331 results on '"Lu, Ake T."'
Search Results
2. Fundamental equations linking methylation dynamics to maximum lifespan in mammals
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Horvath, Steve, Zhang, Joshua, Haghani, Amin, Lu, Ake T., and Fei, Zhe
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- 2024
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3. Causality-enriched epigenetic age uncouples damage and adaptation
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Ying, Kejun, Liu, Hanna, Tarkhov, Andrei E., Sadler, Marie C., Lu, Ake T., Moqri, Mahdi, Horvath, Steve, Kutalik, Zoltán, Shen, Xia, and Gladyshev, Vadim N.
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- 2024
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4. Higher testosterone and testosterone/estradiol ratio in men are associated with decreased Pheno-/GrimAge and DNA-methylation based PAI1
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Kusters, Cynthia D. J., Paul, Kimberly C., Lu, Ake T., Ferruci, Luigi, Ritz, Beate R., Binder, Alexandra M., and Horvath, Steve
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- 2024
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5. DNA methylation clocks for clawed frogs reveal evolutionary conservation of epigenetic aging
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Zoller, Joseph A., Parasyraki, Eleftheria, Lu, Ake T., Haghani, Amin, Niehrs, Christof, and Horvath, Steve
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- 2024
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6. Centenarian clocks: epigenetic clocks for validating claims of exceptional longevity
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Dec, Eric, Clement, James, Cheng, Kaiyang, Church, George M, Fossel, Michael B, Rehkopf, David H, Rosero-Bixby, Luis, Kobor, Michael S, Lin, David TS, Lu, Ake T, Fei, Zhe, Guo, Wei, Chew, Yap Ching, Yang, Xiaojing, Putra, Sulistyo E Dwi, Reiner, Alex P, Correa, Adolfo, Vilalta, Adrian, Pirazzini, Chiara, Passarino, Giuseppe, Monti, Daniela, Arosio, Beatrice, Garagnani, Paolo, Franceschi, Claudio, and Horvath, Steve
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Biological Sciences ,Genetics ,Aging ,Clinical Research ,Human Genome ,Aged ,80 and over ,Humans ,Longevity ,Centenarians ,DNA Methylation ,Epigenesis ,Genetic ,Centenarian clocks ,Epigenetic clocks ,Clinical sciences - Abstract
Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.
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- 2023
7. Alcohol consumption and epigenetic age acceleration in young adults
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Nannini, Drew R, Joyce, Brian T, Zheng, Yinan, Gao, Tao, Wang, Jun, Liu, Lei, Jacobs, David R, Schreiner, Pamela J, Liu, Chunyu, Dai, Qi, Horvath, Steve, Lu, Ake T, Yaffe, Kristine, Greenland, Philip, Lloyd-Jones, Donald M, and Hou, Lifang
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Pediatric ,Clinical Research ,Genetics ,Underage Drinking ,Alcoholism ,Alcohol Use and Health ,Aging ,Substance Misuse ,2.3 Psychological ,social and economic factors ,Aetiology ,Oral and gastrointestinal ,Cardiovascular ,Stroke ,Cancer ,Good Health and Well Being ,Aged ,Humans ,Alcohol Drinking ,Alcoholic Beverages ,Beer ,Binge Drinking ,United States ,Wine ,Epigenomics ,alcohol ,epigenetic age ,DNA methylation ,lifetime alcohol consumption ,binge drinking ,Biochemistry and Cell Biology ,Physiology ,Oncology and Carcinogenesis ,Developmental Biology - Abstract
Alcohol is a widely consumed substance in the United States, however its effect on aging remains understudied. In this study of young adults, we examined whether cumulative alcohol consumption, i.e., alcohol years of beer, liquor, wine, and total alcohol, and recent binge drinking, were associated with four measures of age-related epigenetic changes via blood DNA methylation. A random subset of study participants in the Coronary Artery Risk Development in Young Adults Study underwent DNA methylation profiling using the Illumina MethylationEPIC Beadchip. Participants with alcohol consumption and methylation data at examination years 15 (n = 1,030) and 20 (n = 945) were included. Liquor and total alcohol consumption were associated with a 0.31-year (P = 0.002) and a 0.12-year (P = 0.013) greater GrimAge acceleration (GAA) per additional five alcohol years, while beer and wine consumption observed marginal (P = 0.075) and no associations (P = 0.359) with GAA, respectively. Any recent binge drinking and the number of days of binge drinking were associated with a 1.38-year (P < 0.001) and a 0.15-year (P < 0.001) higher GAA, respectively. We observed statistical interactions between cumulative beer (P < 0.001) and total alcohol (P = 0.004) consumption with chronological age, with younger participants exhibiting a higher average in GAA compared to older participants. No associations were observed with the other measures of epigenetic aging. These results suggest cumulative liquor and total alcohol consumption and recent binge drinking may alter age-related epigenetic changes as captured by GAA. With the increasing aging population and widespread consumption of alcohol, these findings may have potential implications for lifestyle modification to promote healthy aging.
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- 2023
8. Correction to: Higher testosterone and testosterone/estradiol ratio in men are associated with decreased Pheno‑/GrimAge and DNA‑methylation based PAI1
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Kusters, Cynthia D. J., Paul, Kimberly C., Lu, Ake T., Ferrucci, Luigi, Ritz, Beate R., Binder, Alexandra M., and Horvath, Steve
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- 2024
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9. Pan-primate studies of age and sex
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Horvath, Steve, Haghani, Amin, Zoller, Joseph A., Lu, Ake T., Ernst, Jason, Pellegrini, Matteo, Jasinska, Anna J., Mattison, Julie A., Salmon, Adam B., Raj, Ken, Horvath, Markus, Paul, Kimberly C., Ritz, Beate R., Robeck, Todd R., Spriggs, Maria, Ehmke, Erin E., Jenkins, Susan, Li, Cun, and Nathanielsz, Peter W.
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- 2023
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10. DNA methylation GrimAge version 2
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Lu, Ake T, Binder, Alexandra M, Zhang, Joshua, Yan, Qi, Reiner, Alex P, Cox, Simon R, Corley, Janie, Harris, Sarah E, Kuo, Pei-Lun, Moore, Ann Z, Bandinelli, Stefania, Stewart, James D, Wang, Cuicui, Hamlat, Elissa J, Epel, Elissa S, Schwartz, Joel D, Whitsel, Eric A, Correa, Adolfo, Ferrucci, Luigi, Marioni, Riccardo E, and Horvath, Steve
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Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Good Health and Well Being ,Humans ,Aged ,Aged ,80 and over ,DNA Methylation ,Aging ,Diabetes Mellitus ,Type 2 ,Metabolic Syndrome ,Biomarkers ,Epigenesis ,Genetic ,DNA methylation ,epigenetic clock ,mortality ,healthspan ,Biochemistry and cell biology ,Clinical sciences - Abstract
We previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. Here we describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C). We evaluate GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6x10-167 versus P=2.6x10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1x10-136), computed tomography based measurements of fatty liver disease. We present evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome. DNAm logCRP is positively correlated with morbidity count (P=1.3x10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8x10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6x10-267) and visceral fat (cor=0.41, P=4.7x10-41). Overall, we demonstrate that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk.
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- 2022
11. Marijuana use and DNA methylation-based biological age in young adults
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Nannini, Drew R, Zheng, Yinan, Joyce, Brian T, Gao, Tao, Liu, Lei, Jacobs, David R, Schreiner, Pamela, Liu, Chunyu, Horvath, Steve, Lu, Ake T, Yaffe, Kristine, Sidney, Stephen, Greenland, Philip, Lloyd-Jones, Donald M, and Hou, Lifang
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Biological Sciences ,Genetics ,Clinical Research ,Human Genome ,Alcoholism ,Alcohol Use and Health ,Cannabinoid Research ,Aging ,Substance Misuse ,Cancer ,Cardiovascular ,Good Health and Well Being ,Humans ,Young Adult ,DNA Methylation ,Marijuana Use ,Epigenesis ,Genetic ,Epigenomics ,Marijuana ,Epigenetic age acceleration ,Alcohol ,CARDIA ,Clinical Sciences ,Paediatrics and Reproductive Medicine - Abstract
BackgroundMarijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana's effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation.ResultsA random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with available whole blood at examination years (Y) 15 and Y20 underwent epigenomic profiling. Four EAA estimates (intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration, PhenoAge acceleration, and GrimAge acceleration) were calculated from DNA methylation levels measured at Y15 and Y20. Ever use and cumulative marijuana-years were calculated from the baseline visit to Y15 and Y20, and recent marijuana use (both any and number of days of use in the last 30 days) were calculated at Y15 and Y20. Ever use of marijuana and each additional marijuana-year were associated with a 6-month (P
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- 2022
12. Association of subjective social status with epigenetic aging among Black and White women
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Hamlat, Elissa J, Adler, Nancy E, Laraia, Barbara, Surachman, Agus, Lu, Ake T, Zhang, Joshua, Horvath, Steve, and Epel, Elissa S
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Biomedical and Clinical Sciences ,Psychology ,Genetics ,Health Disparities ,Aging ,Clinical Research ,Adult ,Black People ,Child ,Epigenesis ,Genetic ,Female ,Humans ,Social Class ,Social Status ,Socioeconomic status ,Subjective social status ,Epigenetic clock ,Epigenetic age acceleration ,Race ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Biomedical and clinical sciences - Abstract
ObjectiveSubjective social status (SSS), an individual's assessment of their own social status in relation to others, is associated with health and mortality independently of objective SES; however, no studies have tested whether SSS influences epigenetic aging. The current study examines if SSS is associated with epigenetic age acceleration in both Black and White women, independently of objective SES measured during both childhood and adulthood.MethodFor 9- and 10-year-old Black and White girls, parental education and annual household income was obtained. At ages 39-42, 361 participants (175 Black, 186 White) reported their current education, household income, and SSS, and provided saliva to assess age acceleration using the GrimAge epigenetic clock. Linear regression estimated the association of SSS with epigenetic age acceleration, controlling for objective SES (current education, current income, parents' education, income during childhood), smoking, and counts of cell types.ResultsWhen all objective SES variables were included in the model, SSS remained significantly associated with epigenetic age acceleration, b = - 0.31, p = .003, ß = - 0.15. Black women had significantly greater age acceleration than White women, (t(359) = 5.20, p > .001, d = 0.55) but race did not moderate the association between SSS and epigenetic age acceleration.ConclusionsWomen who rated themselves lower in SSS had greater epigenetic age acceleration, regardless of income and education. There was no difference by race for this association.
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- 2022
13. Multi-omic rejuvenation and lifespan extension on exposure to youthful circulation
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Zhang, Bohan, Lee, David E., Trapp, Alexandre, Tyshkovskiy, Alexander, Lu, Ake T., Bareja, Akshay, Kerepesi, Csaba, McKay, Lauren K., Shindyapina, Anastasia V., Dmitriev, Sergey E., Baht, Gurpreet S., Horvath, Steve, Gladyshev, Vadim N., and White, James P.
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- 2023
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14. Refining epigenetic prediction of chronological and biological age
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Bernabeu, Elena, McCartney, Daniel L., Gadd, Danni A., Hillary, Robert F., Lu, Ake T., Murphy, Lee, Wrobel, Nicola, Campbell, Archie, Harris, Sarah E., Liewald, David, Hayward, Caroline, Sudlow, Cathie, Cox, Simon R., Evans, Kathryn L., Horvath, Steve, McIntosh, Andrew M., Robinson, Matthew R., Vallejos, Catalina A., and Marioni, Riccardo E.
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- 2023
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15. A mammalian methylation array for profiling methylation levels at conserved sequences
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Arneson, Adriana, Haghani, Amin, Thompson, Michael J, Pellegrini, Matteo, Kwon, Soo Bin, Vu, Ha, Maciejewski, Emily, Yao, Mingjia, Li, Caesar Z, Lu, Ake T, Morselli, Marco, Rubbi, Liudmilla, Barnes, Bret, Hansen, Kasper D, Zhou, Wanding, Breeze, Charles E, Ernst, Jason, and Horvath, Steve
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Genetics ,Human Genome ,Animals ,Biomarkers ,Conserved Sequence ,CpG Islands ,DNA Methylation ,Epigenesis ,Genetic ,Humans ,Mammals ,Mice ,Mutation ,Protein Processing ,Post-Translational ,Rats ,Transcriptome - Abstract
Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures up to 36k CpGs per species that are well conserved across many mammalian species. We designed a set of probes that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development of epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others.
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- 2022
16. Epigenetic Age and the Risk of Incident Atrial Fibrillation
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Roberts, Jason D, Vittinghoff, Eric, Lu, Ake T, Alonso, Alvaro, Wang, Biqi, Sitlani, Colleen M, Mohammadi-Shemirani, Pedrum, Fornage, Myriam, Kornej, Jelena, Brody, Jennifer A, Arking, Dan E, Lin, Honghuang, Heckbert, Susan R, Prokic, Ivana, Ghanbari, Mohsen, Skanes, Allan C, Bartz, Traci M, Perez, Marco V, Taylor, Kent D, Lubitz, Steven A, Ellinor, Patrick T, Lunetta, Kathryn L, Pankow, James S, Paré, Guillaume, Sotoodehnia, Nona, Benjamin, Emelia J, Horvath, Steve, and Marcus, Gregory M
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Epidemiology ,Health Sciences ,Genetics ,Aging ,Heart Disease ,Clinical Research ,Cardiovascular ,Good Health and Well Being ,Aged ,Atrial Fibrillation ,DNA Methylation ,Epigenesis ,Genetic ,Epigenomics ,Female ,Follow-Up Studies ,Humans ,Incidence ,Male ,Mendelian Randomization Analysis ,Middle Aged ,Models ,Cardiovascular ,Models ,Genetic ,atrial fibrillation ,aging ,genetics ,epigenomics ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences ,Sports science and exercise - Abstract
BackgroundThe most prominent risk factor for atrial fibrillation (AF) is chronological age; however, underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge in a phenomenon referred to as epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF.MethodsMeasures for 4 epigenetic clocks (Horvath, Hannum, DNA methylation [DNAm] PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 (plasminogen activator inhibitor-1) levels (ie, DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analyses. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF.ResultsAmong 5600 participants (mean age, 65.5 years; female, 60.1%; Black, 50.7%), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. After multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five-year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19% (adjusted hazard ratio [HR], 1.19 [95% CI, 1.09-1.31]; P
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- 2021
17. DNA methylation-based surrogates of plasma proteins are associated with Parkinson's disease risk.
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Fu, Katherine A, Paul, Kimberly C, Lu, Ake T, Horvath, Steve, Keener, Adrienne M, Bordelon, Yvette, Bronstein, Jeff M, and Ritz, Beate
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Humans ,Parkinson Disease ,Disease Susceptibility ,Blood Proteins ,Case-Control Studies ,DNA Methylation ,Epigenesis ,Genetic ,Cardiovascular disease ,DNA methylation ,Disease risk ,Epigenetics ,Parkinson's disease ,Neurosciences ,Prevention ,Neurodegenerative ,Parkinson's Disease ,Brain Disorders ,Aging ,Clinical Research ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Neurological ,Good Health and Well Being ,Clinical Sciences ,Psychology - Abstract
BackgroundThe epigenome may reflect Parkinson's disease (PD) risk, which serves as a point of convergence of genetic and environmental risk factors. Here, we investigate whether blood DNA methylation (DNAm) markers are associated with PD risk.MethodsWe selected 12 plasma proteins known as predictors of cardiovascular conditions and mortality to evaluate their effects on PD risk in a case-control study. In lieu of protein level measures, however, we assessed the influence of their DNAm surrogates. Primary analysis was restricted to 569 PD patients and 238 controls with DNAm data available. Using univariate logistic regression, we evaluated associations between the DNAm markers and PD.ResultsOf the 12 DNAm surrogates, the most robustly associated were DNAm EFEMP-1 and DNAm CD56, which were associated with PD with and without controlling for blood cell composition. DNAm EFEMP-1 was associated with a decreased risk of PD (OR = 0.83 per SD, 95% CI = 0.70, 0.98) whereas DNAm CD56 was associated with an increased risk of PD (OR = 1.41, 95% CI = 1.11, 1.79).ConclusionsSeveral DNAm markers, selected as part of a panel to track cardiovascular outcomes and mortality, were associated with PD risk. DNAm markers may inform of factors that are affected differentially in early PD patients compared with controls.
