New Results
Universal DNA methylation age across mammalian tissues
A.T. Lu, Z. Fei, A. Haghani, T.R. Robeck, J.A. Zoller, C.Z. Li, R. Lowe, Q. Yan, J. Zhang, H. Vu, J. Ablaeva, V.A. Acosta-Rodriguez, D.M. Adams, J. Almunia, A. Aloysius, R. Ardehali, A. Arneson, C.S. Baker, G. Banks, K. Belov, N.C. Bennett, P. Black, D.T. Blumstein, E.K. Bors, C.E. Breeze, R.T. Brooke, J.L. Brown, G. Carter, A. Caulton, J.M. Cavin, L. Chakrabarti, I. Chatzistamou, H. Chen, K. Cheng, P. Chiavellini, O.W. Choi, S. Clarke, L.N. Cooper, M.L. Cossette, J. Day, J. DeYoung, S. DiRocco, C. Dold, E.E. Ehmke, C.K. Emmons, S. Emmrich, E. Erbay, C. Erlacher-Reid, C.G. Faulkes, S.H. Ferguson, C.J. Finno, J.E. Flower, J.M. Gaillard, E. Garde, L. Gerber, V.N. Gladyshev, V. Gorbunova, R.G. Goya, M.J. Grant, C.B. Green, E.N. Hales, M.B. Hanson, D.W. Hart, M. Haulena, K. Herrick, A.N. Hogan, C.J. Hogg, T.A. Hore, T. Huang, J.C. Izpisua Belmonte, A.J. Jasinska, G. Jones, E. Jourdain, O. Kashpur, H. Katcher, E. Katsumata, V. Kaza, H. Kiaris, M.S. Kobor, P. Kordowitzki, W.R. Koski, M. Kruetzen, S.B. Kwon, B. Larison, S.G. Lee, M. Lehmann, J.F. Lemaitre, A.J. Levine, C. Li, X. Li, A.R. Lim, D.T.S. Lin, D.M. Lindemann, T.J. Little, N. Macoretta, D. Maddox, C.O. Matkin, J.A. Mattison, M. McClure, J. Mergl, J.J. Meudt, G.A. Montano, K. Mozhui, J. Munshi-South, A. Naderi, M. Nagy, P. Narayan, P.W. Nathanielsz, N.B. Nguyen, C. Niehrs, J.K. O’Brien, P. O’Tierney Ginn, D.T. Odom, A.G. Ophir, S. Osborn, E.A. Ostrander, K.M. Parsons, K.C. Paul, M. Pellegrini, K.J. Peters, A.B. Pedersen, J.L. Petersen, D.W. Pietersen, G.M. Pinho, J. Plassais, J.R. Poganik, N.A. Prado, P. Reddy, B. Rey, B.R. Ritz, J. Robbins, M. Rodriguez, J. Russell, E. Rydkina, L.L. Sailer, A.B. Salmon, A. Sanghavi, K.M. Schachtschneider, D. Schmitt, T. Schmitt, L. Schomacher, L.B. Schook, K.E. Sears, A.W. Seifert, A. Seluanov, A.B.A. Shafer, D. Shanmuganayagam, A.V. Shindyapina, M. Simmons, K. Singh, I. Sinha, J. Slone, R.G. Snell, E. Soltanmaohammadi, M.L. Spangler, M.C. Spriggs, L. Staggs, N. Stedman, K.J. Steinman, D.T. Stewart, V.J. Sugrue, B. Szladovits, J.S. Takahashi, M. Takasugi, E.C. Teeling, M.J. Thompson, B. Van Bonn, S.C. Vernes, D. Villar, H.V. Vinters, M.C. Wallingford, N. Wang, R.K. Wayne, G.S. Wilkinson, C.K. Williams, R.W. Williams, X.W. Yang, M. Yao, B.G. Young, B. Zhang, Z. Zhang, P. Zhao, Y. Zhao, W. Zhou, J. Zimmermann, J. Ernst, K. Raj, S. Horvath
doi: https://doi.org/10.1101/2021.01.18.426733
A.T. Lu
1Dept. of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
2Altos Labs, San Diego, CA, USA
Z. Fei
3Dept. of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
A. Haghani
1Dept. of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
2Altos Labs, San Diego, CA, USA
T.R. Robeck
4Zoological SeaWorld Parks and Entertainment, Orlando, Florida, USA
J.A. Zoller
3Dept. of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
C.Z. Li
3Dept. of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
R. Lowe
5Altos Labs, Cambridge Institute of Science, Cambridge CB25 6GP United Kingdom
Q. Yan
2Altos Labs, San Diego, CA, USA
J. Zhang
1Dept. of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
H. Vu
6Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA
J. Ablaeva
7Dept. of Biology, University of Rochester, Rochester, NY, USA
V.A. Acosta-Rodriguez
8Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, US
D.M. Adams
9Dept. of Biology, University of Maryland, College Park, USA
J. Almunia
10Loro Parque Fundacion, Avenida Loro Parque, Puerto de la Cruz, Tenerife, Spain
A. Aloysius
11Department of Biology, University of Kentucky, Lexington, KY, USA
R. Ardehali
12Division of Cardiology, Dept. of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
A. Arneson
6Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA
13Dept. of Biological Chemistry, University of California, Los Angeles, Los Angeles, California, USA
C.S. Baker
14Marine Mammal Institute, Oregon State University, Newport, OR, USA
G. Banks
15Mammalian Genetics Unit, MRC Harwell Institute, Harwell Science and Innovation Campus, Oxfordshire, UK
K. Belov
16School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia
N.C. Bennett
17Department of Zoology and Entomology, University of Pretoria, Private Bag X20, Hatfield, 0028, South Africa
P. Black
18Busch Gardens Tampa, Tampa, Florida, USA
D.T. Blumstein
19Dept. of Ecology and Evolutionary Biology, UCLA, Los Angeles, CA, USA
20Rocky Mountain Biological Laboratory, Crested Butte, CO, USA
E.K. Bors
14Marine Mammal Institute, Oregon State University, Newport, OR, USA
C.E. Breeze
21Altius Institute for Biomedical Sciences, Seattle, WA, USA
R.T. Brooke
22Epigenetic Clock Development Foundation, Los Angeles, CA, USA
J.L. Brown
23Center for Species Survival, Smithsonian Conservation Biology Institute, Front Royal, VA, USA
G. Carter
24Department of Evolution, Ecology and Organismal Biology, The Ohio State University,Columbus, OH, USA
A. Caulton
25AgResearch, Invermay Agricultural Centre, Mosgiel, Otago, New Zealand
26Dept. of Biochemistry, University of Otago, Dunedin, Otago, New Zealand
J.M. Cavin
27Gulf World, Dolphin Company, USA
L. Chakrabarti
28School of Veterinary Medicine and Science, University of Nottingham, UK
I. Chatzistamou
29Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, SC, USA
H. Chen
30Dept. of Pharmacology, Addiction Science and Toxicology, The University of Tennessee Health Science Center, Memphis, TN, USA
K. Cheng
31Medical Informatics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
P. Chiavellini
32Biochemistry Research Institute of La Plata, Histology and Pathology, School of Medicine, University of La Plata, La Plata, Argentina
O.W. Choi
33Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Dept. of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
S. Clarke
25AgResearch, Invermay Agricultural Centre, Mosgiel, Otago, New Zealand
L.N. Cooper
34Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, USA
M.L. Cossette
35Department of Environmental & Life Sciences, Trent University, Peterborough Ontario, Canada K9J 7B8
J. Day
36Taronga Institute of Science and Learning, Taronga Conservation Society Australia, New South Wales, Australia
J. DeYoung
33Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Dept. of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
S. DiRocco
37SeaWorld of Florida, SeaWorld Drive, Orlando, Florida, USA
C. Dold
38Zoological Operations, SeaWorld Parks and Entertainment, Orlando, Florida, USA
E.E. Ehmke
39Duke Lemur Center, Durham, North Carolina, USA
C.K. Emmons
40Conservation Biology Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, Seattle, Washington, USA
S. Emmrich
41Depts. of Biology and Medicine, University of Rochester, Rochester, NY, USA
E. Erbay
42Altos Labs, San Francisco, USA
C. Erlacher-Reid
43SeaWorld Orlando, 7007 SeaWorld Drive, Orlando, FL USA
C.G. Faulkes
44School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
S.H. Ferguson
45Fisheries and Oceans Canada, Freshwater Institute, Winnipeg, Canada
46Dept. of Biological Sciences, University of Manitoba, Winnipeg, Canada
C.J. Finno
47Dept. of Population Health and Reproduction, University of California, Davis School of Veterinary Medicine, Davis, CA, USA
J.E. Flower
48Mystic Aquarium, Mystic, Connecticut, USA
J.M. Gaillard
49Universite de Lyon, Universite Lyon 1, CNRS, Laboratoire de Biometrie et Biologie Evolutive, Villeurbanne, France
E. Garde
50Greenland Institute of Natural Resources, Nuuk, Greenland
L. Gerber
51School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, Australia
52Evolutionary Genetics Group, Department of Anthropology, University of Zurich, Zurich, Switzerland
V.N. Gladyshev
53Division of Genetics, Dept. of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
V. Gorbunova
41Depts. of Biology and Medicine, University of Rochester, Rochester, NY, USA
R.G. Goya
32Biochemistry Research Institute of La Plata, Histology and Pathology, School of Medicine, University of La Plata, La Plata, Argentina
