We also thank S. Jeay (Novartis Pharma AG, Basel Area, Switzerland; NVP-AEW541), M. Holzenberger (Faculte de medecine Pierre et Marie Curie, Paris; Igf1r-haploinsuficient mice), M.J. Munoz Ruiz (Universidad Pablo de Olavide, Sevilla; GM6 C. elegans strain) and F.G. Wulczyn (Universitatsmedizin Berlin, Berlin; miR-125a sponge) for providing reagents. We thank A. Moyano and R. Feijoo for excellent technical assistance, and the Servicio de Histopatologia (IUOPA) for histological studies. This work was supported by grants from Ministerio de Economia y Competitividad (C.L.-O.), Instituto de Salud Carlos III (RTICC) (C.L.-O.), and Principado de Asturias, Spain (J.M.P.F). We also thank the generous support by J. I. Cabrera, A. I. Campos and M. Secades. The Instituto Universitario de Oncologia is supported by Fundacion Bancaria Caja de Ahorros de Asturias. C.L.-O. is an Investigator of the Botin Foundation supported by Banco Santander through its Santander Universities Global Division. Work in the Green laboratory is supported by Bloodwise (grant ref. 13003), the Wellcome Trust (grant ref. 104710/Z/14/Z), the Medical Research Council, the Kay Kendall Leukaemia Fund, the Cambridge National Institute for Health Research Biomedical Research Center, the Cambridge Experimental Cancer Medicine Centre, the Leukemia and Lymphoma Society of America (grant ref. 07037), and a core support grant from the Wellcome Trust and the Medical Research Council to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute.