https://www.biorxiv.org/content/10.1101/2023.08.06.552148v1 Skip to main content bioRxiv * Home * About * Submit * ALERTS / RSS Search for this keyword [ ] [Search] Advanced Search New Results Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction View ORCID ProfileSteve Horvath, Kavita Singh, Ken Raj, Shraddha Khairnar, Akshay Sanghavi, Agnivesh Shrivastava, View ORCID Profile Joseph A. Zoller, Caesar Z. Li, Claudia B. Herenu, Martina Canatelli-Mallat, Marianne Lehmann, Sinisa Habazin, Mislav Novokmet, Frano Vuckovic, Leah C. Solberg Woods, Angel Garcia Martinez, Tengfei Wang, Priscila Chiavellini, Andrew J. Levine, Hao Chen, Robert T Brooke, Juozas Gordevicius, Gordan Lauc, Rodolfo G. Goya, Harold L. Katcher doi: https://doi.org/10.1101/2023.08.06.552148 Steve Horvath 1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; 2Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA; 3Altos Labs, Cambridge, UK; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Steve Horvath * For correspondence: shorvath@mednet.ucla.edu har.kat@yuvanresearch.com Kavita Singh 4Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM'S NMIMS University, Mumbai, India; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Ken Raj 3Altos Labs, Cambridge, UK; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Shraddha Khairnar 4Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM'S NMIMS University, Mumbai, India; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Akshay Sanghavi 5Yuvan Research Inc, Mountain View, CA, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Agnivesh Shrivastava 5Yuvan Research Inc, Mountain View, CA, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Joseph A. Zoller 2Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Joseph A. Zoller Caesar Z. Li 2Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Claudia B. Herenu 6Institute for Experimental Pharmacology of Cordoba (IFEC), School of Chemical Sciences, National University of Cordoba, Cordoba, Argentina ; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Martina Canatelli-Mallat 7Biochemistry Research Institute of La Plata - Histology B, Pathology B, School of Medicine, University of La Plata, La Plata CC 455 (zip 1900), Argentina; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Marianne Lehmann 7Biochemistry Research Institute of La Plata - Histology B, Pathology B, School of Medicine, University of La Plata, La Plata CC 455 (zip 1900), Argentina; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Sinisa Habazin 8Genos Glycoscience Research Laboratory, Zagreb, Croatia * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Mislav Novokmet 8Genos Glycoscience Research Laboratory, Zagreb, Croatia * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Frano Vuckovic 8Genos Glycoscience Research Laboratory, Zagreb, Croatia * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Leah C. Solberg Woods 9Wake Forest University School of Medicine, 1 Medical Center Drive, Winston Salem, NC 27157, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Angel Garcia Martinez 10Department of Pharmacology, Addiction Science and Toxicology, The University of Tennessee Health Science Center, Memphis, TN 3993, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Tengfei Wang 10Department of Pharmacology, Addiction Science and Toxicology, The University of Tennessee Health Science Center, Memphis, TN 3993, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Priscila Chiavellini 7Biochemistry Research Institute of La Plata - Histology B, Pathology B, School of Medicine, University of La Plata, La Plata CC 455 (zip 1900), Argentina; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Andrew J. Levine 11Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, 90095, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Hao Chen 10Department of Pharmacology, Addiction Science and Toxicology, The University of Tennessee Health Science Center, Memphis, TN 3993, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Robert T Brooke 12Epigenetic Clock Development Foundation, Torrance, California, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Juozas Gordevicius 12Epigenetic Clock Development Foundation, Torrance, California, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Gordan Lauc 8Genos Glycoscience Research Laboratory, Zagreb, Croatia 13Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Rodolfo G. Goya 7Biochemistry Research Institute of La Plata - Histology B, Pathology B, School of Medicine, University of La Plata, La Plata CC 455 (zip 1900), Argentina; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Harold L. Katcher 5Yuvan Research Inc, Mountain View, CA, USA; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * For correspondence: shorvath@mednet.ucla.edu har.kat@yuvanresearch.com * Abstract * Full Text * Info/History * Metrics * Supplementary material * Preview PDF Loading ABSTRACT 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 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 and behavioral responses to assess 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. Competing Interest Statement Several authors are founders, owners, employees (Harold Katcher and Akshay Sanghavi) or consultants of Yuvan Research (Steve Horvath and Agnivesh Shrivastava) which plans to commercialize the E5 treatment. Other authors (Kavita Singh, Shraddha Khairnar) received financial support from Yuvan Research. Gordan Lauc is a founder and CEO of Genos Ltd., a company specialized in high throughput glycomics. Sinisa Habazin, Mislav Novokmet and Frano Vuckovic are employees of Genos Ltd. The other authors do not have conflict of interest. Footnotes * |# Joint first authorship 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 4.0 International license. View the discussion thread. Back to top PreviousNext Posted August 07, 2023. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * [ ] Your Name * [ ] Send To * [ ] [ ] [ ] [ ] [ ] Enter multiple addresses on separate lines or separate them with commas. 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Katcher bioRxiv 2023.08.06.552148; doi: https://doi.org/10.1101/ 2023.08.06.552148 Share This Article: [https://www.biorxiv.org/content/10.1101/2023.08.06] Copy Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo Citation Tools Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction Steve Horvath, Kavita Singh, Ken Raj, Shraddha Khairnar, Akshay Sanghavi, Agnivesh Shrivastava, Joseph A. Zoller, Caesar Z. Li, Claudia B. Herenu, Martina Canatelli-Mallat, Marianne Lehmann, Sinisa Habazin, Mislav Novokmet, Frano Vuckovic, Leah C. Solberg Woods, Angel Garcia Martinez, Tengfei Wang, Priscila Chiavellini, Andrew J. Levine, Hao Chen, Robert T Brooke, Juozas Gordevicius, Gordan Lauc, Rodolfo G. Goya, Harold L. 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