RESUMEN
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.
Asunto(s)
Envejecimiento , Epigénesis Genética , Humanos , Ratas , Ratones , Animales , Porcinos , Envejecimiento/fisiología , Biomarcadores , Plasma , Inmunoglobulina GRESUMEN
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.
RESUMEN
Our group at Yuvan Research has conducted several experiments in recent years that have demonstrated the reversibility of aging through the use of a young plasma fraction, following a historical line of research that began with heterochronic parabiosis. However, a one-of-a-kind discovery, in the form of anecdotal evidence, has recently clarified many doubts about the nature of aging and rejuvenation, and the conclusions that can be drawn from this discovery allow us to form a relatively clear picture of the mechanics of the aging and rejuvenation processes.
RESUMEN
The modern synthesis or evolutionary theory of aging assumes that aging results from the accumulation of errors or damages at the cellular level through the inadequacies of an organism's repair and maintenance machinery. The demonstration of cellular and organic rejuvenation requires the hypothesis that aging is the result of irreparable damage to be rejected. I will propose basic principles of mammalian aging based only on experimental data, without imposing the constraints of evolutionary theory. Consideration of the results of experiment suggests that fundamental assumptions about cell and organ aging being autonomous process, and about the centrality of cellular aging in organismic aging are wrong. The derived principles indicate that exogenous control of age-phenotype at cellular and higher levels of biological organization is possible.
Asunto(s)
Envejecimiento , Senescencia Celular , Animales , Evolución Biológica , Humanos , Modelos Biológicos , FenotipoRESUMEN
The modern synthesis or evolutionary theory of aging assumes that aging results from the accumulation of errors or damages at the cellular level through the inadequacies of an organism's repair and maintenance machinery. The demonstration of cellular and organic rejuvenation requires the hypothesis that aging is the result of irreparable damage to be rejected. I will propose basic principles of mammalian aging based only on experimental data, without imposing the constraints of evolutionary theory. Consideration of the results of experiment suggests that fundamental assumptions about cell and organ aging being autonomous process, and about the centrality of cellular aging in organismic aging are wrong. The derived principles indicate that exogenous control of age-phenotype at cellular and higher levels of biological organization is possible.
