Relationship between red blood cell lifespan and endogenous carbon monoxide in the common bottlenose dolphin and beluga

Certain deep-diving marine mammals (i.e., northern elephant seal (Mirounga angustirosis), Weddell seal (Leptonychotes weddellii)) have blood carbon monoxide (CO) levels that are comparable to those of chronic cigarette smokers. Most CO produced in humans is a by-product of heme degradation, which is released when red blood cells (RBC) are destroyed. Elevated CO can occur in humans when RBC lifespan decreases. The contribution of RBC turnover to CO concentrations in marine mammals is unknown. Here, we report the first RBC lifespans in two healthy, marine mammal species with different diving capacities and heme stores, the shallow diving bottlenose dolphin (Tursiops truncatus) and deep-diving beluga (Delphinapterus leucas) and relate the lifespans to the levels of CO in blood and breath. The belugas, with high blood heme stores, had the longest mean RBC lifespan compared to humans and bottlenose dolphins. Both cetacean species were found to have three times higher blood CO content compared to humans. The estimated CO production rate from heme degradation indicates some marine mammals may have additional mechanisms for CO production, or delay CO removal from the body, potentially from long duration breath-holds

Universal DNA methylation age across mammalian tissues

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals

Structural determinants of the SINE B2 element embedded in the long non-coding RNA activator of translation AS Uchl1

Pervasive transcription of mammalian genomes leads to a previously underestimated level of complexity in gene regulatory networks. Recently, we have identified a new functional class of natural and synthetic antisense long non-coding RNAs (lncRNA) that increases translation of partially overlapping sense mRNAs. These molecules were named SINEUPs, as they require an embedded inverted SINE B2 element for their UP-regulation of translation. Mouse AS Uchl1 is the representative member of natural SINEUPs. It was originally discovered for its role in increasing translation of Uchl1 mRNA, a gene associated with neurodegenerative diseases. Here we present the secondary structure of the SINE B2 Transposable Element (TE) embedded in AS Uchl1. We find that specific structural regions, containing a short hairpin, are required for the ability of AS Uchl1 RNA to increase translation of its target mRNA. We also provide a high-resolution structure of the relevant hairpin, based on NMR observables. Our results highlight the importance of structural determinants in embedded TEs for their activity as functional domains in lncRNAs

Universal DNA methylation age across mammalian tissues

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.Publisher PDFPeer reviewe

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals

The Value of Ex Situ Cetacean Populations in Understanding Reproductive Physiology and Developing Assisted Reproductive Technology for Ex Situ and In Situ Species Management and Conservation Efforts

Wild cetacean populations have uncertain futures in the face of shifting climate conditions and the continued encroachment of their unique ecosystem by human activities. Core conservation efforts focus on habitat protection and understanding the natural ecology of a species, but such efforts arein complete without a comprehensive understanding of a species’ physiology. Ex situ populations of cetaceans provide a unique opportunity to collect this physiological data, and thereby serve as an important component of any conservation effort. The sustainability of captive cetacean populations is in turn dependent on a thorough understanding of reproductive physiology, and such research has facilitated the development of assisted reproductive technology (ART). ART, specifically gamete preservation for genome resource banking, artificial insemination and sperm sexing, has been used to significantly enhance the genetic, reproductive and social management of ex situ cetaceans. For endangered cetaceans and other marine mammals, ART will permit the establishment of permanent repositories of valuable genetic material which could be used to maximize their reproductive potential and maintain the species’ genetic diversity; an approach that, when combined with in situ conservation efforts, may prevent their extinction

The Value of Ex Situ Cetacean Populations in Understanding Reproductive Physiology and Developing Assisted Reproductive Technology for Ex Situ and In Situ Species Management and Conservation Efforts

Wild cetacean populations have uncertain futures in the face of shifting climate conditions and the continued encroachment of their unique ecosystem by human activities. Core conservation efforts focus on habitat protection and understanding the natural ecology of a species, but such efforts arein complete without a comprehensive understanding of a species’ physiology. Ex situ populations of cetaceans provide a unique opportunity to collect this physiological data, and thereby serve as an important component of any conservation effort. The sustainability of captive cetacean populations is in turn dependent on a thorough understanding of reproductive physiology, and such research has facilitated the development of assisted reproductive technology (ART). ART, specifically gamete preservation for genome resource banking, artificial insemination and sperm sexing, has been used to significantly enhance the genetic, reproductive and social management of ex situ cetaceans. For endangered cetaceans and other marine mammals, ART will permit the establishment of permanent repositories of valuable genetic material which could be used to maximize their reproductive potential and maintain the species’ genetic diversity; an approach that, when combined with in situ conservation efforts, may prevent their extinction