Search

The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways1,2. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer3,4,5,6, but its precise role in aging remains to be elucidated. Here, we find that two different mouse models of progeria are characterized by intestinal dysbiosis with alterations that include an increase in the abundance of Proteobacteria and Cyanobacteria, and a decrease in the abundance of Verrucomicrobia. Consistent with these findings, we found that human progeria patients also display intestinal dysbiosis and that long-lived humans (that is, centenarians) exhibit a substantial increase in Verrucomicrobia and a reduction in Proteobacteria. Fecal microbiota transplantation from wild-type mice enhanced healthspan and lifespan in both progeroid mouse models, and transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial effects of reestablishing a healthy microbiome. Our results demonstrate that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases. Sin financiación 36.130 JCR (2019) Q1, 2/297 Biochemistry & Molecular Biology, 3/195 Cell Biology, 1/138 Medicine, Research & Experimental 15.812 SJR (2019) Q1, 2/271 Biochemistry, Genetics and Molecular Biology (miscellaneous), 5/2754 Medicine (miscellaneous) No data IDR 2019 UEM

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., We thank Banco Santander for funding a short stay of S.F.-R. and D.C.-I. at Yale University. V.Q. is supported by grants from the Principado de Asturias and Ministerio de Economía y Competitividad, including FEDER funding. L.F.K.K. is supported by an FPI fellowship associated with BFU2014-55090-P (FEDER). T.M.-B. is supported by MINECO BFU2017-86471-P (MINECO/FEDER, UE), an NIH U01 MH106874 grant, the Howard Hughes International Early Career programme, Obra Social ‘La Caixa’ and Secretaria d’Universitats i Recerca, and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya. C.L.-O. is supported by grants from the European Research Council (DeAge; ERC Advanced Grant), Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (RTICC) and Progeria Research Foundation. The Instituto Universitario de Oncología is supported by Fundación Bancaria Caja de Ahorros de Asturias. We also thank staff at the Galapagos National Park and Galapagos Conservancy for logistic and financial support.