M.J. Grant
54Applied Translational Genetics Group, School of Biological Sciences, Centre for Brain Research, The University of Auckland, Auckland, New Zealand
C.B. Green
55Department of Neuroscience, Peter ODonnell Jr. Brain Institute, University of Texas Southwestern Medical Center , Dallas, TX, 75390-9111, USA
E.N. Hales
47Dept. of Population Health and Reproduction, University of California, Davis School of Veterinary Medicine, Davis, CA, USA
M.B. Hanson
40Conservation Biology Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, Seattle, Washington, USA
D.W. Hart
17Department of Zoology and Entomology, University of Pretoria, Private Bag X20, Hatfield, 0028, South Africa
M. Haulena
56Vancouver Aquarium, Vancouver, Canada
K. Herrick
57SeaWorld of California, California, USA
A.N. Hogan
58Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
C.J. Hogg
16School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia
T.A. Hore
59Dept. of Anatomy, University of Otago, Dunedin, New Zealand
T. Huang
60Division of Human Genetics, Department of Pediatrics, University at Buffalo, New York, USA
61Division of Genetics & Metabolism, Oishei Children’s Hospital, Buffalo, New York, USA
J.C. Izpisua Belmonte
2Altos Labs, San Diego, CA, USA
A.J. Jasinska
33Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Dept. of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
G. Jones
62School of Biological Sciences, University of Bristol, Bristol, UK
E. Jourdain
63Norwegian Orca Survey, Andenes, Norway
O. Kashpur
64Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA
H. Katcher
65Yuvan Research, Mountain View, CA, USA
E. Katsumata
66Kamogawa Sea World, Kamogawa, Chiba, Japan
V. Kaza
67Peromyscus Genetic Stock Center, University of South Carolina, SC, USA
H. Kiaris
67Peromyscus Genetic Stock Center, University of South Carolina, SC, USA
68Dept. of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, SC, USA
M.S. Kobor
69Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, Canada
P. Kordowitzki
70Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Poland
71Institute for Veterinary Medicine, Nicolaus Copernicus University, Torun, Poland
W.R. Koski
72LGL Limited, King City, ON, Canada
M. Kruetzen
52Evolutionary Genetics Group, Department of Anthropology, University of Zurich, Zurich, Switzerland
S.B. Kwon
6Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA
13Dept. of Biological Chemistry, University of California, Los Angeles, Los Angeles, California, USA
B. Larison
19Dept. of Ecology and Evolutionary Biology, UCLA, Los Angeles, CA, USA
73Center for Tropical Research, Institute for the Environment and Sustainability, UCLA, Los Angeles, CA, USA
S.G. Lee
53Division of Genetics, Dept. of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
M. Lehmann
32Biochemistry Research Institute of La Plata, Histology and Pathology, School of Medicine, University of La Plata, La Plata, Argentina
J.F. Lemaitre
49Universite de Lyon, Universite Lyon 1, CNRS, Laboratoire de Biometrie et Biologie Evolutive, Villeurbanne, France
A.J. Levine
74Dept. of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
C. Li
75Texas Pregnancy and Life-course Health Center, Southwest National Primate Research Center, San Antonio, Texas, USA
76Dept. of Animal Science, College of Agriculture and Natural Resources; Dept., Laramie, Wyoming, USA
X. Li
77Technology Center for Genomics and Bioinformatics, Dept. of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA
A.R. Lim
1Dept. of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
D.T.S. Lin
69Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, Canada
D.M. Lindemann
37SeaWorld of Florida, SeaWorld Drive, Orlando, Florida, USA
T.J. Little
78Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
N. Macoretta
41Depts. of Biology and Medicine, University of Rochester, Rochester, NY, USA
D. Maddox
79White Oak Conservation, Yulee FL, USA
C.O. Matkin
80North Gulf Oceanic Society, Homer, Alaska,USA