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- 2021
18. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
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McCartney, Daniel L, Min, Josine L, Richmond, Rebecca C, Lu, Ake T, Sobczyk, Maria K, Davies, Gail, Broer, Linda, Guo, Xiuqing, Jeong, Ayoung, Jung, Jeesun, Kasela, Silva, Katrinli, Seyma, Kuo, Pei-Lun, Matias-Garcia, Pamela R, Mishra, Pashupati P, Nygaard, Marianne, Palviainen, Teemu, Patki, Amit, Raffield, Laura M, Ratliff, Scott M, Richardson, Tom G, Robinson, Oliver, Soerensen, Mette, Sun, Dianjianyi, Tsai, Pei-Chien, van der Zee, Matthijs D, Walker, Rosie M, Wang, Xiaochuan, Wang, Yunzhang, Xia, Rui, Xu, Zongli, Yao, Jie, Zhao, Wei, Correa, Adolfo, Boerwinkle, Eric, Dugué, Pierre-Antoine, Durda, Peter, Elliott, Hannah R, Gieger, Christian, de Geus, Eco JC, Harris, Sarah E, Hemani, Gibran, Imboden, Medea, Kähönen, Mika, Kardia, Sharon LR, Kresovich, Jacob K, Li, Shengxu, Lunetta, Kathryn L, Mangino, Massimo, Mason, Dan, McIntosh, Andrew M, Mengel-From, Jonas, Moore, Ann Zenobia, Murabito, Joanne M, Ollikainen, Miina, Pankow, James S, Pedersen, Nancy L, Peters, Annette, Polidoro, Silvia, Porteous, David J, Raitakari, Olli, Rich, Stephen S, Sandler, Dale P, Sillanpää, Elina, Smith, Alicia K, Southey, Melissa C, Strauch, Konstantin, Tiwari, Hemant, Tanaka, Toshiko, Tillin, Therese, Uitterlinden, Andre G, Van Den Berg, David J, van Dongen, Jenny, Wilson, James G, Wright, John, Yet, Idil, Arnett, Donna, Bandinelli, Stefania, Bell, Jordana T, Binder, Alexandra M, Boomsma, Dorret I, Chen, Wei, Christensen, Kaare, Conneely, Karen N, Elliott, Paul, Ferrucci, Luigi, Fornage, Myriam, Hägg, Sara, Hayward, Caroline, Irvin, Marguerite, Kaprio, Jaakko, Lawlor, Deborah A, Lehtimäki, Terho, Lohoff, Falk W, Milani, Lili, Milne, Roger L, Probst-Hensch, Nicole, Reiner, Alex P, Ritz, Beate, and Rotter, Jerome I
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Prevention ,Nutrition ,Aging ,Human Genome ,Genetics ,Generic health relevance ,Inflammatory and immune system ,Good Health and Well Being ,Adiposity ,Biomarkers ,C-Reactive Protein ,CpG Islands ,DNA Methylation ,Educational Status ,Epigenesis ,Genetic ,Genetic Loci ,Genetic Markers ,Genome ,Human ,Genome-Wide Association Study ,Granulocytes ,Humans ,Immunity ,Innate ,Lipid Metabolism ,Multifactorial Inheritance ,Plasminogen Activator Inhibitor 1 ,DNA methylation ,GWAS ,Epigenetic clock ,Genetics of DNA Methylation Consortium ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium ,Environmental Sciences ,Biological Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundBiological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.ResultsLeveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.ConclusionThis study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
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- 2021
19. DNA methylation age analysis of rapamycin in common marmosets
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Horvath, Steve, Zoller, Joseph A, Haghani, Amin, Lu, Ake T, Raj, Ken, Jasinska, Anna J, Mattison, Julie A, and Salmon, Adam B
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Biological Sciences ,Genetics ,Aging ,Animals ,Callithrix ,Chlorocebus aethiops ,DNA Methylation ,Epigenesis ,Genetic ,Macaca mulatta ,Mice ,Sirolimus ,Marmoset ,Development ,Epigenetic clock ,DNA methylation ,Clinical sciences - Abstract
Human DNA methylation data have previously been used to develop highly accurate biomarkers of aging ("epigenetic clocks"). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.
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- 2021
20. Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci.
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Sugrue, Victoria J, Zoller, Joseph Alan, Narayan, Pritika, Lu, Ake T, Ortega-Recalde, Oscar J, Grant, Matthew J, Bawden, C Simon, Rudiger, Skye R, Haghani, Amin, Bond, Donna M, Hore, Reuben R, Garratt, Michael, Sears, Karen E, Wang, Nan, Yang, Xiangdong William, Snell, Russell G, Hore, Timothy A, and Horvath, Steve
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DNA methylation ,aging ,androgens ,castration ,developmental biology ,epigenetic clock ,genetics ,genomics ,human ,mouse ,sheep ,Biochemistry and Cell Biology - Abstract
In mammals, females generally live longer than males. Nevertheless, the mechanisms underpinning sex-dependent longevity are currently unclear. Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age and identifying novel factors influencing the aging rate using only DNA methylation data. In this study, we developed the first epigenetic clock for domesticated sheep (Ovis aries), which can predict chronological age with a median absolute error of 5.1 months. We have discovered that castrated male sheep have a decelerated aging rate compared to intact males, mediated at least in part by the removal of androgens. Furthermore, we identified several androgen-sensitive CpG dinucleotides that become progressively hypomethylated with age in intact males, but remain stable in castrated males and females. Comparable sex-specific methylation differences in MKLN1 also exist in bat skin and a range of mouse tissues that have high androgen receptor expression, indicating that it may drive androgen-dependent hypomethylation in divergent mammalian species. In characterizing these sites, we identify biologically plausible mechanisms explaining how androgens drive male-accelerated aging.
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- 2021
21. Clonal hematopoiesis associated with epigenetic aging and clinical outcomes
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Nachun, Daniel, Lu, Ake T, Bick, Alexander G, Natarajan, Pradeep, Weinstock, Joshua, Szeto, Mindy D, Kathiresan, Sekar, Abecasis, Goncalo, Taylor, Kent D, Guo, Xiuqing, Tracy, Russ, Durda, Peter, Liu, Yongmei, Johnson, Craig, Rich, Stephen S, Van Den Berg, David, Laurie, Cecilia, Blackwell, Tom, Papanicolaou, George J, Correa, Adolfo, Raffield, Laura M, Johnson, Andrew D, Murabito, Joanne, Manson, JoAnn E, Desai, Pinkal, Kooperberg, Charles, Assimes, Themistocles L, Levy, Daniel, Rotter, Jerome I, Reiner, Alex P, Whitsel, Eric A, Wilson, James G, Horvath, Steve, Jaiswal, Siddhartha, and Consortium, the NHLBI Trans‐Omics for Precision Medicine
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Aging ,Heart Disease ,Cardiovascular ,Patient Safety ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Clonal Hematopoiesis ,Epigenomics ,Humans ,Risk Factors ,Treatment Outcome ,clonal hematopoiesis ,epigenomics ,heart disease ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Clonal hematopoiesis of indeterminate potential (CHIP) is a common precursor state for blood cancers that most frequently occurs due to mutations in the DNA-methylation modifying enzymes DNMT3A or TET2. We used DNA-methylation array and whole-genome sequencing data from four cohorts together comprising 5522 persons to study the association between CHIP, epigenetic clocks, and health outcomes. CHIP was strongly associated with epigenetic age acceleration, defined as the residual after regressing epigenetic clock age on chronological age, in several clocks, ranging from 1.31 years (GrimAge, p 0 in both Hannum and GrimAge (referred to as AgeAccelHG+). This group was at high risk of all-cause mortality (hazard ratio 2.90, p
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- 2021
22. Multi-species and multi-tissue methylation clocks for age estimation in toothed whales and dolphins.
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Robeck, Todd R, Fei, Zhe, Lu, Ake T, Haghani, Amin, Jourdain, Eve, Zoller, Joseph A, Li, Caesar Z, Steinman, Karen J, DiRocco, Stacy, Schmitt, Todd, Osborn, Steve, Van Bonn, Bill, Katsumata, Etsuko, Mergl, June, Almunia, Javier, Rodriguez, Magdalena, Haulena, Martin, Dold, Christopher, and Horvath, Steve
- Abstract
The development of a precise blood or skin tissue DNA Epigenetic Aging Clock for Odontocete (OEAC) would solve current age estimation inaccuracies for wild odontocetes. Therefore, we determined genome-wide DNA methylation profiles using a custom array (HorvathMammalMethyl40) across skin and blood samples (n = 446) from known age animals representing nine odontocete species within 4 phylogenetic families to identify age associated CG dinucleotides (CpGs). The top CpGs were used to create a cross-validated OEAC clock which was highly correlated for individuals (r = 0.94) and for unique species (median r = 0.93). Finally, we applied the OEAC for estimating the age and sex of 22 wild Norwegian killer whales. DNA methylation patterns of age associated CpGs are highly conserved across odontocetes. These similarities allowed us to develop an odontocete epigenetic aging clock (OEAC) which can be used for species conservation efforts by provide a mechanism for estimating the age of free ranging odontocetes from either blood or skin samples.
- Published
- 2021
23. Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons
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Reid, Dylan A, Reed, Patrick J, Schlachetzki, Johannes CM, Nitulescu, Ioana I, Chou, Grace, Tsui, Enoch C, Jones, Jeffrey R, Chandran, Sahaana, Lu, Ake T, McClain, Claire A, Ooi, Jean H, Wang, Tzu-Wen, Lana, Addison J, Linker, Sara B, Ricciardulli, Anthony S, Lau, Shong, Schafer, Simon T, Horvath, Steve, Dixon, Jesse R, Hah, Nasun, Glass, Christopher K, and Gage, Fred H
- Subjects
Stem Cell Research ,Neurosciences ,Regenerative Medicine ,Aging ,Genetics ,Human Genome ,Underpinning research ,1.1 Normal biological development and functioning ,DNA Damage ,DNA Repair ,DNA ,Intergenic ,Deoxyuridine ,Embryonic Stem Cells ,Genome ,Human ,Genomic Instability ,Histones ,Humans ,Mitosis ,Mutation ,Nervous System Diseases ,Neurons ,Promoter Regions ,Genetic ,RNA-Binding Proteins ,Sequence Analysis ,DNA ,Transcription ,Genetic ,General Science & Technology - Abstract
Neurons are the longest-lived cells in our bodies and lack DNA replication, which makes them reliant on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, but we have limited knowledge of how genome instability emerges and what strategies neurons and other long-lived cells may have evolved to protect their genomes over the human life span. A targeted sequencing approach in human embryonic stem cell-induced neurons shows that, in neurons, DNA repair is enriched at well-defined hotspots that protect essential genes. These hotspots are enriched with histone H2A isoforms and RNA binding proteins and are associated with evolutionarily conserved elements of the human genome. These findings provide a basis for understanding genome integrity as it relates to aging and disease in the nervous system.
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- 2021
24. Biological age is increased by stress and restored upon recovery
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Poganik, Jesse R., Zhang, Bohan, Baht, Gurpreet S., Tyshkovskiy, Alexander, Deik, Amy, Kerepesi, Csaba, Yim, Sun Hee, Lu, Ake T., Haghani, Amin, Gong, Tong, Hedman, Anna M., Andolf, Ellika, Pershagen, Göran, Almqvist, Catarina, Clish, Clary B., Horvath, Steve, White, James P., and Gladyshev, Vadim N.
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- 2023
- Full Text
- View/download PDF
25. Epigenetic mutation load is weakly correlated with epigenetic age acceleration
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Yan, Qi, Paul, Kimberly C, Lu, Ake T, Kusters, Cynthia, Binder, Alexandra M, Horvath, Steve, and Ritz, Beate
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Biological Sciences ,Genetics ,Aging ,Human Genome ,stochastic epigenetic mutation ,epigenetic mutation load ,aging ,epigenetic clock ,DNA methylation ,Biochemistry and cell biology ,Clinical sciences - Abstract
DNA methylation (DNAm) age estimators are widely used to study aging-related conditions. It is not yet known whether DNAm age is associated with the accumulation of stochastic epigenetic mutations (SEMs), which reflect dysfunctions of the epigenetic maintenance system. Here, we defined epigenetic mutation load (EML) as the total number of SEMs per individual. We assessed associations between EML and DNAm age acceleration estimators using biweight midcorrelations in four population-based studies (total n = 6,388). EML was not only positively associated with chronological age (meta r = 0.171), but also with four measures of epigenetic age acceleration: the Horvath pan tissue clock, intrinsic epigenetic age acceleration, the Hannum clock, and the GrimAge clock (meta-analysis correlation ranging from r = 0.109 to 0.179). We further conducted pathway enrichment analyses for each participant's SEMs. The enrichment result demonstrated the stochasticity of epigenetic mutations, meanwhile implicated several pathways: signaling, neurogenesis, neurotransmitter, glucocorticoid, and circadian rhythm pathways may contribute to faster DNAm age acceleration. Finally, investigating genomic-region specific EML, we found that EMLs located within regions of transcriptional repression (TSS1500, TSS200, and 1stExon) were associated with faster age acceleration. Overall, our findings suggest a role for the accumulation of epigenetic mutations in the aging process.
