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 G Carter
,
A Caulton
,
J M Cavin
,
L Chakrabarti
,
I Chatzistamou
,
H Chen
,
K Cheng
,
P Chiavellini
,
O W Choi
,
S M 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 Krützen
,
S B Kwon
,
B Larison
,
S G Lee
,
M Lehmann
,
Jean-François Lemaître Lemaître
(1, 2, 3)
,
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
A T Lu
- Function : Author
- PersonId : 1277568
- ORCID : 0000-0002-2866-7961
Z Fei
- Function : Author
A Haghani
- Function : Author
- PersonId : 1277564
- ORCID : 0000-0002-6052-8793
T R Robeck
- Function : Author
J A Zoller
- Function : Author
- PersonId : 816617
- ORCID : 0000-0001-6309-0291
C Z Li
- Function : Author
- PersonId : 1277565
- ORCID : 0000-0002-3907-7983
R Lowe
- Function : Author
Q Yan
- Function : Author
J Zhang
- Function : Author
- PersonId : 1277567
- ORCID : 0000-0002-4488-1175
H Vu
- Function : Author
J Ablaeva
- Function : Author
V A Acosta-Rodriguez
- Function : Author
- PersonId : 1277570
- ORCID : 0000-0002-4818-0667
D M Adams
- Function : Author
- PersonId : 1277571
- ORCID : 0000-0002-8260-4064
J Almunia
- Function : Author
- PersonId : 1277572
- ORCID : 0000-0001-6343-1463
A Aloysius
- Function : Author
- PersonId : 1277573
- ORCID : 0000-0001-6705-4810
R Ardehali
- Function : Author
A Arneson
- Function : Author
C S Baker
- Function : Author
- PersonId : 1277577
- ORCID : 0000-0003-2183-2036
G Banks
- Function : Author
K Belov
- Function : Author
N C Bennett
- Function : Author
P Black
- Function : Author
D T Blumstein
- Function : Author
- PersonId : 1267949
- ORCID : 0000-0001-5793-9244
E K Bors
- Function : Author
C E Breeze
- Function : Author
- PersonId : 1277583
- ORCID : 0000-0002-5294-915X
R T Brooke
- Function : Author
J L Brown
- Function : Author
G G Carter
- Function : Author
A Caulton
- Function : Author
J M Cavin
- Function : Author
L Chakrabarti
- Function : Author
I Chatzistamou
- Function : Author
H Chen
- Function : Author
K Cheng
- Function : Author
P Chiavellini
- Function : Author
O W Choi
- Function : Author
S M Clarke
- Function : Author
- PersonId : 1277593
- ORCID : 0000-0002-4615-8917
L N Cooper
- Function : Author
- PersonId : 1284311
- ORCID : 0000-0002-1765-927X
M L Cossette
- Function : Author
- PersonId : 1277595
- ORCID : 0000-0001-7215-0997
J Day
- Function : Author
- PersonId : 799399
- ORCID : 0000-0001-9390-7506
J Deyoung
- Function : Author
S Dirocco
- Function : Author
C Dold
- Function : Author
E E Ehmke
- Function : Author
C K Emmons
- Function : Author
- PersonId : 1277600
- ORCID : 0000-0003-1326-3646
S Emmrich
- Function : Author
- PersonId : 1277601
- ORCID : 0000-0002-0537-4242
E Erbay
- Function : Author
C Erlacher-Reid
- Function : Author
C G Faulkes
- Function : Author
- PersonId : 1284312
- ORCID : 0000-0002-5228-9075
S H Ferguson
- Function : Author
- PersonId : 1277605
- ORCID : 0000-0002-3794-0122
C J Finno
- Function : Author
J E Flower
- Function : Author
J M Gaillard
- Function : Author
E Garde
- Function : Author
L Gerber
- Function : Author
V N Gladyshev
- Function : Author
- PersonId : 1277609
- ORCID : 0000-0002-0372-7016
V Gorbunova
- Function : Author
- PersonId : 795657
- ORCID : 0000-0001-8979-0333
R G Goya
- Function : Author
- PersonId : 1277610
- ORCID : 0000-0002-5469-5499
M J Grant
- Function : Author
C B Green
- Function : Author
E N Hales
- Function : Author