J.A. Mattison
81Translational Gerontology Branch, National Institute on Aging Intramural Research Program, National Institutes of Health, USA
M. McClure
82ABS Global, DeForest, WI, USA
J. Mergl
83Marineland of Canada, Niagara Falls, Ontario, Canada
J.J. Meudt
84Biomedical and Genomic Research Group, Dept. of Animal and Dairy Sciences, University of Wisconsin Madison, Madison, Wisconsin, US
G.A. Montano
38Zoological Operations, SeaWorld Parks and Entertainment, Orlando, Florida, USA
K. Mozhui
85Dept. of Preventive Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA
86Dept. of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA
J. Munshi-South
87Louis Calder Center - Biological Field Station, Department of Biological Sciences, Fordham University, Armonk, NY USA
A. Naderi
68Dept. of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, SC, USA
M. Nagy
88Museum fur Naturkunde, Leibniz-Institute for Evolution and Biodiversity Science, Berlin, Germany
P. Narayan
54Applied Translational Genetics Group, School of Biological Sciences, Centre for Brain Research, The University of Auckland, Auckland, New Zealand
P.W. Nathanielsz
75Texas Pregnancy and Life-course Health Center, Southwest National Primate Research Center, San Antonio, Texas, USA
89Dept. of Animal Science, College of Agriculture and Natural Resources, Laramie, Wyoming, USA
N.B. Nguyen
12Division of Cardiology, Dept. of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
C. Niehrs
90Institute of Molecular Biology (IMB), Mainz, Germany
91Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany
J.K. O’Brien
36Taronga Institute of Science and Learning, Taronga Conservation Society Australia, New South Wales, Australia
P. O’Tierney Ginn
64Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA
92Dept Obstetrics & Gynecology, Tufts University School of Medicine, Boston, MA, USA
D.T. Odom
93Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK
94Deutsches Krebsforschungszentrum, Division of Regulatory Genomics and Cancer Evolution - B270, Im Neuenheimer Feld 280, Heidelberg, Germany
A.G. Ophir
95Dept. of Psychology, Cornell University, Ithaca, NY, USA
S. Osborn
96SeaWorld of Texas, San Antonio, Texas, USA
E.A. Ostrander
58Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
K.M. Parsons
40Conservation Biology Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, Seattle, Washington, USA
K.C. Paul
74Dept. of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
M. Pellegrini
97Dept. Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA
K.J. Peters
52Evolutionary Genetics Group, Department of Anthropology, University of Zurich, Zurich, Switzerland
98School of Earth and Environment, University of Canterbury, Christchurch, New Zealand
A.B. Pedersen
78Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
J.L. Petersen
99Dept. of Animal Science, University of Nebraska, Lincoln, USA
D.W. Pietersen
100Mammal Research Institute, Department of Zoology and Entomology, University of Pretoria, Private Bag X20, Hatfield, 0028, South Africa
G.M. Pinho
19Dept. of Ecology and Evolutionary Biology, UCLA, Los Angeles, CA, USA
J. Plassais
58Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
J.R. Poganik
53Division of Genetics, Dept. of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
N.A. Prado
101Department of Biology, College of Arts and Science, Adelphi University. One South Avenue, Garden City, NY, USA
P. Reddy
102Salk Institute for Biological Studies, La Jolla, CA USA
B. Rey
49Universite de Lyon, Universite Lyon 1, CNRS, Laboratoire de Biometrie et Biologie Evolutive, Villeurbanne, France
B.R. Ritz
103Dept. of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA
104Dept. of Environmental Health Sciences, UCLA Fielding School of Public Health, Los Angeles, CA, USA
105Dept. of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA
J. Robbins
106Center for Coastal Studies, Provincetown, MA, USA
M. Rodriguez
107Miami Seaquarium, Miami, Florida, USA
J. Russell
108SeaWorld San Diego, San Diego, CA, USA
