The offspring have suggested that environmental stressors can predispose offspring to various metabolicAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptAnn N Y Acad Sci. Author manuscript; available in PMC 2016 July 01.Wahlqvist et al.Pagesyndromes.13,14 A role for paternal RNAs in the epigenetic transgenerational inheritance of these traits has been proposed. While this seems rather unusual, Krawetz observed, one could view this process as the organism “testing” a response before fixation within the genome. Also unanswered is how such testing is achieved, Procyanidin B1 cancer considering that a signal has to be transmitted–in this case RNAs–from the target to the testis and perhaps back. This has fueled speculation that, perhaps, signaling is mediated by exosomes.15 Krawetz summarized by saying that sperm are not just transporters of genomes, but also contributors of other essential genetic, epigenetic, and non-genetic information to offspring. Transgenerational response to nutrition, early-life circumstances, and longevity Nico S. Rizzo (Loma Linda University and Karolinska Institute) discussed recent developments in research of epigenetics and transgenerational responses to nutrition and early-life circumstances, which may identify novel pathways providing insight into the pathogenesis of chronic diseases.16,17 While the sequencing and detailed mapping of the genome is essential for a basic understanding of DNA, knowing the mechanisms required for expressing the complex genetic information is essential for understanding the manifestation or repression of disease patterns. Epigenetics–a relatively young field–describes the mitotically heritable state of gene Pyrvinium pamoate price expression potential, enabled by the mechanisms of DNA methylation, histone modification and chromatin marks.18 Epigenetics involves the investigation of both the mechanisms of heritable and non-heritable changes in gene expression that do not involve modifications of the DNA coding sequence.19 The study of inherited and environmentallyacquired epigenetic alterations is important to understand disease etiology and effects of health-altering environmental events across multiple generations.20 Transgenerational epigenetic research, continued Rizzo, focuses on measurable outcomes in the offspring generation that are related to pre-conception exposures in the parental–or further removed– ancestral generations.17 An inclusive investigation of possible transgenerational epigenetic pathways should take into account social patterning and cultural inheritance in order to disentangle secondary pathways that influence measurable health outcomes in offspring. The socio-cultural context, environment, acquired and transferred health behaviors, and lifestyles of ancestral and offspring generations need to be considered. Figure 2 provides a schematic overview of interactions and pathways that influence adult health and longevity in the offspring generation. Interesting paternal transgenerational effects in humans have been observed in the erkalix cohort in northern Sweden.21,22 Meticulously maintained parish registries in this mainly agricultural region over more than a century recorded fluctuations in crop yields between years of abject famine and excess resulting in differences in longevity and specific causes of death in subsequent generations expressed through the paternal line.17,21 Although these observations were in concordance with expected differences between X versus Y chromoso.The offspring have suggested that environmental stressors can predispose offspring to various metabolicAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptAnn N Y Acad Sci. Author manuscript; available in PMC 2016 July 01.Wahlqvist et al.Pagesyndromes.13,14 A role for paternal RNAs in the epigenetic transgenerational inheritance of these traits has been proposed. While this seems rather unusual, Krawetz observed, one could view this process as the organism “testing” a response before fixation within the genome. Also unanswered is how such testing is achieved, considering that a signal has to be transmitted–in this case RNAs–from the target to the testis and perhaps back. This has fueled speculation that, perhaps, signaling is mediated by exosomes.15 Krawetz summarized by saying that sperm are not just transporters of genomes, but also contributors of other essential genetic, epigenetic, and non-genetic information to offspring. Transgenerational response to nutrition, early-life circumstances, and longevity Nico S. Rizzo (Loma Linda University and Karolinska Institute) discussed recent developments in research of epigenetics and transgenerational responses to nutrition and early-life circumstances, which may identify novel pathways providing insight into the pathogenesis of chronic diseases.16,17 While the sequencing and detailed mapping of the genome is essential for a basic understanding of DNA, knowing the mechanisms required for expressing the complex genetic information is essential for understanding the manifestation or repression of disease patterns. Epigenetics–a relatively young field–describes the mitotically heritable state of gene expression potential, enabled by the mechanisms of DNA methylation, histone modification and chromatin marks.18 Epigenetics involves the investigation of both the mechanisms of heritable and non-heritable changes in gene expression that do not involve modifications of the DNA coding sequence.19 The study of inherited and environmentallyacquired epigenetic alterations is important to understand disease etiology and effects of health-altering environmental events across multiple generations.20 Transgenerational epigenetic research, continued Rizzo, focuses on measurable outcomes in the offspring generation that are related to pre-conception exposures in the parental–or further removed– ancestral generations.17 An inclusive investigation of possible transgenerational epigenetic pathways should take into account social patterning and cultural inheritance in order to disentangle secondary pathways that influence measurable health outcomes in offspring. The socio-cultural context, environment, acquired and transferred health behaviors, and lifestyles of ancestral and offspring generations need to be considered. Figure 2 provides a schematic overview of interactions and pathways that influence adult health and longevity in the offspring generation. Interesting paternal transgenerational effects in humans have been observed in the erkalix cohort in northern Sweden.21,22 Meticulously maintained parish registries in this mainly agricultural region over more than a century recorded fluctuations in crop yields between years of abject famine and excess resulting in differences in longevity and specific causes of death in subsequent generations expressed through the paternal line.17,21 Although these observations were in concordance with expected differences between X versus Y chromoso.