- Published
- 2020
26. DNA methylation study of Huntington's disease and motor progression in patients and in animal models.
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Lu, Ake T, Narayan, Pritika, Grant, Matthew J, Langfelder, Peter, Wang, Nan, Kwak, Seung, Wilkinson, Hilary, Chen, Richard Z, Chen, Jian, Simon Bawden, C, Rudiger, Skye R, Ciosi, Marc, Chatzi, Afroditi, Maxwell, Alastair, Hore, Timothy A, Aaronson, Jeff, Rosinski, Jim, Preiss, Alicia, Vogt, Thomas F, Coppola, Giovanni, Monckton, Darren, Snell, Russell G, William Yang, X, and Horvath, Steve
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Animals ,Animals ,Genetically Modified ,Sheep ,Humans ,Mice ,Huntington Disease ,Disease Models ,Animal ,Disease Progression ,Recombinant Proteins ,Severity of Illness Index ,Registries ,Longitudinal Studies ,Follow-Up Studies ,Prospective Studies ,Cross-Sectional Studies ,Behavior ,Animal ,DNA Methylation ,Epigenesis ,Genetic ,CpG Islands ,Mutation ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Genome-Wide Association Study ,Young Adult ,Gene Knock-In Techniques ,Genetic Loci ,Huntingtin Protein ,Global Burden of Disease ,Genetically Modified ,Disease Models ,Animal ,Behavior ,Epigenesis ,Genetic ,and over - Abstract
Although Huntington's disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, and humans. Our epigenome-wide association study (EWAS) of human blood reveals that HD mutation status is significantly (p
- Published
- 2020
27. Epigenetic predictors of species maximum life span and other life-history traits in mammals
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Li, Caesar Z., primary, Haghani, Amin, additional, Yan, Qi, additional, Lu, Ake T., additional, Zhang, Joshua, additional, Fei, Zhe, additional, Ernst, Jason, additional, Yang, X. William, additional, Gladyshev, Vadim N., additional, Robeck, Todd R., additional, Chavez, Andreas S., additional, Cook, Joseph A., additional, Dunnum, Jonathan L., additional, Raj, Ken, additional, Seluanov, Andrei, additional, Gorbunova, Vera, additional, and Horvath, Steve, additional
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- 2024
- Full Text
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28. Effects of highly active antiretroviral therapy initiation on epigenomic DNA methylation in persons living with HIV
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Zhang, Joshua, primary, Sehl, Mary E., additional, Shih, Roger, additional, Breen, Elizabeth Crabb, additional, Li, Fengxue, additional, Lu, Ake T., additional, Bream, Jay H., additional, Duggal, Priya, additional, Martinson, Jeremy, additional, Wolinsky, Steven M., additional, Martinez-Maza, Otoniel, additional, Ramirez, Christina M., additional, Horvath, Steve, additional, and Jamieson, Beth D., additional
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- 2024
- Full Text
- View/download PDF
29. Longitudinal Epigenome-Wide Methylation Study of Cognitive Decline and Motor Progression in Parkinson’s Disease
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Chuang, Yu-Hsuan, Lu, Ake T, Paul, Kimberly C, Folle, Aline D, Bronstein, Jeff M, Bordelon, Yvette, Horvath, Steve, and Ritz, Beate
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Biomedical and Clinical Sciences ,Neurosciences ,Parkinson's Disease ,Brain Disorders ,Genetics ,Human Genome ,Neurodegenerative ,Aging ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Aged ,Apoptosis ,Cognitive Dysfunction ,DNA Methylation ,Disease Progression ,Epigenome ,Female ,Humans ,Longitudinal Studies ,Male ,Mitochondria ,Parkinson Disease ,Prognosis ,Proportional Hazards Models ,RNA ,Long Noncoding ,Receptor-Like Protein Tyrosine Phosphatases ,Class 8 ,Shab Potassium Channels ,Synapses ,Transferases ,Wnt Signaling Pathway ,Parkinson's disease ,disease progression ,longitudinal studies ,cognitive decline ,MMSE ,UPDRS ,DNA methylation ,Parkinson’s disease ,Biochemistry and Cell Biology - Abstract
BackgroundDNA methylation studies in Parkinson's disease (PD) thus far have focused on disease susceptibility but not progression.ObjectiveIn this epigenome-wide association study (EWAS), we aim to identify methylation markers associated with faster cognitive decline or motor progression in PD.MethodsWe included 232 PD patients from the Parkinson's Environment and Gene follow-up study who provided blood samples at enrolment. Information on cognitive and motor function was collected using the Mini-Mental State Examination (MMSE) and Unified Parkinson's Disease Rating Scale (UPDRS). For EWAS analyses, we used a robust measure of correlation: biweight midcorrelations, t-tests, and Cox proportional hazard models. We also conducted weighted correlation network analysis (WGCNA) to identify CpG modules associated with cognitive decline or motor progression in PD.ResultsAmong 197 individuals of European ancestry, with our EWAS approach we identified 7 genome-wide significant CpGs associated with a MMSE 4-point decline and 8 CpGs associated with faster motor progression (i.e., rate of UPDRS increase ≥5-point/year). The most interesting CpGs for cognitive decline include cg17445913 in KCNB1 (cor = 0.36, p = 6.85×10-7) and cg02920897 in DLEU2 (cor = 0.34, p = 3.23×10-6), while for motor progression it was cg01754178 in PTPRN2 (cor = - 0.34, p = 2.07×10-6). In WGCNA, motor progression related modules were enriched for genes related to neuronal synaptic functions, Wnt signaling pathway, and mitochondrial apoptosis.ConclusionsOur study provides the first epigenetic evidence that differential methylation in genes previously identified as being associated with cognitive impairment, neuronal synaptic function, Wnt signaling pathway, and mitochondrial apoptosis is associated with cognitive and motor progression in PD.
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- 2019
30. Association of subjective social status with epigenetic aging among Black and White women
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Hamlat, Elissa J., Adler, Nancy E., Laraia, Barbara, Surachman, Agus, Lu, Ake T., Zhang, Joshua, Horvath, Steve, and Epel, Elissa S.
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- 2022
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31. Significant variation in the performance of DNA methylation predictors across data preprocessing and normalization strategies
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Ori, Anil P. S., Lu, Ake T., Horvath, Steve, and Ophoff, Roel A.
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- 2022
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32. Author Correction: DNA methylation predicts age and provides insight into exceptional longevity of bats
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Wilkinson, Gerald S., Adams, Danielle M., Haghani, Amin, Lu, Ake T., Zoller, Joseph, Breeze, Charles E., Arnold, Bryan D., Ball, Hope C., Carter, Gerald G., Cooper, Lisa Noelle, Dechmann, Dina K. N., Devanna, Paolo, Fasel, Nicolas J., Galazyuk, Alexander V., Günther, Linus, Hurme, Edward, Jones, Gareth, Knörnschild, Mirjam, Lattenkamp, Ella Z., Li, Caesar Z., Mayer, Frieder, Reinhardt, Josephine A., Medellin, Rodrigo A., Nagy, Martina, Pope, Brian, Power, Megan L., Ransome, Roger D., Teeling, Emma C., Vernes, Sonja C., Zamora-Mejías, Daniel, Zhang, Joshua, Faure, Paul A., Greville, Lucas J., Herrera M., L. Gerardo, Flores-Martínez, José J., and Horvath, Steve
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- 2022
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33. Epigenetic aging of the demographically non-aging naked mole-rat
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Kerepesi, Csaba, Meer, Margarita V., Ablaeva, Julia, Amoroso, Vince G., Lee, Sang-Goo, Zhang, Bohan, Gerashchenko, Maxim V., Trapp, Alexandre, Yim, Sun Hee, Lu, Ake T., Levine, Morgan E., Seluanov, Andrei, Horvath, Steve, Park, Thomas J., Gorbunova, Vera, and Gladyshev, Vadim N.
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- 2022
- Full Text
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34. GWAS of epigenetic aging rates in blood reveals a critical role for TERT.
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Lu, Ake T, Xue, Luting, Salfati, Elias L, Chen, Brian H, Ferrucci, Luigi, Levy, Daniel, Joehanes, Roby, Murabito, Joanne M, Kiel, Douglas P, Tsai, Pei-Chien, Yet, Idil, Bell, Jordana T, Mangino, Massimo, Tanaka, Toshiko, McRae, Allan F, Marioni, Riccardo E, Visscher, Peter M, Wray, Naomi R, Deary, Ian J, Levine, Morgan E, Quach, Austin, Assimes, Themistocles, Tsao, Philip S, Absher, Devin, Stewart, James D, Li, Yun, Reiner, Alex P, Hou, Lifang, Baccarelli, Andrea A, Whitsel, Eric A, Aviv, Abraham, Cardona, Alexia, Day, Felix R, Wareham, Nicholas J, Perry, John RB, Ong, Ken K, Raj, Kenneth, Lunetta, Kathryn L, and Horvath, Steve
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Leukocytes ,Cells ,Cultured ,Telomere ,Fibroblasts ,Humans ,Telomerase ,DNA Methylation ,Epigenesis ,Genetic ,CpG Islands ,Aging ,Menopause ,Menarche ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Child ,Female ,Male ,Genome-Wide Association Study ,Young Adult ,Mendelian Randomization Analysis ,Cells ,Cultured ,Epigenesis ,Genetic ,and over - Abstract
DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) paradoxically confer higher IEAA (P
- Published
- 2018
35. DNA methylation-based surrogates of plasma proteins are associated with Parkinson's disease risk
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Fu, Katherine A., Paul, Kimberly C., Lu, Ake T., Horvath, Steve, Keener, Adrienne M., Bordelon, Yvette, Bronstein, Jeff M., and Ritz, Beate
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- 2021
- Full Text
- View/download PDF
36. Genetic architecture of epigenetic and neuronal ageing rates in human brain regions.
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Lu, Ake T, Hannon, Eilis, Levine, Morgan E, Crimmins, Eileen M, Lunnon, Katie, Mill, Jonathan, Geschwind, Daniel H, and Horvath, Steve
- Subjects
Brain ,Neurons ,Humans ,Neurodegenerative Diseases ,Calcium-Binding Proteins ,Nerve Tissue Proteins ,Brain Mapping ,DNA Methylation ,Epigenesis ,Genetic ,Aging ,Quantitative Trait Loci ,Genome ,Human ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Genome-Wide Association Study ,Cognitive Dysfunction ,Neurosciences ,Human Genome ,Genetics ,Prevention ,Neurological ,Epigenesis ,Genetic ,Genome ,Human ,and over ,Preschool ,MD Multidisciplinary - Abstract
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10-9) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10-20). Locus 1p36.12 is significantly associated (P=2.2 × 10-8) with epigenetic ageing of the prefrontal cortex, independent of the proportion of neurons. Our GWAS of the proportion of neurons identified two genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that overlaps significantly with sets found by GWAS of age-related macular degeneration (P=1.4 × 10-12), ulcerative colitis (P
- Published
- 2017
37. An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease
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Horvath, Steve, Gurven, Michael, Levine, Morgan E, Trumble, Benjamin C, Kaplan, Hillard, Allayee, Hooman, Ritz, Beate R, Chen, Brian, Lu, Ake T, Rickabaugh, Tammy M, Jamieson, Beth D, Sun, Dianjianyi, Li, Shengxu, Chen, Wei, Quintana-Murci, Lluis, Fagny, Maud, Kobor, Michael S, Tsao, Philip S, Reiner, Alexander P, Edlefsen, Kerstin L, Absher, Devin, and Assimes, Themistocles L
- Subjects
Cardiovascular ,Genetics ,Prevention ,Heart Disease - Coronary Heart Disease ,Clinical Research ,Aging ,Heart Disease ,Good Health and Well Being ,Black or African American ,Aged ,Coronary Disease ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Hispanic or Latino ,Humans ,Male ,Racial Groups ,Risk Factors ,Sex Characteristics ,United States ,White People ,DNA methylation ,Epigenetic clock ,Race ,Gender ,Coronary heart disease ,Hispanic paradox ,Black/white mortality cross-over ,Environmental Sciences ,Biological Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundEpigenetic biomarkers of aging (the "epigenetic clock") have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors.ResultsWe analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue.ConclusionsEpigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.
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- 2016
38. Coagulation factor VIII: Relationship to cardiovascular disease risk and whole genome sequence and epigenome‐wide analysis in African Americans
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Raffield, Laura M., Lu, Ake T., Szeto, Mindy D., Little, Amarise, Grinde, Kelsey E., Shaw, Jessica, Auer, Paul L., Cushman, Mary, Horvath, Steve, Irvin, Marguerite R., Lange, Ethan M., Lange, Leslie A., Nickerson, Deborah A., Thornton, Timothy A., Wilson, James G., Wheeler, Marsha M., Zakai, Neil A., and Reiner, Alex P.
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- 2020
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- View/download PDF
39. DNA methylation-based measures of biological age: meta-analysis predicting time to death
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Chen, Brian H, Marioni, Riccardo E, Colicino, Elena, Peters, Marjolein J, Ward-Caviness, Cavin K, Tsai, Pei-Chien, Roetker, Nicholas S, Just, Allan C, Demerath, Ellen W, Guan, Weihua, Bressler, Jan, Fornage, Myriam, Studenski, Stephanie, Vandiver, Amy R, Moore, Ann Zenobia, Tanaka, Toshiko, Kiel, Douglas P, Liang, Liming, Vokonas, Pantel, Schwartz, Joel, Lunetta, Kathryn L, Murabito, Joanne M, Bandinelli, Stefania, Hernandez, Dena G, Melzer, David, Nalls, Michael, Pilling, Luke C, Price, Timothy R, Singleton, Andrew B, Gieger, Christian, Holle, Rolf, Kretschmer, Anja, Kronenberg, Florian, Kunze, Sonja, Linseisen, Jakob, Meisinger, Christine, Rathmann, Wolfgang, Waldenberger, Melanie, Visscher, Peter M, Shah, Sonia, Wray, Naomi R, McRae, Allan F, Franco, Oscar H, Hofman, Albert, Uitterlinden, André G, Absher, Devin, Assimes, Themistocles, Levine, Morgan E, Lu, Ake T, Tsao, Philip S, Hou, Lifang, Manson, JoAnn E, Carty, Cara L, LaCroix, Andrea Z, Reiner, Alexander P, Spector, Tim D, Feinberg, Andrew P, Levy, Daniel, Baccarelli, Andrea, van Meurs, Joyce, Bell, Jordana T, Peters, Annette, Deary, Ian J, Pankow, James S, Ferrucci, Luigi, and Horvath, Steve
- Subjects
Biological Sciences ,Genetics ,Clinical Research ,Prevention ,Good Health and Well Being ,Aging ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Humans ,Logistic Models ,Male ,Mortality ,Racial Groups ,Risk Factors ,Survival Analysis ,T-Lymphocyte Subsets ,all-cause mortality ,lifespan ,epigenetics ,epigenetic clock ,DNA methylation ,mortality ,Biochemistry and cell biology ,Clinical sciences - Abstract
Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2x10-9), independent of chronological age, even after adjusting for additional risk factors (p
- Published
- 2016
40. Menopause accelerates biological aging.
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Levine, Morgan E, Lu, Ake T, Chen, Brian H, Hernandez, Dena G, Singleton, Andrew B, Ferrucci, Luigi, Bandinelli, Stefania, Salfati, Elias, Manson, JoAnn E, Quach, Austin, Kusters, Cynthia DJ, Kuh, Diana, Wong, Andrew, Teschendorff, Andrew E, Widschwendter, Martin, Ritz, Beate R, Absher, Devin, Assimes, Themistocles L, and Horvath, Steve
- Subjects
Humans ,Ovariectomy ,Epigenesis ,Genetic ,Aging ,Menopause ,Polymorphism ,Single Nucleotide ,Adult ,Middle Aged ,Female ,Mendelian Randomization Analysis ,DNA methylation ,WHI ,aging ,epigenetic clock ,menopause ,Contraception/Reproduction ,Estrogen ,Human Genome ,Genetics - Abstract
Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further.
- Published
- 2016
41. Correction to: Higher testosterone and testosterone/estradiol ratio in men are associated with decreased Pheno‑/GrimAge and DNA‑methylation based PAI1
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Kusters, Cynthia D. J., primary, Paul, Kimberly C., additional, Lu, Ake T., additional, Ferrucci, Luigi, additional, Ritz, Beate R., additional, Binder, Alexandra M., additional, and Horvath, Steve, additional
- Published
- 2023
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42. Correction: Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci
- Author
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Sugrue, Victoria J, primary, Zoller, Joseph Alan, additional, Narayan, Pritika, additional, Lu, Ake T, additional, Ortega-Recalde, Oscar J, additional, Grant, Matthew J, additional, Bawden, C Simon, additional, Rudiger, Skye R, additional, Haghani, Amin, additional, Bond, Donna M, additional, Hore, Reuben R, additional, Garratt, Michael, additional, Sears, Karen E, additional, Wang, Nan, additional, Yang, Xiangdong William, additional, Snell, Russell G, additional, Hore, Timothy A, additional, and Horvath, Steve, additional
- Published
- 2023
- Full Text
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43. Meta-analyses identify DNA methylation associated with kidney function and damage
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Schlosser, Pascal, Tin, Adrienne, Matias-Garcia, Pamela R., Thio, Chris H. L., Joehanes, Roby, Liu, Hongbo, Weihs, Antoine, Yu, Zhi, Hoppmann, Anselm, Grundner-Culemann, Franziska, Min, Josine L., Adeyemo, Adebowale A., Agyemang, Charles, Ärnlöv, Johan, Aziz, Nasir A., Baccarelli, Andrea, Bochud, Murielle, Brenner, Hermann, Breteler, Monique M. B., Carmeli, Cristian, Chaker, Layal, Chambers, John C., Cole, Shelley A., Coresh, Josef, Corre, Tanguy, Correa, Adolfo, Cox, Simon R., de Klein, Niek, Delgado, Graciela E., Domingo-Relloso, Arce, Eckardt, Kai-Uwe, Ekici, Arif B., Endlich, Karlhans, Evans, Kathryn L., Floyd, James S., Fornage, Myriam, Franke, Lude, Fraszczyk, Eliza, Gao, Xu, Gào, Xīn, Ghanbari, Mohsen, Ghasemi, Sahar, Gieger, Christian, Greenland, Philip, Grove, Megan L., Harris, Sarah E., Hemani, Gibran, Henneman, Peter, Herder, Christian, Horvath, Steve, Hou, Lifang, Hurme, Mikko A., Hwang, Shih-Jen, Jarvelin, Marjo-Riitta, Kardia, Sharon L. R., Kasela, Silva, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Kramer, Holly, Kronenberg, Florian, Kühnel, Brigitte, Lehtimäki, Terho, Lind, Lars, Liu, Dan, Liu, Yongmei, Lloyd-Jones, Donald M., Lohman, Kurt, Lorkowski, Stefan, Lu, Ake T., Marioni, Riccardo E., März, Winfried, McCartney, Daniel L., Meeks, Karlijn A. C., Milani, Lili, Mishra, Pashupati P., Nauck, Matthias, Navas-Acien, Ana, Nowak, Christoph, Peters, Annette, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ratliff, Scott M., Reiner, Alex P., Rosas, Sylvia E., Schöttker, Ben, Schwartz, Joel, Sedaghat, Sanaz, Smith, Jennifer A., Sotoodehnia, Nona, Stocker, Hannah R., Stringhini, Silvia, Sundström, Johan, Swenson, Brenton R., Tellez-Plaza, Maria, van Meurs, Joyce B. J., van Vliet-Ostaptchouk, Jana V., Venema, Andrea, Verweij, Niek, Walker, Rosie M., Wielscher, Matthias, Winkelmann, Juliane, Wolffenbuttel, Bruce H. R., Zhao, Wei, Zheng, Yinan, Loh, Marie, Snieder, Harold, Levy, Daniel, Waldenberger, Melanie, Susztak, Katalin, Köttgen, Anna, and Teumer, Alexander
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- 2021
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44. Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
- Author
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Tin, Adrienne, Schlosser, Pascal, Matias-Garcia, Pamela R., Thio, Chris H. L., Joehanes, Roby, Liu, Hongbo, Yu, Zhi, Weihs, Antoine, Hoppmann, Anselm, Grundner-Culemann, Franziska, Min, Josine L., Kuhns, Victoria L. Halperin, Adeyemo, Adebowale A., Agyemang, Charles, Ärnlöv, Johan, Aziz, Nasir A., Baccarelli, Andrea, Bochud, Murielle, Brenner, Hermann, Bressler, Jan, Breteler, Monique M. B., Carmeli, Cristian, Chaker, Layal, Coresh, Josef, Corre, Tanguy, Correa, Adolfo, Cox, Simon R., Delgado, Graciela E., Eckardt, Kai-Uwe, Ekici, Arif B., Endlich, Karlhans, Floyd, James S., Fraszczyk, Eliza, Gao, Xu, Gào, Xīn, Gelber, Allan C., Ghanbari, Mohsen, Ghasemi, Sahar, Gieger, Christian, Greenland, Philip, Grove, Megan L., Harris, Sarah E., Hemani, Gibran, Henneman, Peter, Herder, Christian, Horvath, Steve, Hou, Lifang, Hurme, Mikko A., Hwang, Shih-Jen, Kardia, Sharon L. R., Kasela, Silva, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Kronenberg, Florian, Kühnel, Brigitte, Ladd-Acosta, Christine, Lehtimäki, Terho, Lind, Lars, Liu, Dan, Lloyd-Jones, Donald M., Lorkowski, Stefan, Lu, Ake T., Marioni, Riccardo E., März, Winfried, McCartney, Daniel L., Meeks, Karlijn A. C., Milani, Lili, Mishra, Pashupati P., Nauck, Matthias, Nowak, Christoph, Peters, Annette, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ratliff, Scott M., Reiner, Alex P., Schöttker, Ben, Schwartz, Joel, Sedaghat, Sanaz, Smith, Jennifer A., Sotoodehnia, Nona, Stocker, Hannah R., Stringhini, Silvia, Sundström, Johan, Swenson, Brenton R., van Meurs, Joyce B. J., van Vliet-Ostaptchouk, Jana V., Venema, Andrea, Völker, Uwe, Winkelmann, Juliane, Wolffenbuttel, Bruce H. R., Zhao, Wei, Zheng, Yinan, Loh, Marie, Snieder, Harold, Waldenberger, Melanie, Levy, Daniel, Akilesh, Shreeram, Woodward, Owen M., Susztak, Katalin, Teumer, Alexander, and Köttgen, Anna
- Published
- 2021
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45. DNA methylation predicts age and provides insight into exceptional longevity of bats
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Wilkinson, Gerald S., Adams, Danielle M., Haghani, Amin, Lu, Ake T., Zoller, Joseph, Breeze, Charles E., Arnold, Bryan D., Ball, Hope C., Carter, Gerald G., Cooper, Lisa Noelle, Dechmann, Dina K. N., Devanna, Paolo, Fasel, Nicolas J., Galazyuk, Alexander V., Günther, Linus, Hurme, Edward, Jones, Gareth, Knörnschild, Mirjam, Lattenkamp, Ella Z., Li, Caesar Z., Mayer, Frieder, Reinhardt, Josephine A., Medellin, Rodrigo A., Nagy, Martina, Pope, Brian, Power, Megan L., Ransome, Roger D., Teeling, Emma C., Vernes, Sonja C., Zamora-Mejías, Daniel, Zhang, Joshua, Faure, Paul A., Greville, Lucas J., Herrera M., L. Gerardo, Flores-Martínez, José J., and Horvath, Steve
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- 2021
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46. Author Correction: DNA methylation predicts age and provides insight into exceptional longevity of bats
- Author
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Wilkinson, Gerald S., Adams, Danielle M., Haghani, Amin, Lu, Ake T., Zoller, Joseph, Breeze, Charles E., Arnold, Bryan D., Ball, Hope C., Carter, Gerald G., Cooper, Lisa Noelle, Dechmann, Dina K. N., Devanna, Paolo, Fasel, Nicolas J., Galazyuk, Alexander V., Günther, Linus, Hurme, Edward, Jones, Gareth, Knörnschild, Mirjam, Lattenkamp, Ella Z., Li, Caesar Z., Mayer, Frieder, Reinhardt, Josephine A., Medellin, Rodrigo A., Nagy, Martina, Pope, Brian, Power, Megan L., Ransome, Roger D., Teeling, Emma C., Vernes, Sonja C., Zamora-Mejías, Daniel, Zhang, Joshua, Faure, Paul A., Greville, Lucas J., Horvath, Steve, Herrera M., L. Gerardo, and Flores-Martínez, José J.
- Published
- 2021
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47. The cerebellum ages slowly according to the epigenetic clock
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Horvath, Steve, Mah, Vei, Lu, Ake T, Woo, Jennifer S, Choi, Oi-Wa, Jasinska, Anna J, Riancho, José A, Tung, Spencer, Coles, Natalie S, Braun, Jonathan, Vinters, Harry V, and Coles, L Stephen
- Subjects
Biological Sciences ,Genetics ,Aging ,Clinical Research ,Human Genome ,1.1 Normal biological development and functioning ,Underpinning research ,Generic health relevance ,Adult ,Aged ,80 and over ,Cerebellum ,Epigenesis ,Genetic ,Humans ,Middle Aged ,RNA Helicases ,Transcriptome ,tissue aging ,brain ,epigenetics ,biomarker of aging ,centenarian ,Biochemistry and cell biology ,Clinical sciences - Abstract
Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body. We used both transcriptional data and genetic data to elucidate molecular mechanisms which may explain this finding. The two largest superfamilies of helicases (SF1 and SF2) are significantly over-represented (p=9.2x10-9) among gene transcripts that are over-expressed in the cerebellum compared to other brain regions from the same subject. Furthermore, SNPs that are associated with epigenetic age acceleration in the cerebellum tend to be located near genes from helicase superfamilies SF1 and SF2 (enrichment p=5.8x10-3). Our genetic and transcriptional studies of epigenetic age acceleration support the hypothesis that the slow aging rate of the cerebellum is due to processes that involve RNA helicases.
