Reversing age: Dual species measurement of epigenetic age with a single clock

Autores
Horvath, Steve; Singh, Kavita; Raj, Ken; Khairnar, Shraddha; Sanghav, Akshay; Shrivastava, Agnivesh; Zoller, Joseph A.; Li, Caesar Z.; Hereñú, Claudia Beatriz; Canatelli Mallat, Martina; Lehmann, Marianne; Solberg Woods, Leah C.; Garcia Martinez, Angel; Wang, Tengfei; Chiavellini, Priscila; Levine, Andrew J.; Chen, Hao; Goya, Rodolfo Gustavo; Katcher, Harold L.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.
Fil: Horvath, Steve. University of California at Los Angeles; Estados Unidos
Fil: Singh, Kavita. NMIMS University; India
Fil: Raj, Ken. Public Health England; Reino Unido
Fil: Khairnar, Shraddha. NMIMS University; India
Fil: Sanghav, Akshay. Nugenics Research Pvt Ltd; India
Fil: Shrivastava, Agnivesh. Nugenics Research Pvt Ltd; India
Fil: Zoller, Joseph A.. University of California at Los Angeles; Estados Unidos
Fil: Li, Caesar Z.. University of California at Los Angeles; Estados Unidos
Fil: Hereñú, Claudia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
Fil: Canatelli Mallat, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Lehmann, Marianne. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Solberg Woods, Leah C.. Wake Forest University School of Medicine; Estados Unidos
Fil: Garcia Martinez, Angel. University of Tennessee; Estados Unidos
Fil: Wang, Tengfei. University of Tennessee; Estados Unidos
Fil: Chiavellini, Priscila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Levine, Andrew J.. University of California at Los Angeles; Estados Unidos
Fil: Chen, Hao. University of Tennessee; Estados Unidos
Fil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Katcher, Harold L.. Nugenics Research Pvt Ltd; India
Materia
REJUVENATION
PLASMA FRACTION
EPIGENETIC CLOCK
DNA METHYLATION
RAT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/181307
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Reversing age: Dual species measurement of epigenetic age with a single clockHorvath, SteveSingh, KavitaRaj, KenKhairnar, ShraddhaSanghav, AkshayShrivastava, AgniveshZoller, Joseph A.Li, Caesar Z.Hereñú, Claudia BeatrizCanatelli Mallat, MartinaLehmann, MarianneSolberg Woods, Leah C.Garcia Martinez, AngelWang, TengfeiChiavellini, PriscilaLevine, Andrew J.Chen, HaoGoya, Rodolfo GustavoKatcher, Harold L.REJUVENATIONPLASMA FRACTIONEPIGENETIC CLOCKDNA METHYLATIONRAThttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.Fil: Horvath, Steve. University of California at Los Angeles; Estados UnidosFil: Singh, Kavita. NMIMS University; IndiaFil: Raj, Ken. Public Health England; Reino UnidoFil: Khairnar, Shraddha. NMIMS University; IndiaFil: Sanghav, Akshay. Nugenics Research Pvt Ltd; IndiaFil: Shrivastava, Agnivesh. Nugenics Research Pvt Ltd; IndiaFil: Zoller, Joseph A.. University of California at Los Angeles; Estados UnidosFil: Li, Caesar Z.. University of California at Los Angeles; Estados UnidosFil: Hereñú, Claudia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Canatelli Mallat, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Lehmann, Marianne. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Solberg Woods, Leah C.. Wake Forest University School of Medicine; Estados UnidosFil: Garcia Martinez, Angel. University of Tennessee; Estados UnidosFil: Wang, Tengfei. University of Tennessee; Estados UnidosFil: Chiavellini, Priscila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Levine, Andrew J.. University of California at Los Angeles; Estados UnidosFil: Chen, Hao. University of Tennessee; Estados UnidosFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Katcher, Harold L.. Nugenics Research Pvt Ltd; IndiaCold Spring Harbor Laboratory Press2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/181307Horvath, Steve; Singh, Kavita; Raj, Ken; Khairnar, Shraddha; Sanghav, Akshay; et al.; Reversing age: Dual species measurement of epigenetic age with a single clock; Cold Spring Harbor Laboratory Press; BiorXiv; 5-2020; 1-302692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1101/2020.05.07.082917info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:06:27Zoai:ri.conicet.gov.ar:11336/181307instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:06:27.339CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reversing age: Dual species measurement of epigenetic age with a single clock
title Reversing age: Dual species measurement of epigenetic age with a single clock
spellingShingle Reversing age: Dual species measurement of epigenetic age with a single clock
Horvath, Steve
REJUVENATION
PLASMA FRACTION
EPIGENETIC CLOCK
DNA METHYLATION
RAT
title_short Reversing age: Dual species measurement of epigenetic age with a single clock
title_full Reversing age: Dual species measurement of epigenetic age with a single clock
title_fullStr Reversing age: Dual species measurement of epigenetic age with a single clock
title_full_unstemmed Reversing age: Dual species measurement of epigenetic age with a single clock
title_sort Reversing age: Dual species measurement of epigenetic age with a single clock
dc.creator.none.fl_str_mv Horvath, Steve
Singh, Kavita
Raj, Ken
Khairnar, Shraddha
Sanghav, Akshay
Shrivastava, Agnivesh
Zoller, Joseph A.
