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 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.
Subject(s)
Aging , Epigenesis, Genetic , Humans , Rats , Mice , Animals , Swine , Aging/physiology , Biomarkers , Plasma , Immunoglobulin GABSTRACT
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.
ABSTRACT
Power analyses are often used to determine the number of animals required for a genome-wide association study (GWAS). These analyses are typically intended to estimate the sample size needed for at least 1 locus to exceed a genome-wide significance threshold. A related question that is less commonly considered is the number of significant loci that will be discovered with a given sample size. We used simulations based on a real data set that consisted of 3,173 male and female adult N/NIH heterogeneous stock rats to explore the relationship between sample size and the number of significant loci discovered. Our simulations examined the number of loci identified in subsamples of the full data set. The subsampling analysis was conducted for 4 traits with low (0.15 ± 0.03), medium (0.31 ± 0.03 and 0.36 ± 0.03), and high (0.46 ± 0.03) SNP-based heritabilities. For each trait, we subsampled the data 100 times at different sample sizes (500, 1,000, 1,500, 2,000, and 2,500). We observed an exponential increase in the number of significant loci with larger sample sizes. Our results are consistent with similar observations in human GWAS and imply that future rodent GWAS should use sample sizes that are significantly larger than those needed to obtain a single significant result.
Subject(s)
Genome-Wide Association Study , Quantitative Trait Loci , Male , Female , Humans , Animals , Rats , Genome-Wide Association Study/methods , Sample Size , Polymorphism, Single Nucleotide , PhenotypeABSTRACT
Congenital diaphragmatic hernia incidence is one in 3000 live births, Bochdalek hernia occurs through a posterolateral defect. It is very rare in adults. We present a case of late relapsed one diagnosed in an adult male. He underwent an open intervention of Bochdalek hernia at first day of life and required reintervention at seventh month due to recurrence. Now, computerized tomography scan demonstrates a right diaphragmatic defect with intrathoracic hydronephrotic kidney. Nephrectomy was performed with Video-assisted Thoracic Surgery using laparoscopic ports and material. The diaphragmatic defect was closed with a polypropylene mesh. The patient was discharged after 72 h. (AU)
La incidencia de hernia diafragmática congénita es de uno en 3000 nacidos vivos, la hernia de Bochdalek ocurre a través de un defecto diafragmático posterolateral. Es muy raro en adultos. Presentamos un caso de recidiva tardía diagnosticada en un varón adulto. Se sometió a una intervención abierta de hernia de Bochdalek el primer día de vida y requirió reintervención por recurrencia al séptimo mes. La tomografía computarizada actual demuestra un defecto diafragmático derecho con riñón hidronefrótico intratorácico. Se realizó nefrectomía mediante cirugía torácica vídeo-asistida utilizando puertos y material laparoscópicos. El defecto diafragmático se cerró con una malla de polipropileno. El paciente fue dado de alta a las 72 horas de la intervención.La incidencia de hernia diafragmática congénita es de uno en 3000 nacidos vivos, la hernia de Bochdalek ocurre a través de un defecto diafragmático posterolateral. Es muy raro en adultos. Presentamos un caso de recidiva tardía diagnosticada en un varón adulto. Se sometió a una intervención abierta de hernia de Bochdalek el primer día de vida y requirió reintervención por recurrencia al séptimo mes. La tomografía computarizada actual demuestra un defecto diafragmático derecho con riñón hidronefrótico intratorácico. Se realizó nefrectomía mediante cirugía torácica vídeo-asistida utilizando puertos y material laparoscópicos. El defecto diafragmático se cerró con una malla de polipropileno. El paciente fue dado de alta a las 72 horas de la intervención. (AU)