M B Hanson
- Function : Author
D W Hart
- Function : Author
- PersonId : 1277614
- ORCID : 0000-0002-4592-558X
M Haulena
- Function : Author
K Herrick
- Function : Author
A N Hogan
- Function : Author
C J Hogg
- Function : Author
- PersonId : 1277616
- ORCID : 0000-0002-6328-398X
T A Hore
- Function : Author
- PersonId : 1277617
- ORCID : 0000-0002-6735-225X
T Huang
- Function : Author
- PersonId : 1277618
- ORCID : 0000-0001-6601-6687
J C Izpisua Belmonte
- Function : Author
A J Jasinska
- Function : Author
- PersonId : 1277619
- ORCID : 0000-0002-1897-4570
G Jones
- Function : Author
- PersonId : 1277620
- ORCID : 0000-0002-1904-3735
E Jourdain
- Function : Author
O Kashpur
- Function : Author
H Katcher
- Function : Author
E Katsumata
- Function : Author
V Kaza
- Function : Author
H Kiaris
- Function : Author
- PersonId : 1277622
- ORCID : 0000-0002-8999-8289
M S Kobor
- Function : Author
P Kordowitzki
- Function : Author
- PersonId : 1277623
- ORCID : 0000-0002-3344-5060
W R Koski
- Function : Author
- PersonId : 1277624
- ORCID : 0000-0001-7426-9975
M Krützen
- Function : Author
- PersonId : 1277625
- ORCID : 0000-0003-1055-5299
S B Kwon
- Function : Author
B Larison
- Function : Author
S G Lee
- Function : Author
M Lehmann
- Function : Author
Jean-François Lemaître Lemaître
- Function : Author
- PersonId : 21692
- IdHAL : jean-francois-lemaitre
- ORCID : 0000-0001-9898-2353
- IdRef : 199291675
A J Levine
- Function : Author
C Li
- Function : Author
X Li
- Function : Author
A R Lim
- Function : Author
D T S Lin
- Function : Author
D M Lindemann
- Function : Author
T J Little
- Function : Author
N Macoretta
- Function : Author
D Maddox
- Function : Author
C O Matkin
- Function : Author
J A Mattison
- Function : Author
M Mcclure
- Function : Author
J Mergl
- Function : Author
J J Meudt
- Function : Author
G A Montano
- Function : Author
K Mozhui
- Function : Author
- PersonId : 1277638
- ORCID : 0000-0002-6623-4112
J Munshi-South
- Function : Author
A Naderi
- Function : Author
- PersonId : 1277640
- ORCID : 0000-0001-9911-5841
M Nagy
- Function : Author
- PersonId : 1277641
- ORCID : 0000-0002-9768-3930
P Narayan
- Function : Author
- PersonId : 1277642
- ORCID : 0000-0002-8713-1470
P W Nathanielsz
- Function : Author
N B Nguyen
- Function : Author
C Niehrs
- Function : Author
J K O’brien
- Function : Author
P O’tierney Ginn
- Function : Author
- PersonId : 1277647
- ORCID : 0000-0001-5752-4874
D T Odom
- Function : Author
A G Ophir
- Function : Author
- PersonId : 1277648
- ORCID : 0000-0002-4877-9696
S Osborn
- Function : Author
E A Ostrander
- Function : Author
- PersonId : 1277649
- ORCID : 0000-0001-6075-9738
K M Parsons
- Function : Author
K C Paul
- Function : Author
M Pellegrini
- Function : Author
K J Peters
- Function : Author
- PersonId : 1277654
- ORCID : 0000-0002-5967-0928
A B Pedersen
- Function : Author
J L Petersen
- Function : Author
- PersonId : 1277655
- ORCID : 0000-0001-5438-8555
D W Pietersen
- Function : Author
- PersonId : 809644
- ORCID : 0000-0002-7592-8319
G M Pinho
- Function : Author
- PersonId : 1277656
- ORCID : 0000-0003-4671-8221
J Plassais
- Function : Author
- PersonId : 1277657
- ORCID : 0000-0002-2112-1595
J R Poganik
- Function : Author
- PersonId : 1277658
- ORCID : 0000-0003-3098-8550
N A Prado
- Function : Author
P Reddy
- Function : Author
B Rey
- Function : Author
- PersonId : 21680