Li, Caesar Z.
Hereñú, Claudia Beatriz
Canatelli Mallat, Martina
Lehmann, Marianne
Solberg Woods, Leah C.
Garcia Martinez, Angel
Wang, Tengfei
Chiavellini, Priscila
Levine, Andrew J.
Chen, Hao
Goya, Rodolfo Gustavo
Katcher, Harold L.
author Horvath, Steve
author_facet Horvath, Steve
Singh, Kavita
Raj, Ken
Khairnar, Shraddha
Sanghav, Akshay
Shrivastava, Agnivesh
Zoller, Joseph A.
Li, Caesar Z.
Hereñú, Claudia Beatriz
Canatelli Mallat, Martina
Lehmann, Marianne
Solberg Woods, Leah C.
Garcia Martinez, Angel
Wang, Tengfei
Chiavellini, Priscila
Levine, Andrew J.
Chen, Hao
Goya, Rodolfo Gustavo
Katcher, Harold L.
author_role author
author2 Singh, Kavita
Raj, Ken
Khairnar, Shraddha
Sanghav, Akshay
Shrivastava, Agnivesh
Zoller, Joseph A.
Li, Caesar Z.
Hereñú, Claudia Beatriz
Canatelli Mallat, Martina
Lehmann, Marianne
Solberg Woods, Leah C.
Garcia Martinez, Angel
Wang, Tengfei
Chiavellini, Priscila
Levine, Andrew J.
Chen, Hao
Goya, Rodolfo Gustavo
Katcher, Harold L.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv REJUVENATION
PLASMA FRACTION
EPIGENETIC CLOCK
DNA METHYLATION
RAT
topic REJUVENATION
PLASMA FRACTION
EPIGENETIC CLOCK
DNA METHYLATION
RAT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.
Fil: Horvath, Steve. University of California at Los Angeles; Estados Unidos
Fil: Singh, Kavita. NMIMS University; India
Fil: Raj, Ken. Public Health England; Reino Unido
Fil: Khairnar, Shraddha. NMIMS University; India
Fil: Sanghav, Akshay. Nugenics Research Pvt Ltd; India
Fil: Shrivastava, Agnivesh. Nugenics Research Pvt Ltd; India
Fil: Zoller, Joseph A.. University of California at Los Angeles; Estados Unidos
Fil: Li, Caesar Z.. University of California at Los Angeles; Estados Unidos
Fil: Hereñú, Claudia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
Fil: Canatelli Mallat, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Lehmann, Marianne. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Solberg Woods, Leah C.. Wake Forest University School of Medicine; Estados Unidos
Fil: Garcia Martinez, Angel. University of Tennessee; Estados Unidos
Fil: Wang, Tengfei. University of Tennessee; Estados Unidos
Fil: Chiavellini, Priscila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Levine, Andrew J.. University of California at Los Angeles; Estados Unidos
Fil: Chen, Hao. University of Tennessee; Estados Unidos
Fil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Katcher, Harold L.. Nugenics Research Pvt Ltd; India
description Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.
publishDate 2020
dc.date.none.fl_str_mv 2020-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/181307
Horvath, Steve; Singh, Kavita; Raj, Ken; Khairnar, Shraddha; Sanghav, Akshay; et al.; Reversing age: Dual species measurement of epigenetic age with a single clock; Cold Spring Harbor Laboratory Press; BiorXiv; 5-2020; 1-30
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/181307
identifier_str_mv Horvath, Steve; Singh, Kavita; Raj, Ken; Khairnar, Shraddha; Sanghav, Akshay; et al.; Reversing age: Dual species measurement of epigenetic age with a single clock; Cold Spring Harbor Laboratory Press; BiorXiv; 5-2020; 1-30
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1101/2020.05.07.082917
info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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