E. Rydkina
41Depts. of Biology and Medicine, University of Rochester, Rochester, NY, USA
L.L. Sailer
95Dept. of Psychology, Cornell University, Ithaca, NY, USA
A.B. Salmon
109The Sam and Ann Barshop Institute for Longevity and Aging Studies, and Dept. of Molecular Medicine, UT Health San Antonio, and the Geriatric Research Education and Clinical Center, South Texas Veterans Healthcare System, San Antonio TX, USA
A. Sanghavi
65Yuvan Research, Mountain View, CA, USA
K.M. Schachtschneider
110Dept. of Radiology, University of Illinois at Chicago, Chicago, IL, USA
111Dept. of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA
112National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL
D. Schmitt
113College of Agriculture, Missouri State University, USA
T. Schmitt
57SeaWorld of California, California, USA
L. Schomacher
114Institute of Molecular Biology gGmbH, Mainz, Germany
L.B. Schook
110Dept. of Radiology, University of Illinois at Chicago, Chicago, IL, USA
115Dept. of Animal Sciences, University of Illinois at Urbana-Champaign, USA
K.E. Sears
19Dept. of Ecology and Evolutionary Biology, UCLA, Los Angeles, CA, USA
A.W. Seifert
11Department of Biology, University of Kentucky, Lexington, KY, USA
A. Seluanov
41Depts. of Biology and Medicine, University of Rochester, Rochester, NY, USA
A.B.A. Shafer
116Department of Forensic Science, Environmental & Life Sciences, Trent University, Peterborough Ontario, Canada K9J 7B8
D. Shanmuganayagam
84Biomedical and Genomic Research Group, Dept. of Animal and Dairy Sciences, University of Wisconsin Madison, Madison, Wisconsin, US
117Dept. of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
A.V. Shindyapina
53Division of Genetics, Dept. of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
M. Simmons
39Duke Lemur Center, Durham, North Carolina, USA
K. Singh
118Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’S NMIMS University, Mumbai, India
I. Sinha
19Dept. of Ecology and Evolutionary Biology, UCLA, Los Angeles, CA, USA
J. Slone
60Division of Human Genetics, Department of Pediatrics, University at Buffalo, New York, USA
R.G. Snell
54Applied Translational Genetics Group, School of Biological Sciences, Centre for Brain Research, The University of Auckland, Auckland, New Zealand
E. Soltanmaohammadi
68Dept. of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, SC, USA
M.L. Spangler
99Dept. of Animal Science, University of Nebraska, Lincoln, USA
M.C. Spriggs
18Busch Gardens Tampa, Tampa, Florida, USA
L. Staggs
37SeaWorld of Florida, SeaWorld Drive, Orlando, Florida, USA
N. Stedman
18Busch Gardens Tampa, Tampa, Florida, USA
K.J. Steinman
119Species Preservation Laboratory, SeaWorld San Diego, California, USA
D.T. Stewart
120Biology Department, Acadia University, Wolfville, Nova Scotia, Canada B4P 2R6
V.J. Sugrue
59Dept. of Anatomy, University of Otago, Dunedin, New Zealand
B. Szladovits
121Dept. of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, UK
J.S. Takahashi
8Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, US
122Howard Hughes Medical Institute, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, USA
M. Takasugi
41Depts. of Biology and Medicine, University of Rochester, Rochester, NY, USA
E.C. Teeling
123School of Biology and Environmental Science, University College Dublin, Belfield, Dublin, Ireland
M.J. Thompson
97Dept. Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA
B. Van Bonn
124John G. Shedd Aquarium, Chicago, Illinois, USA
S.C. Vernes
125School of Biology, The University of St Andrews, Fife, UK
126Neurogenetics of Vocal Communication Group, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands
D. Villar
127Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
H.V. Vinters
128Dept. of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, USA
M.C. Wallingford
64Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA
129Division of Obstetrics and Gynecology, Tufts University School of Medicine,Boston, MA, USA
N. Wang
130Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA
131Dept. of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
R.K. Wayne
19Dept. of Ecology and Evolutionary Biology, UCLA, Los Angeles, CA, USA
G.S. Wilkinson
9Dept. of Biology, University of Maryland, College Park, USA
C.K. Williams
74Dept. of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
R.W. Williams
86Dept. of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA
X.W. Yang
130Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA
131Dept. of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
M. Yao
3Dept. of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
B.G. Young
132Fisheries and Oceans Canada, University Crescent, Winnipeg, Canada
B. Zhang
53Division of Genetics, Dept. of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Z. Zhang
41Depts. of Biology and Medicine, University of Rochester, Rochester, NY, USA
P. Zhao
12Division of Cardiology, Dept. of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
133Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, USA
Y. Zhao
41Depts. of Biology and Medicine, University of Rochester, Rochester, NY, USA
W. Zhou
134Center for Computational and Genomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, USA
135Dept. of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA
J. Zimmermann
136Institute for Computer Science, University of Bonn, Germany
J. Ernst
6Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA
13Dept. of Biological Chemistry, University of California, Los Angeles, Los Angeles, California, USA
K. Raj
5Altos Labs, Cambridge Institute of Science, Cambridge CB25 6GP United Kingdom
S. Horvath
1Dept. of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
2Altos Labs, San Diego, CA, USA
3Dept. of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
ABSTRACT
Aging is often perceived as a degenerative process resulting from random accrual of cellular damage over time. Despite this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, we hypothesized that one can build pan-mammalian clocks that measure age in all mammalian species. To address this, we generated data using 11,754 methylation arrays, each profiling up to 36 thousand cytosines in highly-conserved stretches of DNA, from 59 tissue-types derived from 185 mammalian species. From these methylation profiles, we constructed three age predictors, each with a single mathematical formula, termed universal pan-mammalian clocks that are accurate in estimating the age (r>0.96) of any mammalian tissue. Deviations between epigenetic age and chronological age relate to mortality risk in humans, mutations that affect the somatotropic axis in mice, and caloric restriction. We characterized specific cytosines, whose methylation levels change with age across most mammalian species. These cytosines are greatly enriched in polycomb repressive complex 2-binding sites, are located in regions that gradually lose chromatin accessibility with age and are proximal to genes that play a role in mammalian development, cancer, human obesity, and human longevity. Collectively, these results support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new compelling evidence.
SUMMARY This study identifies and characterizes evolutionarily conserved cytosines implicated in the aging process across mammals and establishes pan mammalian epigenetic clocks.
Competing Interest Statement
SH is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several patents from his employer UC Regents. These patents list SH, JE and AA as inventors. The other authors declare no conflicts of interest.
Footnotes
↵# Joint First or Last authors
All sections updated with more species and samples. New sections added for analysis in human mortality, OSKM-based reprogramming, transgenic mice for studying the somatotropic axis, overlap with late-replicating domains, TF enrichment and single cell ATAC seq analysis of human bone marrow.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Posted September 05, 2022.
