Reversal of biological age in multiple rat organs by young porcine plasma fraction
- Autores
- Horvath, Steve; Singh, Kavita; Raj, Ken; Khairnar, Shraddha I.; Sanghavi, Akshay; Shrivastava, Agnivesh; Zoller, Joseph A.; Li, Caesar Z.; Hereñú, Claudia Beatriz; Canatelli Mallat, Martina; Lehmann, Marianne; Habazin, Sinisa; Novokmet, Mislav; Vuckovic, Frano; Solberg Woods, Leah C.; García Martínez, Ángel; Wang, Tengfei; Chiavellini, Priscila; Levine, Andrew J.; Chen, Hao; Brooke, Robert T.; Gordevicius, Juozas; Lauc, Gordan; Goya, Rodolfo Gustavo; Katcher, Harold L.
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young adult pigs rejuvenates old rat 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 = 613 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 = 1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine 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, behavioral responses encompassing cognitive functions. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging.
Fil: Horvath, Steve. Ucla Fielding School Of Public Health; Estados Unidos. Altos Labs; Reino Unido. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Singh, Kavita. Narsee Monjee Institute Of Management Studies, Mumbai; India
Fil: Raj, Ken. Altos Labs; Reino Unido
Fil: Khairnar, Shraddha I.. Narsee Monjee Institute Of Management Studies, Mumbai; India
Fil: Sanghavi, Akshay. Yuvan Research; Estados Unidos
Fil: Shrivastava, Agnivesh. Yuvan Research; Estados Unidos
Fil: Zoller, Joseph A.. Ucla Fielding School Of Public Health; Estados Unidos
Fil: Li, Caesar Z.. Ucla Fielding School Of Public Health; Estados Unidos
Fil: Hereñú, Claudia Beatriz. Universidad Nacional de Córdoba; Argentina. 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. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Habazin, Sinisa. Genos Glycoscience Research Laboratory; Croacia
Fil: Novokmet, Mislav. Genos Glycoscience Research Laboratory; Croacia
Fil: Vuckovic, Frano. Genos Glycoscience Research Laboratory; Croacia
Fil: Solberg Woods, Leah C.. Wake Forest University School Of Medicine; Estados Unidos
Fil: García Martínez, Ángel. University of Tennessee; Estados Unidos
Fil: Wang, Tengfei. University of Tennessee; Estados Unidos
Fil: Chiavellini, Priscila. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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. School of Medicine; Estados Unidos
Fil: Chen, Hao. University of Tennessee; Estados Unidos
Fil: Brooke, Robert T.. Epigenetic Clock Development Foundation; Estados Unidos
Fil: Gordevicius, Juozas. Epigenetic Clock Development Foundation; Estados Unidos
Fil: Lauc, Gordan. Genos Glycoscience Research Laboratory; Croacia
Fil: Goya, Rodolfo Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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.. Yuvan Research; Estados Unidos - Materia
-
DNA METHYLATION
EPIGENETIC CLOCK
GLYCANS
PLASMA FRACTION
RAT
REJUVENATION - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/230824
Ver los metadatos del registro completo
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Reversal of biological age in multiple rat organs by young porcine plasma fractionHorvath, SteveSingh, KavitaRaj, KenKhairnar, Shraddha I.Sanghavi, AkshayShrivastava, AgniveshZoller, Joseph A.Li, Caesar Z.Hereñú, Claudia BeatrizCanatelli Mallat, MartinaLehmann, MarianneHabazin, SinisaNovokmet, MislavVuckovic, FranoSolberg Woods, Leah C.García Martínez, ÁngelWang, TengfeiChiavellini, PriscilaLevine, Andrew J.Chen, HaoBrooke, Robert T.Gordevicius, JuozasLauc, GordanGoya, Rodolfo GustavoKatcher, Harold L.DNA METHYLATIONEPIGENETIC CLOCKGLYCANSPLASMA FRACTIONRATREJUVENATIONhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young adult pigs rejuvenates old rat 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 = 613 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 = 1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine 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, behavioral responses encompassing cognitive functions. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging.Fil: Horvath, Steve. Ucla Fielding School Of Public Health; Estados Unidos. Altos Labs; Reino Unido. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Singh, Kavita. Narsee Monjee Institute Of Management Studies, Mumbai; IndiaFil: Raj, Ken. Altos Labs; Reino UnidoFil: Khairnar, Shraddha I.. Narsee Monjee Institute Of Management Studies, Mumbai; IndiaFil: Sanghavi, Akshay. Yuvan Research; Estados UnidosFil: Shrivastava, Agnivesh. Yuvan Research; Estados UnidosFil: Zoller, Joseph A.. Ucla Fielding School Of Public Health; Estados UnidosFil: Li, Caesar Z.. Ucla Fielding School Of Public Health; Estados UnidosFil: Hereñú, Claudia Beatriz. Universidad Nacional de Córdoba; Argentina. 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. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Habazin, Sinisa. Genos Glycoscience Research Laboratory; CroaciaFil: Novokmet, Mislav. Genos Glycoscience Research Laboratory; CroaciaFil: Vuckovic, Frano. Genos Glycoscience Research Laboratory; CroaciaFil: Solberg Woods, Leah C.. Wake Forest University School Of Medicine; Estados UnidosFil: García Martínez, Ángel. University of Tennessee; Estados UnidosFil: Wang, Tengfei. University of Tennessee; Estados UnidosFil: Chiavellini, Priscila. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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. School of Medicine; Estados UnidosFil: Chen, Hao. University of Tennessee; Estados UnidosFil: Brooke, Robert T.. Epigenetic Clock Development Foundation; Estados UnidosFil: Gordevicius, Juozas. Epigenetic Clock Development Foundation; Estados UnidosFil: Lauc, Gordan. Genos Glycoscience Research Laboratory; CroaciaFil: Goya, Rodolfo Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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.. Yuvan Research; Estados UnidosSpringer Science and Business Media Deutschland GmbH2023-10-24info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230824Horvath, Steve; Singh, Kavita; Raj, Ken; Khairnar, Shraddha I.; Sanghavi, Akshay; et al.; Reversal of biological age in multiple rat organs by young porcine plasma fraction; Springer Science and Business Media Deutschland GmbH; GeroScience; 46; 24-10-2023; 367-3942509-27152509-2723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s11357-023-00980-6info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s11357-023-00980-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:08Zoai:ri.conicet.gov.ar:11336/230824instacron: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:34982025-09-03 10:05:08.35CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Reversal of biological age in multiple rat organs by young porcine plasma fraction |
| title |
Reversal of biological age in multiple rat organs by young porcine plasma fraction |
| spellingShingle |
Reversal of biological age in multiple rat organs by young porcine plasma fraction Horvath, Steve DNA METHYLATION EPIGENETIC CLOCK GLYCANS PLASMA FRACTION RAT REJUVENATION |
| title_short |
Reversal of biological age in multiple rat organs by young porcine plasma fraction |
| title_full |
Reversal of biological age in multiple rat organs by young porcine plasma fraction |
| title_fullStr |
Reversal of biological age in multiple rat organs by young porcine plasma fraction |
| title_full_unstemmed |
Reversal of biological age in multiple rat organs by young porcine plasma fraction |
| title_sort |
Reversal of biological age in multiple rat organs by young porcine plasma fraction |
| dc.creator.none.fl_str_mv |
Horvath, Steve Singh, Kavita Raj, Ken Khairnar, Shraddha I. Sanghavi, Akshay Shrivastava, Agnivesh Zoller, Joseph A. Li, Caesar Z. Hereñú, Claudia Beatriz Canatelli Mallat, Martina Lehmann, Marianne Habazin, Sinisa Novokmet, Mislav Vuckovic, Frano Solberg Woods, Leah C. García Martínez, Ángel Wang, Tengfei Chiavellini, Priscila Levine, Andrew J. Chen, Hao Brooke, Robert T. Gordevicius, Juozas Lauc, Gordan Goya, Rodolfo Gustavo Katcher, Harold L. |
| author |
Horvath, Steve |
| author_facet |
Horvath, Steve Singh, Kavita Raj, Ken Khairnar, Shraddha I. Sanghavi, Akshay Shrivastava, Agnivesh Zoller, Joseph A. Li, Caesar Z. Hereñú, Claudia Beatriz Canatelli Mallat, Martina Lehmann, Marianne Habazin, Sinisa Novokmet, Mislav Vuckovic, Frano Solberg Woods, Leah C. García Martínez, Ángel Wang, Tengfei Chiavellini, Priscila Levine, Andrew J. Chen, Hao Brooke, Robert T. Gordevicius, Juozas Lauc, Gordan Goya, Rodolfo Gustavo Katcher, Harold L. |
| author_role |
author |
| author2 |
Singh, Kavita Raj, Ken Khairnar, Shraddha I. Sanghavi, Akshay Shrivastava, Agnivesh Zoller, Joseph A. Li, Caesar Z. Hereñú, Claudia Beatriz Canatelli Mallat, Martina Lehmann, Marianne Habazin, Sinisa Novokmet, Mislav Vuckovic, Frano Solberg Woods, Leah C. García Martínez, Ángel Wang, Tengfei Chiavellini, Priscila Levine, Andrew J. Chen, Hao Brooke, Robert T. Gordevicius, Juozas Lauc, Gordan 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 author author author author author author |