- IdHAL : benjamin-rey
- ORCID : 0000-0002-0464-5573
- IdRef : 189523506
B R Ritz
- Function : Author
- PersonId : 1277661
- ORCID : 0000-0001-6976-7339
J Robbins
- Function : Author
- PersonId : 1277662
- ORCID : 0000-0002-6382-722X
M Rodriguez
- Function : Author
J Russell
- Function : Author
- PersonId : 1277664
- ORCID : 0000-0003-0288-8392
E Rydkina
- Function : Author
L L Sailer
- Function : Author
- PersonId : 1277665
- ORCID : 0000-0003-2020-2390
A B Salmon
- Function : Author
- PersonId : 1277666
- ORCID : 0000-0002-1475-7843
A Sanghavi
- Function : Author
- PersonId : 1277667
- ORCID : 0000-0002-0219-0376
K M Schachtschneider
- Function : Author
D Schmitt
- Function : Author
- PersonId : 1277669
- ORCID : 0000-0003-0023-5427
T Schmitt
- Function : Author
L Schomacher
- Function : Author
- PersonId : 1277671
- ORCID : 0000-0002-3841-5258
L B Schook
- Function : Author
- PersonId : 1284313
- ORCID : 0000-0002-6580-8364
K E Sears
- Function : Author
- PersonId : 1260157
- ORCID : 0000-0001-9744-9602
A W Seifert
- Function : Author
A Seluanov
- Function : Author
- PersonId : 1277703
- ORCID : 0000-0003-3400-538X
A B A Shafer
- Function : Author
D Shanmuganayagam
- Function : Author
- PersonId : 1284314
- ORCID : 0000-0002-8882-1668
A V Shindyapina
- Function : Author
M Simmons
- Function : Author
K Singh
- Function : Author
I Sinha
- Function : Author
J Slone
- Function : Author
R G Snell
- Function : Author
- PersonId : 1277678
- ORCID : 0000-0002-8166-4014
E Soltanmaohammadi
- Function : Author
M L Spangler
- Function : Author
- PersonId : 1277680
- ORCID : 0000-0001-5184-501X
M C Spriggs
- Function : Author
L Staggs
- Function : Author
N Stedman
- Function : Author
K J Steinman
- Function : Author
D T Stewart
- Function : Author
V J Sugrue
- Function : Author
B Szladovits
- Function : Author
- PersonId : 1277685
- ORCID : 0000-0002-1926-3455
J S Takahashi
- Function : Author
- PersonId : 1277686
- ORCID : 0000-0003-0384-8878
M Takasugi
- Function : Author
E C Teeling
- Function : Author
- PersonId : 1277687
- ORCID : 0000-0002-3309-1346
M J Thompson
- Function : Author
- PersonId : 1277688
- ORCID : 0000-0002-2914-1080
B van Bonn
- Function : Author
S C Vernes
- Function : Author
D Villar
- Function : Author
- PersonId : 1232097
- ORCID : 0000-0002-8614-6232
H V Vinters
- Function : Author
M C Wallingford
- Function : Author
N Wang
- Function : Author
R K Wayne
- Function : Author
G S Wilkinson
- Function : Author
- PersonId : 1277693
- ORCID : 0000-0001-7799-8444
C K Williams
- Function : Author
R W Williams
- Function : Author
X W Yang
- Function : Author
- PersonId : 1277704
- ORCID : 0000-0003-3705-7935
M Yao
- Function : Author
B G Young
- Function : Author
- PersonId : 1277696
- ORCID : 0000-0001-7708-3981
B Zhang
- Function : Author
Z Zhang
- Function : Author
P Zhao
- Function : Author
- PersonId : 1277700
- ORCID : 0000-0002-6610-6217
Y Zhao
- Function : Author
W Zhou
- Function : Author
J Zimmermann
- Function : Author
- PersonId : 1284315
- ORCID : 0000-0002-7667-5616
J Ernst
- Function : Author
- PersonId : 1277702
- ORCID : 0000-0003-4026-7853
K Raj
- Function : Author
- PersonId : 1277705
- ORCID : 0000-0002-3744-265X
S Horvath
- Function : Author
- PersonId : 1277706
- ORCID : 0000-0002-4110-3589
Abstract
Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.
Origin : Publisher files allowed on an open archive