Universal DNA methylation age across mammalian tissues
A.T. Lu, Z. Fei, A. Haghani, T.R. Robeck, J.A. Zoller, C.Z. Li, R. Lowe, Q. Yan, J. Zhang, H. Vu, J. Ablaeva, V.A. Acosta-Rodriguez, D.M. Adams, J. Almunia, A. Aloysius, R. Ardehali, A. Arneson, C.S. Baker, G. Banks, K. Belov, N.C. Bennett, P. Black, D.T. Blumstein, E.K. Bors, C.E. Breeze, R.T. Brooke, J.L. Brown, G. Carter, A. Caulton, J.M. Cavin, L. Chakrabarti, I. Chatzistamou, H. Chen, K. Cheng, P. Chiavellini, O.W. Choi, S. Clarke, L.N. Cooper, M.L. Cossette, J. Day, J. DeYoung, S. DiRocco, C. Dold, E.E. Ehmke, C.K. Emmons, S. Emmrich, E. Erbay, C. Erlacher-Reid, C.G. Faulkes, S.H. Ferguson, C.J. Finno, J.E. Flower, J.M. Gaillard, E. Garde, L. Gerber, V.N. Gladyshev, V. Gorbunova, R.G. Goya, M.J. Grant, C.B. Green, E.N. Hales, M.B. Hanson, D.W. Hart, M. Haulena, K. Herrick, A.N. Hogan, C.J. Hogg, T.A. Hore, T. Huang, J.C. Izpisua Belmonte, A.J. Jasinska, G. Jones, E. Jourdain, O. Kashpur, H. Katcher, E. Katsumata, V. Kaza, H. Kiaris, M.S. Kobor, P. Kordowitzki, W.R. Koski, M. Kruetzen, S.B. Kwon, B. Larison, S.G. Lee, M. Lehmann, J.F. Lemaitre, A.J. Levine, C. Li, X. Li, A.R. Lim, D.T.S. Lin, D.M. Lindemann, T.J. Little, N. Macoretta, D. Maddox, C.O. Matkin, J.A. Mattison, M. McClure, J. Mergl, J.J. Meudt, G.A. Montano, K. Mozhui, J. Munshi-South, A. Naderi, M. Nagy, P. Narayan, P.W. Nathanielsz, N.B. Nguyen, C. Niehrs, J.K. O’Brien, P. O’Tierney Ginn, D.T. Odom, A.G. Ophir, S. Osborn, E.A. Ostrander, K.M. Parsons, K.C. Paul, M. Pellegrini, K.J. Peters, A.B. Pedersen, J.L. Petersen, D.W. Pietersen, G.M. Pinho, J. Plassais, J.R. Poganik, N.A. Prado, P. Reddy, B. Rey, B.R. Ritz, J. Robbins, M. Rodriguez, J. Russell, E. Rydkina, L.L. Sailer, A.B. Salmon, A. Sanghavi, K.M. Schachtschneider, D. Schmitt, T. Schmitt, L. Schomacher, L.B. Schook, K.E. Sears, A.W. Seifert, A. Seluanov, A.B.A. Shafer, D. Shanmuganayagam, A.V. Shindyapina, M. Simmons, K. Singh, I. Sinha, J. Slone, R.G. Snell, E. Soltanmaohammadi, M.L. Spangler, M.C. Spriggs, L. Staggs, N. Stedman, K.J. Steinman, D.T. Stewart, V.J. Sugrue, B. Szladovits, J.S. Takahashi, M. Takasugi, E.C. Teeling, M.J. Thompson, B. Van Bonn, S.C. Vernes, D. Villar, H.V. Vinters, M.C. Wallingford, N. Wang, R.K. Wayne, G.S. Wilkinson, C.K. Williams, R.W. Williams, X.W. Yang, M. Yao, B.G. Young, B. Zhang, Z. Zhang, P. Zhao, Y. Zhao, W. Zhou, J. Zimmermann, J. Ernst, K. Raj, S. Horvath
bioRxiv 2021.01.18.426733; doi: https://doi.org/10.1101/2021.01.18.426733