| dc.subject.none.fl_str_mv |
DNA METHYLATION EPIGENETIC CLOCK GLYCANS PLASMA FRACTION RAT REJUVENATION |
| topic |
DNA METHYLATION EPIGENETIC CLOCK GLYCANS PLASMA FRACTION RAT REJUVENATION |
| 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 and rats. However, it was not known whether plasma from young adult pigs rejuvenates old rat 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 = 613 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 = 1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine 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, behavioral responses encompassing cognitive functions. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging. Fil: Horvath, Steve. Ucla Fielding School Of Public Health; Estados Unidos. Altos Labs; Reino Unido. University of California at Los Angeles. School of Medicine; Estados Unidos Fil: Singh, Kavita. Narsee Monjee Institute Of Management Studies, Mumbai; India Fil: Raj, Ken. Altos Labs; Reino Unido Fil: Khairnar, Shraddha I.. Narsee Monjee Institute Of Management Studies, Mumbai; India Fil: Sanghavi, Akshay. Yuvan Research; Estados Unidos Fil: Shrivastava, Agnivesh. Yuvan Research; Estados Unidos Fil: Zoller, Joseph A.. Ucla Fielding School Of Public Health; Estados Unidos Fil: Li, Caesar Z.. Ucla Fielding School Of Public Health; Estados Unidos Fil: Hereñú, Claudia Beatriz. Universidad Nacional de Córdoba; Argentina. 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. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina Fil: Habazin, Sinisa. Genos Glycoscience Research Laboratory; Croacia Fil: Novokmet, Mislav. Genos Glycoscience Research Laboratory; Croacia Fil: Vuckovic, Frano. Genos Glycoscience Research Laboratory; Croacia Fil: Solberg Woods, Leah C.. Wake Forest University School Of Medicine; Estados Unidos Fil: García Martínez, Ángel. University of Tennessee; Estados Unidos Fil: Wang, Tengfei. University of Tennessee; Estados Unidos Fil: Chiavellini, Priscila. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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. School of Medicine; Estados Unidos Fil: Chen, Hao. University of Tennessee; Estados Unidos Fil: Brooke, Robert T.. Epigenetic Clock Development Foundation; Estados Unidos Fil: Gordevicius, Juozas. Epigenetic Clock Development Foundation; Estados Unidos Fil: Lauc, Gordan. Genos Glycoscience Research Laboratory; Croacia Fil: Goya, Rodolfo Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. 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.. Yuvan Research; Estados Unidos |
| description |
Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young adult pigs rejuvenates old rat 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 = 613 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 = 1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine 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, behavioral responses encompassing cognitive functions. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-10-24 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
| status_str |
publishedVersion |
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http://hdl.handle.net/11336/230824 Horvath, Steve; Singh, Kavita; Raj, Ken; Khairnar, Shraddha I.; Sanghavi, Akshay; et al.; Reversal of biological age in multiple rat organs by young porcine plasma fraction; Springer Science and Business Media Deutschland GmbH; GeroScience; 46; 24-10-2023; 367-394 2509-2715 2509-2723 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/230824 |
| identifier_str_mv |
Horvath, Steve; Singh, Kavita; Raj, Ken; Khairnar, Shraddha I.; Sanghavi, Akshay; et al.; Reversal of biological age in multiple rat organs by young porcine plasma fraction; Springer Science and Business Media Deutschland GmbH; GeroScience; 46; 24-10-2023; 367-394 2509-2715 2509-2723 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1007/s11357-023-00980-6 info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s11357-023-00980-6 |
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Springer Science and Business Media Deutschland GmbH |
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Springer Science and Business Media Deutschland GmbH |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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