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.

Intestinal or cloacal strictures that resulted in intestinal obstruction were diagnosed in six green sea turtles (Chelonia mydas) from three rehabilitation facilities and two zoologic parks. The etiologies of the strictures were unknown in these cases. It is likely that anatomic adaptations of the gastrointestinal tract unique to the green sea turtle's herbivorous diet, paired with causes of reduced intestinal motility, may predispose the species to intestinal damage and subsequent obstructive intestinal disease. In aquarium-maintained green sea turtles, obesity, diet, reduced physical activity, chronic intestinal disease, and inappropriate or inadequate antibiotics might also be potential contributing factors. Clinical, radiographic, and hematologic abnormalities common among most of these sea turtles include the following: positive buoyancy; lethargy; inappetence; regurgitation; obstipation; dilated bowel and accumulation of oral contrast material; anemia; hypoglycemia; hypoalbuminemia; hypocalcemia; and elevated creatine kinase, aspartate aminotransferase, and blood urea nitrogen. Although these abnormalities are nonspecific with many possible contributing factors, intestinal disease, including strictures, should be considered a differential in green sea turtles that demonstrate all or a combination of these clinical findings. Although diagnostic imaging, including radiographs, computed tomography, or magnetic resonance imaging, are important in determining a cause for suspected gastrointestinal disease and identifying an anatomic location of obstruction, intestinal strictures were not successfully identified when using these imaging modalities. Lower gastrointestinal contrast radiography, paired with the use of oral contrast, was useful in identifying the suspected site of intestinal obstruction in two cases. Colonoscopy was instrumental in visually diagnosing intestinal stricture in one case. Therefore, lower gastrointestinal contrast radiography and colonoscopy should be considered in green turtles when gastrointestinal obstructions are suspected. Although partial strictures of the cloacal opening may be identified on gross examination and might be managed with appropriate medical treatment, surgical intervention or humane euthanasia are likely the only options for sea turtles once small or large intestinal strictures have formed.

The primary purpose of this study was to establish plasma biochemistry parameters for healthy recently wild-caught purple mouth moray eels (Gymnothorax vicinus) to provide a baseline of data for improved medical care in an aquarium or zoologic setting and for wild health assessments. Thirty-one clinically healthy purple mouth moray eels of unknown age and sex were caught from the wild, and were anesthetized 50 days following capture for blood collection from the ventral coccygeal vein. The median plasma biochemistry values were as follows: hematocrit = 21%, creatinine kinase = 2,100 U/L, lactate dehydrogenase = 97 U/L, aspartate aminotransferase = 88 U/L, alanine aminotransferase = 51 U/L, alkaline phosphatase 3,939 U/L, gamma-glutamyl transpeptidase = 1 U/L, amylase = 40 U/L, blood urea nitrogen = < 11 mg/dl, glucose = 21 mg/dl, calcium = 12.5 mg/dl, triglyceride = 206 mg/dl, creatinine = 0.1 mg/dl, cholesterol = 334 mg/dl, total bilirubin = < 0.1 mg/dl, phosphorus = 6.5 mg/dl, total protein = 4.2 g/dl, albumin = 1.5 g/dl, globulin = 2.7 g/dl, albumin/ globulin ratio = 0.6, sodium = 185 mmol/L, potassium = 3.7 mmol/L, and chloride = 175 mmol/L. Alkaline phosphatase isoenzyme results indicate that the majority of the plasma alkaline phosphatase is the liver isoenzyme. The data acquired in this study also provide baseline values for cholesterol and triglycerides in recently wild-caught moray eels to aid in monitoring elevations to these values in an aquarium setting over time so adjustments to the dietary regime may be utilized to prevent or improve conditions such as lipid keratopathy.

Using DNA methylation profiles ( n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.