Long telomeres are associated with clonality in wild populations of the fissiparous starfish Coscinasterias tenuispina

7 páginas, 4 figuras, 3 tablasTelomeres usually shorten during an organism’s lifespan and have thus been used as an aging and health marker. When telomeres become sufficiently short, senescence is induced. The most common method of restoring telomere length is via telomerase reverse transcriptase activity, highly expressed during embryogenesis. However, although asexual reproduction from adult tissues has an important role in the life cycles of certain species, its effect on the aging and fitness of wild populations, as well as its implications for the long-term survival of populations with limited genetic variation, is largely unknown. Here we compare relative telomere length of 58 individuals from four populations of the asexually reproducing starfish Coscinasterias tenuispina. Additionally, 12 individuals were used to compare telomere lengths in regenerating and non-regenerating arms, in two different tissues (tube feet and pyloric cecum). The level of clonality was assessed by genotyping the populations based on 12 specific microsatellite loci and relative telomere length was measured via quantitative PCR. The results revealed significantly longer telomeres in Mediterranean populations than Atlantic ones as demonstrated by the Kruskal–Wallis test (K=24.17, significant value: P-valueo0.001), with the former also characterized by higher levels of clonality derived from asexual reproduction. Telomeres were furthermore significantly longer in regenerating arms than in non-regenerating arms within individuals (pyloric cecum tissue: Mann–Whitney test, V=299, P-valueo10− 6; and tube feet tissue Student's t= 2.28, P-value =0.029). Our study suggests that one of the mechanisms responsible for the long-term somatic maintenance and persistence of clonal populations is telomere elongation.This research was financially supported by a PhD fellowship FPI-MICINN (BES-2011-044154) (ACG), the European ASSEMBLY project (227799), the Swedish Royal Academy of Sciences (ACG) and the Spanish Government project CTM2010-22218-C02. The research was also supported by a ‘Juan de la Cierva’ contract from the Spanish Government (RPP) and by the Adlerbertska Research Foundation (HNS).Peer reviewe

gRASping the redox lever to modulate cancer cell fate signaling

RAS proteins are critical regulators of signaling networks controlling diverse cellular functions such as cell proliferation and survival and its mutation are among the most powerful oncogenic drivers in human cancers. Despite intense efforts, direct RAS-targeting strategies remain elusive due to its “undruggable” nature. To that end, bulk of the research efforts has been directed towards targeting upstream and/or downstream of RAS signaling. However, the therapeutic efficacies of these treatments are limited in the long run due to the acquired drug resistance in RAS-driven cancers. Interestingly, recent studies have uncovered a potential role of RAS in redox-regulation as well as the interplay between ROS and RAS-associated signaling networks during process of cancer initiation and progression. More specifically, these studies provide ample evidence to implicate RAS as a redox-rheostat, manipulating ROS levels to provide a redox-milieu conducive for carcinogenesis. Importantly, the understanding of RAS-ROS interplay could provide us with novel targetable vulnerabilities for designing therapeutic strategies. In this review, we provide a brief summary of the advances in the field to illustrate the dual role of RAS in redox-regulation and its implications in RAS signaling outcomes and also emerging redox-based strategies to target RAS-driven cancers