05;9(1):2098

Tracking the Epigenetic Clock Across the Human Life Course: A Meta-analysis of Longitudinal Cohort Data.
Marioni RE, Suderman M, Chen BH, Horvath S, Bandinelli S, Morris T, et al
J. Gerontol. A Biol. Sci. Med. Sci. 2019 Jan;74(1):57-61

An epigenome-wide association study meta-analysis of educational attainment.
Karlsson Linnér R, Marioni RE, Rietveld CA, Simpkin AJ, Davies NM, Watanabe K, et al
Mol. Psychiatry 2017 Dec;22(12):1680-1690

Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study.
Zhan Y, Karlsson IK, Karlsson R, Tillander A, Reynolds CA, Pedersen NL, et al
Circ. Res. 2017 Jul;121(3):214-219

Frailty index as a predictor of all-cause and cause-specific mortality in a Swedish population-based cohort.
Jiang M, Foebel AD, Kuja-Halkola R, Karlsson I, Pedersen NL, Hägg S, et al
Aging (Albany NY) 2017 12;9(12):2629-2646

Genetic susceptibility to cardiovascular disease and risk of dementia.
Karlsson IK, Ploner A, Song C, Gatz M, Pedersen NL, Hägg S
Transl Psychiatry 2017 05;7(5):e1142

Short telomere length is associated with impaired cognitive performance in European ancestry cohorts.
Hägg S, Zhan Y, Karlsson R, Gerritsen L, Ploner A, van der Lee SJ, et al
Transl Psychiatry 2017 04;7(4):e1100

Vitamin D and cognitive function: A Mendelian randomisation study.
Maddock J, Zhou A, Cavadino A, Kuźma E, Bao Y, Smart MC, et al
Sci Rep 2017 10;7(1):13230

Ganna A, Fall T, Salihovic S, Lee W, Broeckling CD, Kumar J, Hagg S, Stenemo M, Magnusson PKE, Prenni JE, Lind L, Pawitan Y, Ingelsson E. Large-scale non-targeted metabolomic profiling in three human population-based studies. Metabolomics 2016 12;1. https://doi.org/10.1007/s11306-015-0893-5

Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk.
Berglund K, Reynolds CA, Ploner A, Gerritsen L, Hovatta I, Pedersen NL, et al
Aging (Albany NY) 2016 07;8(7):1398-415

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.
Hägg S, Fall T, Ploner A, Mägi R, Fischer K, Draisma HH, et al
Int J Epidemiol 2015 Apr;44(2):578-86

Age- and sex-specific causal effects of adiposity on cardiovascular risk factors.
Fall T, Hägg S, Ploner A, Mägi R, Fischer K, Draisma HH, et al
Diabetes 2015 May;64(5):1841-52

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.
Horikoshi M, Mӓgi R, van de Bunt M, Surakka I, Sarin AP, Mahajan A, et al
PLoS Genet. 2015 Jul;11(7):e1005230

Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models.
Chen X, Kuja-Halkola R, Rahman I, Arpegård J, Viktorin A, Karlsson R, et al
Am. J. Hum. Genet. 2015 Nov;97(5):708-14

Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity.
Hägg S, Ganna A, Van Der Laan SW, Esko T, Pers TH, Locke AE, et al
Hum. Mol. Genet. 2015 Dec;24(23):6849-60

Telomere Length Shortening and Alzheimer Disease--A Mendelian Randomization Study.
Zhan Y, Song C, Karlsson R, Tillander A, Reynolds CA, Pedersen NL, et al
JAMA Neurol 2015 Oct;72(10):1202-3

The impact of low-frequency and rare variants on lipid levels.
Surakka I, Horikoshi M, Mägi R, Sarin AP, Mahajan A, Lagou V, et al
Nat. Genet. 2015 Jun;47(6):589-97

DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.
Perry JR, Hsu YH, Chasman DI, Johnson AD, Elks C, Albrecht E, et al
Hum. Mol. Genet. 2014 May;23(9):2490-7

Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break.
Lindgren E, Hägg S, Giordano F, Björkegren J, Ström L
Cell Cycle 2014 ;13(23):3645-58

Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers.
Deelen J, Beekman M, Codd V, Trompet S, Broer L, Hägg S, et al
Int J Epidemiol 2014 Jun;43(3):878-86

Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis.
Björkegren JL, Hägg S, Talukdar HA, Foroughi Asl H, Jain RK, Cedergren C, et al
PLoS Genet. 2014 Feb;10(2):e1004201

Serum selenium in relation to measures of glucose metabolism and incidence of Type 2 diabetes in an older Swedish population.
Gao H, Hägg S, Sjögren P, Lambert PC, Ingelsson E, van Dam RM
Diabet. Med. 2014 Jul;31(7):787-93

Telomere length in circulating leukocytes is associated with lung function and disease.
Albrecht E, Sillanpää E, Karrasch S, Alves AC, Codd V, Hovatta I, et al
Eur. Respir. J. 2014 Apr;43(4):983-92

Evidence of a causal relationship between adiponectin levels and insulin sensitivity: a Mendelian randomization study.
Gao H, Fall T, van Dam RM, Flyvbjerg A, Zethelius B, Ingelsson E, et al
Diabetes 2013 Apr;62(4):1338-44

GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.
Rietveld CA, Medland SE, Derringer J, Yang J, Esko T, Martin NW, et al
Science 2013 Jun;340(6139):1467-71

Identification of seven loci affecting mean telomere length and their association with disease.
Codd V, Nelson CP, Albrecht E, Mangino M, Deelen J, Buxton JL, et al
Nat. Genet. 2013 Apr;45(4):422-7, 427e1-2

The role of adiposity in cardiometabolic traits: a Mendelian randomization analysis.
Fall T, Hägg S, Mägi R, Ploner A, Fischer K, Horikoshi M, et al
PLoS Med. 2013 ;10(6):e1001474

Variation in genes in the endothelin pathway and endothelium-dependent and endothelium-independent vasodilation in an elderly population.
Lind L, Syvänen AC, Axelsson T, Lundmark P, Hägg S, Larsson A
Acta Physiol (Oxf) 2013 May;208(1):88-94

Relative deprivation and mortality--a longitudinal study in a Swedish population of 4.7 million, 1990-2006.
Åberg Yngwe M, Kondo N, Hägg S, Kawachi I
BMC Public Health 2012 Aug;12():664

Blood levels of dual-specificity phosphatase-1 independently predict risk for post-operative morbidities causing prolonged hospitalization after coronary artery bypass grafting.
Hägg S, Alserius T, Noori P, Ruusalepp A, Ivert T, Tegnér J, et al
Int. J. Mol. Med. 2011 Jun;27(6):851-7

Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.
Hägg S, Salehpour M, Noori P, Lundström J, Possnert G, Takolander R, et al
PLoS ONE 2011 Apr;6(4):e18248

Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study.
Hägg S, Skogsberg J, Lundström J, Noori P, Nilsson R, Zhong H, et al
PLoS Genet. 2009 Dec;5(12):e1000754

Biological Age Predictors.
Jylhävä J, Pedersen NL, Hägg S
EBioMedicine 2017 Jul;21():29-36

Telomere Length Shortening in Alzheimer's Disease: Procedures for a Causal Investigation Using Single Nucleotide Polymorphisms in a Mendelian Randomization Study.
Zhan Y, Hägg S
Methods Mol. Biol. 2018 ;1750():293-306

Telomere Length Dynamics and Atherosclerotic Disease.
Hägg S
Circ. Res. 2018 Feb;122(4):546-547