Universal DNA methylation age across mammalian tissues
A.T. Lu, Z. Fei, A. Haghani, T.R. Robeck, J.A. Zoller, C.Z. Li, R. Lowe, Q. Yan, J. Zhang, H. Vu, J. Ablaeva, V.A. Acosta-Rodriguez, D.M. Adams, J. Almunia, A. Aloysius, R. Ardehali, A. Arneson, C.S. Baker, G. Banks, K. Belov, N.C. Bennett, P. Black, D.T. Blumstein, E.K. Bors, C.E. Breeze, R.T. Brooke, J.L. Brown, G. Carter, A. Caulton, J.M. Cavin, L. Chakrabarti, I. Chatzistamou, H. Chen, K. Cheng, P. Chiavellini, O.W. Choi, S. Clarke, L.N. Cooper, M.L. Cossette, J. Day, J. DeYoung, S. DiRocco, C. Dold, E.E. Ehmke, C.K. Emmons, S. Emmrich, E. Erbay, C. Erlacher-Reid, C.G. Faulkes, S.H. Ferguson, C.J. Finno, J.E. Flower, J.M. Gaillard, E. Garde, L. Gerber, V.N. Gladyshev, V. Gorbunova, R.G. Goya, M.J. Grant, C.B. Green, E.N. Hales, M.B. Hanson, D.W. Hart, M. Haulena, K. Herrick, A.N. Hogan, C.J. Hogg, T.A. Hore, T. Huang, J.C. Izpisua Belmonte, A.J. Jasinska, G. Jones, E. Jourdain, O. Kashpur, H. Katcher, E. Katsumata, V. Kaza, H. Kiaris, M.S. Kobor, P. Kordowitzki, W.R. Koski, M. Kruetzen, S.B. Kwon, B. Larison, S.G. Lee, M. Lehmann, J.F. Lemaitre, A.J. Levine, C. Li, X. Li, A.R. Lim, D.T.S. Lin, D.M. Lindemann, T.J. Little, N. Macoretta, D. Maddox, C.O. Matkin, J.A. Mattison, M. McClure, J. Mergl, J.J. Meudt, G.A. Montano, K. Mozhui, J. Munshi-South, A. Naderi, M. Nagy, P. Narayan, P.W. Nathanielsz, N.B. Nguyen, C. Niehrs, J.K. O’Brien, P. O’Tierney Ginn, D.T. Odom, A.G. Ophir, S. Osborn, E.A. Ostrander, K.M. Parsons, K.C. Paul, M. Pellegrini, K.J. Peters, A.B. Pedersen, J.L. Petersen, D.W. Pietersen, G.M. Pinho, J. Plassais, J.R. Poganik, N.A. Prado, P. Reddy, B. Rey, B.R. Ritz, J. Robbins, M. Rodriguez, J. Russell, E. Rydkina, L.L. Sailer, A.B. Salmon, A. Sanghavi, K.M. Schachtschneider, D. Schmitt, T. Schmitt, L. Schomacher, L.B. Schook, K.E. Sears, A.W. Seifert, A. Seluanov, A.B.A. Shafer, D. Shanmuganayagam, A.V. Shindyapina, M. Simmons, K. Singh, I. Sinha, J. Slone, R.G. Snell, E. Soltanmaohammadi, M.L. Spangler, M.C. Spriggs, L. Staggs, N. Stedman, K.J. Steinman, D.T. Stewart, V.J. Sugrue, B. Szladovits, J.S. Takahashi, M. Takasugi, E.C. Teeling, M.J. Thompson, B. Van Bonn, S.C. Vernes, D. Villar, H.V. Vinters, M.C. Wallingford, N. Wang, R.K. Wayne, G.S. Wilkinson, C.K. Williams, R.W. Williams, X.W. Yang, M. Yao, B.G. Young, B. Zhang, Z. Zhang, P. Zhao, Y. Zhao, W. Zhou, J. Zimmermann, J. Ernst, K. Raj, S. Horvath
bioRxiv 2021.01.18.426733; doi: https://doi.org/10.1101/2021.01.18.426733
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