Uncompromised ten-year survival of oldest old carrying somatic mutations in DNMT3A and TET2

Abstract

Recent large-scale sequencing studies report recurrent somatic mutations in the blood of elderly individuals in genes previously linked to clonal expansion of hematopoietic stem cells [1-4]. Particularly for DNMT3A and TET2, a steep ageassociated increase in the prevalence of somatic mutations is observed from middle age onward [2-4]. In addition, prospective analyses performed in predominantly middle-aged individuals show an increased risk for all-cause mortality for carriers of such mutations as compared with non-carriers [3,4]. Jointly, these data suggest a rapidly increasing vulnerability among the elderly for adverse health effects associated with clonal expansion of hematopoietic stem cells.