Dataset Information

Using zebrafish models to explore genetic and epigenetic impacts on evolutionary developmental origins of aging.

ABSTRACT: Can we reset, reprogram, rejuvenate, or reverse the organismal aging process? Certain genetic manipulations could at least reset and reprogram epigenetic dynamics beyond phenotypic plasticity and elasticity in cells, which can be manipulated further into organisms. However, in a whole complex aging organism, how can we rejuvenate intrinsic resources and infrastructures in an intact and noninvasive manner? The incidence of diseases increases exponentially with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but essentially inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these 2 phenomena to rejuvenate over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states based on diverse epigenotypes in response to intrinsic or extrinsic environmental cues and genetic perturbations. We hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds and windows of plasticity and its robustness by molecular genetic and chemical epigenetic approaches, we have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during their embryonic and/or larval stages ("embryonic/larval senescence"). Subsequently, at least some of these mutant animals were found to show a shortened life span, whereas others would be expected to live longer into adulthood. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and its regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes, genotypes, and epigenotypes that can be linked to the senescence phenotype, which facilitates searching for the evolutionary and developmental origins of aging in vertebrates.

SUBMITTER: Kishi S

PROVIDER: S-EPMC3969878 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Using zebrafish models to explore genetic and epigenetic impacts on evolutionary developmental origins of aging.

Kishi Shuji S

Translational research : the journal of laboratory and clinical medicine 20131025 2

Can we reset, reprogram, rejuvenate, or reverse the organismal aging process? Certain genetic manipulations could at least reset and reprogram epigenetic dynamics beyond phenotypic plasticity and elasticity in cells, which can be manipulated further into organisms. However, in a whole complex aging organism, how can we rejuvenate intrinsic resources and infrastructures in an intact and noninvasive manner? The incidence of diseases increases exponentially with age, accompanied by progressive dete ...[more]

PMID: 24239812

Similar Datasets

Project description:The incidence of diseases increases rapidly with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but mostly inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states in response to different environmental or genetic perturbations. On the one hand, we hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds of adaptive plasticity by chemical genetic approaches, we have been investigating whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during embryogenesis ("embryonic senescence"), subsequently showing shortened lifespan in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes and small molecular compounds that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins of aging in vertebrates. This article is part of a Special Issue entitled: Animal Models of Disease.

Project description:The COVID-19 pandemic has caused a global societal, economic, and social upheaval unseen in living memory. There have been substantial cross-national differences in the kinds of policies implemented by political decision-makers to prevent the spread of the virus, to test the population, and to manage infected patients. Among other factors, these policies vary with politicians' sex: early findings indicate that, on average, female leaders seem more focused on minimizing direct human suffering caused by the SARS-CoV-2 virus, while male leaders implement riskier short-term decisions, possibly aiming to minimize economic disruptions. These sex differences are consistent with broader findings in psychology, reflecting women's stronger empathy, higher pathogen disgust, health concern, care-taking orientation, and dislike for the suffering of other people-as well as men's higher risk-taking, Machiavellianism, psychopathy, narcissism, and focus on financial indicators of success and status. This review article contextualizes sex differences in pandemic leadership in an evolutionary framework. Evolution by natural selection is the only known process in nature that organizes organisms into higher degrees of functional order, or counteracts the unavoidable disorder that would otherwise ensue, and is therefore essential for explaining the origins of human sex differences. Differential sexual selection and parental investment between males and females, together with the sexual differentiation of the mammalian brain, drive sex differences in cognition and behavioral dispositions, underlying men's and women's leadership styles and decision-making during a global pandemic. According to the sexually dimorphic leadership specialization hypothesis, general psychobehavioral sex differences have been exapted during human evolution to create sexually dimorphic leadership styles. They may be facultatively co-opted by societies and/or followers when facing different kinds of ecological and/or sociopolitical threats, such as disease outbreaks or intergroup aggression. Early evidence indicates that against the invisible viral foe that can bring nations to their knees, the strategic circumspection of empathic feminine health "worriers" may bring more effective and humanitarian outcomes than the devil-may-care incaution of masculine risk-taking "warriors".

Project description:Epigenetic marks, including DNA methylation, are modifiable molecular factors that may underlie mental disorders, especially responses to trauma, including the development of and resilience to posttraumatic stress disorder (PTSD). Previous work has identified differential DNA methylation at CpG dinucleotide sites genomewide between trauma exposed individuals with and without PTSD, suggesting a role for epigenetic potential-the capacity to epigenetically regulate behavior and physiology in response to lived experiences. The human species is characterized by an increased period of adaptive plasticity during brain development. The evolutionary history of epigenetic potential in relation to adaptive plasticity is currently unknown. Using phylogenetic methods and functional annotation analyses, we trace the evolution of over 7000 CpG dinucleotides, including 203 associated with PTSD, during the descent of humans in during mammalian evolution and characterize the biological significance of this evolution. We demonstrate that few (7%) PTSD-associated CpG sites are unique to humans, while the vast majority of sites have deep evolutionary origins: 73 and 93% were unambiguously present in the last common ancestor of humans/orangutans and humans/chimpanzees, respectively. Genes proximal to evolved PTSD-associated CpG sites revealed significant enrichment for immune function during recent human evolution and regulation of gene expression during more ancient periods of human evolution. Additionally, 765 putative transcription factor binding motifs (TFBMs) were identified that overlap with PTSD-associated CpG sites. Elucidation of the evolutionary history of PTSD-associated CpG sites may provide insights into the function and origin of epigenetic potential in trauma responses, generally, and PTSD, specifically. The human capacity to respond to trauma with stable physiologic and behavioral changes may be due to epigenetic potentials that are shared among many mammalian species.

Dataset Information

Using zebrafish models to explore genetic and epigenetic impacts on evolutionary developmental origins of aging.

Publications

Using zebrafish models to explore genetic and epigenetic impacts on evolutionary developmental origins of aging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets