Giant tortoises are among the longest-lived vertebrate animals and, as such, provide an excellent model to study traits like longevity and age-related diseases. However, genomic and molecular evolutionary information on giant tortoises is scarce. Here, we describe a global analysis of the genomes of Lonesome George—the iconic last member of Chelonoidis abingdonii—and the Aldabra giant tortoise (Aldabrachelys gigantea). Comparison of these genomes with those of related species, using both unsupervised and supervised analyses, led us to detect lineage-specific variants affecting DNA repair genes, inflammatory mediators and genes related to cancer development. Our study also hints at specific evolutionary strategies linked to increased lifespan, and expands our understanding of the genomic determinants of ageing. These new genome sequences also provide important resources to help the efforts for restoration of giant tortoise populations.

Model organisms have provided fundamental evidence that aging can be delayed and longevity extended. These findings gave rise to a new era in aging research aimed at elucidating the pathways and networks controlling this complex biological process. The identification of 9 hallmarks of aging has established a framework to evaluate the relative contribution of each hallmark and the interconnections among them. In this review, we revisit these hallmarks with the information obtained exclusively through the generation of genetically modified mouse models that have a significant impact on the aging process. We discuss within each hallmark those interventions that accelerate aging or that have been successful at increasing lifespan, with the final goal of identifying the most promising antiaging avenues based on the current knowledge provided by in vivo models.

Alterations in iron status have frequently been associated with obesity and other metabolic disorders. The hormone hepcidin stands out as a key regulator in the maintenance of iron homeostasis by controlling the main iron exporter, ferroportin. Here we demonstrate that the deficiency in the hepcidin repressor matriptase-2 (Tmprss6) protects from high-fat diet-induced obesity. Tmprss6 ^−/− mice show a significant decrease in body fat, improved glucose tolerance and insulin sensitivity, and are protected against hepatic steatosis. Moreover, these mice exhibit a significant increase in fat lipolysis, consistent with their dramatic reduction in adiposity. Rescue experiments that block hepcidin up-regulation and restore iron levels in Tmprss6^−/− mice via anti-hemojuvelin (HJV) therapy, revert the obesity-resistant phenotype of Tmprss6^−/− mice. Overall, this study describes a role for matritpase-2 and hepcidin in obesity and highlights the relevance of iron regulation in the control of adipose tissue function.

GDF11 administration does not extend lifespan in a mouse model of premature aging

This study describes the development of a novel liposomal formulation incorporating 3-O-ethyl-L-ascorbic acid (EAA), a derivative of vitamin C. The EAA-loaded liposomes were fully characterized, particle size and zeta potential values suitable for drug delivery. The skin penetration studies revealed that liposomal formulation enhanced EAA retention in the skin compared to free EAA. Additionally, the impact of topical treatments with liposomal EAA on photo-aging markers in skin explants was investigated. EAA charged liposomes display a protective or stimulatory effect on cellular metabolism. Finally, liposomal EAA have a significant effect on the inflamatory markers, reducing the extracellular matrix degradation associated with UV-induced damage of skin. These findings provide valuable insights into the potential of liposomal formulations for the development of advanced cosmetic products.