The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process

Home range size variation in a recovering wolf population: evaluating the effect of environmental, demographic, and social factors

Home range size in mammals is a key ecological trait and an important parameter in conservation planning, and has been shown to be influenced by ecological, demographic and social factors in animal populations. Information on space requirements is especially important for carnivore species which range over very large areas and often come into direct conflict with human interest. We used long-term telemetry-location data from a recovering wolf population in Scandinavia to investigate variation in home range size in relation to environmental and social characteristics of the different packs. Wolves showed considerable variation in home range size, which ranged from 259 to 1,676 km(2). Although wolf density increased fourfold during the study period, we found no evidence that intraspecific competition influenced range size. Local variation in moose density, which was the main prey for most packs, did not influence wolf home range size. Home ranges increased with latitude and elevation and decreased with increased roe deer density. Although prey biomass alone did not influence range size, our data suggest that there is a correlation between habitat characteristics, choice of prey species and possible hunting success, which currently combine to shape home range size in Scandinavian wolves

Strain difference of cadmium-induced testicular toxicity in inbred Wistar-Imamichi and Fischer 344 rats

Previously, we reported that Wistar-Imamichi (WI) rats are highly resistance to cadmium (Cd)-induced lethality and hepatotoxicity compared to Fischer 344 (F344) rats. Since the testes are one of the most sensitive organs to acute Cd toxicity, we examined possible strain-related differences in Cd-induced testicular toxicity between inbred WI and F344 rats. Rats were treated with a single dose of 0.5, 1.0 or 2.0 mg Cd/kg, as CdCl2, sc and killed at 24 h later. Cd at doses of 1.0 and 2.0 mg/kg induced severe testicular hemorrhage, as assessed by pathologically and testis hemoglobin content, in F344 rats, but not WI rats. After Cd treatment (2.0 mg/kg), testicular Cd content was significantly lower in WI rats than in the F344 rats, indicating a toxiokinetic mechanism for the observed strain difference. Thus, the remarkable resistance to Cd-induced testicular toxicity in WI rats is associated, at least in part, with lower testicular accumulation of Cd. When zinc (Zn; 10 mg/kg, sc) was administered in combination with Cd (2.0 mg/kg) to F344 rats, the Cd-induced increase in testicular hemoglobin content, indicative of hemorrhage, was significantly reduced. Similarly, testicular Cd content was significantly decreased with Zn co-treatment compared to Cd treatment alone. Thus, it can be concluded that testicular Cd accumulation partly competes with Zn transport systems and that these systems may play an important role in the strain-related differences in Cd-induced testicular toxicity between WI and F344 rats