Reversal of biological age in multiple rat organs by young porcine plasma fraction.

Autor: Horvath S; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.; Altos Labs, Cambridge, UK. shorvath@mednet.ucla.edu., Singh K; Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS University, Mumbai, India., Raj K; Altos Labs, Cambridge, UK., Khairnar SI; Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS University, Mumbai, India., Sanghavi A; Yuvan Research Inc., Mountain View, CA, USA., Shrivastava A; Yuvan Research Inc., Mountain View, CA, USA., Zoller JA; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA., Li CZ; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA., Herenu CB; Institute for Experimental Pharmacology of Cordoba (IFEC), School of Chemical Sciences, National University of Cordoba, Cordoba, Argentina., Canatelli-Mallat M; Biochemistry Research Institute of La Plata-Histology B, Pathology B, School of Medicine, University of La Plata, La Plata, Argentina., Lehmann M; Biochemistry Research Institute of La Plata-Histology B, Pathology B, School of Medicine, University of La Plata, La Plata, Argentina., Habazin S; Genos Glycoscience Research Laboratory, Zagreb, Croatia., Novokmet M; Genos Glycoscience Research Laboratory, Zagreb, Croatia., Vučković F; Genos Glycoscience Research Laboratory, Zagreb, Croatia., Solberg Woods LC; Wake Forest University School of Medicine, Medical Center Drive, Winston Salem, NC, USA., Martinez AG; Department of Pharmacology, Addiction Science and Toxicology, The University of Tennessee Health Science Center, Memphis, TN, USA., Wang T; Department of Pharmacology, Addiction Science and Toxicology, The University of Tennessee Health Science Center, Memphis, TN, USA., Chiavellini P; Biochemistry Research Institute of La Plata-Histology B, Pathology B, School of Medicine, University of La Plata, La Plata, Argentina., Levine AJ; Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA., Chen H; Department of Pharmacology, Addiction Science and Toxicology, The University of Tennessee Health Science Center, Memphis, TN, USA., Brooke RT; Epigenetic Clock Development Foundation, Torrance, CA, USA., Gordevicius J; Epigenetic Clock Development Foundation, Torrance, CA, USA., Lauc G; Genos Glycoscience Research Laboratory, Zagreb, Croatia.; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia., Goya RG; Biochemistry Research Institute of La Plata-Histology B, Pathology B, School of Medicine, University of La Plata, La Plata, Argentina., Katcher HL; Yuvan Research Inc., Mountain View, CA, USA. har.kat@yuvanresearch.com.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Feb; Vol. 46 (1), pp. 367-394. Date of Electronic Publication: 2023 Oct 24.
DOI: 10.1007/s11357-023-00980-6
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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