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- 2015
48. Bloom syndrome patients and mice display accelerated epigenetic aging
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Lee, Jamie, primary, Zhang, Joshua, additional, Flanagan, Maeve, additional, Martinez, Julian A., additional, Cunniff, Christopher, additional, Kucine, Nicole, additional, Lu, Ake T., additional, Haghani, Amin, additional, Gordevičius, Juozas, additional, Horvath, Steve, additional, and Chang, Vivian Y., additional
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- 2023
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49. DNA methylation networks underlying mammalian traits
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Haghani, Amin, primary, Li, Caesar Z., additional, Robeck, Todd R., additional, Zhang, Joshua, additional, Lu, Ake T., additional, Ablaeva, Julia, additional, Acosta-Rodríguez, Victoria A., additional, Adams, Danielle M., additional, Alagaili, Abdulaziz N., additional, Almunia, Javier, additional, Aloysius, Ajoy, additional, Amor, Nabil M.S., additional, Ardehali, Reza, additional, Arneson, Adriana, additional, Baker, C. Scott, additional, Banks, Gareth, additional, Belov, Katherine, additional, Bennett, Nigel C., additional, Black, Peter, additional, Blumstein, Daniel T., additional, Bors, Eleanor K., additional, Breeze, Charles E., additional, Brooke, Robert T., additional, Brown, Janine L., additional, Carter, Gerald, additional, Caulton, Alex, additional, Cavin, Julie M., additional, Chakrabarti, Lisa, additional, Chatzistamou, Ioulia, additional, Chavez, Andreas S., additional, Chen, Hao, additional, Cheng, Kaiyang, additional, Chiavellini, Priscila, additional, Choi, Oi-Wa, additional, Clarke, Shannon, additional, Cook, Joseph A., additional, Cooper, Lisa N., additional, Cossette, Marie-Laurence, additional, Day, Joanna, additional, DeYoung, Joseph, additional, Dirocco, Stacy, additional, Dold, Christopher, additional, Dunnum, Jonathan L., additional, Ehmke, Erin E., additional, Emmons, Candice K., additional, Emmrich, Stephan, additional, Erbay, Ebru, additional, Erlacher-Reid, Claire, additional, Faulkes, Chris G., additional, Fei, Zhe, additional, Ferguson, Steven H., additional, Finno, Carrie J., additional, Flower, Jennifer E., additional, Gaillard, Jean-Michel, additional, Garde, Eva, additional, Gerber, Livia, additional, Gladyshev, Vadim N., additional, Goya, Rodolfo G., additional, Grant, Matthew J, additional, Green, Carla B., additional, Hanson, M. Bradley, additional, Hart, Daniel W., additional, Haulena, Martin, additional, Herrick, Kelsey, additional, Hogan, Andrew N., additional, Hogg, Carolyn J., additional, Hore, Timothy A., additional, Huang, Taosheng, additional, Izpisua Belmonte, Juan Carlos, additional, Jasinska, Anna J., additional, Jones, Gareth, additional, Jourdain, Eve, additional, Kashpur, Olga, additional, Katcher, Harold, additional, Katsumata, Etsuko, additional, Kaza, Vimala, additional, Kiaris, Hippokratis, additional, Kobor, Michael S., additional, Kordowitzki, Pawel, additional, Koski, William R., additional, Krützen, Michael, additional, Kwon, Soo Bin, additional, Larison, Brenda, additional, Lee, Sang-Goo, additional, Lehmann, Marianne, additional, Lemaître, Jean-François, additional, Levine, Andrew J., additional, Li, Xinmin, additional, Li, Cun, additional, Lim, Andrea R., additional, Lin, David T. S., additional, Lindemann, Dana M., additional, Liphardt, Schuyler W., additional, Little, Thomas J., additional, Macoretta, Nicholas, additional, Maddox, Dewey, additional, Matkin, Craig O., additional, Mattison, Julie A., additional, McClure, Matthew, additional, Mergl, June, additional, Meudt, Jennifer J., additional, Montano, Gisele A., additional, Mozhui, Khyobeni, additional, Munshi-South, Jason, additional, Murphy, William J., additional, Naderi, Asieh, additional, Nagy, Martina, additional, Narayan, Pritika, additional, Nathanielsz, Peter W., additional, Nguyen, Ngoc B., additional, Niehrs, Christof, additional, Nyamsuren, Batsaikhan, additional, O’Brien, Justine K., additional, Ginn, Perrie O’Tierney, additional, Odom, Duncan T, additional, Ophir, Alexander G., additional, Osborn, Steve, additional, Ostrander, Elaine A., additional, Parsons, Kim M., additional, Paul, Kimberly C., additional, Pedersen, Amy B., additional, Pellegrini, Matteo, additional, Peters, Katharina J., additional, Petersen, Jessica L., additional, Pietersen, Darren W., additional, Pinho, Gabriela M., additional, Plassais, Jocelyn, additional, Poganik, Jesse R., additional, Prado, Natalia A., additional, Reddy, Pradeep, additional, Rey, Benjamin, additional, Ritz, Beate R., additional, Robbins, Jooke, additional, Rodriguez, Magdalena, additional, Russell, Jennifer, additional, Rydkina, Elena, additional, Sailer, Lindsay L., additional, Salmon, Adam B., additional, Sanghavi, Akshay, additional, Schachtschneider, Kyle M., additional, Schmitt, Dennis, additional, Schmitt, Todd, additional, Schomacher, Lars, additional, Schook, Lawrence B., additional, Sears, Karen E., additional, Seifert, Ashley W., additional, Shafer, Aaron B.A., additional, Shindyapina, Anastasia V., additional, Simmons, Melanie, additional, Singh, Kavita, additional, Sinha, Ishani, additional, Slone, Jesse, additional, Snell, Russel G., additional, Soltanmohammadi, Elham, additional, Spangler, Matthew L., additional, Spriggs, Maria, additional, Staggs, Lydia, additional, Stedman, Nancy, additional, Steinman, Karen J., additional, Stewart, Donald T, additional, Sugrue, Victoria J., additional, Szladovits, Balazs, additional, Takahashi, Joseph S., additional, Takasugi, Masaki, additional, Teeling, Emma C., additional, Thompson, Michael J., additional, Van Bonn, Bill, additional, Vernes, Sonja C., additional, Villar, Diego, additional, Vinters, Harry V., additional, Vu, Ha, additional, Wallingford, Mary C., additional, Wang, Nan, additional, Wilkinson, Gerald S., additional, Williams, Robert W., additional, Yan, Qi, additional, Yao, Mingjia, additional, Young, Brent G., additional, Zhang, Bohan, additional, Zhang, Zhihui, additional, Zhao, Yang, additional, Zhao, Peng, additional, Zhou, Wanding, additional, Zoller, Joseph A., additional, Ernst, Jason, additional, Seluanov, Andrei, additional, Gorbunova, Vera, additional, Yang, X. William, additional, Raj, Ken, additional, and Horvath, Steve, additional
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- 2023
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50. Higher testosterone and testosterone/estradiol ratio in men are associated with decreased Pheno-/GrimAge and DNA-methylation based PAI1
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Kusters, Cynthia D. J., primary, Paul, Kimberly C., additional, Lu, Ake T., additional, Ferruci, Luigi, additional, Ritz, Beate R., additional, Binder, Alexandra M., additional, and Horvath, Steve, additional
- Published
- 2023
- Full Text
- View/download PDF
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