Damaged DNA marching out of aging nucleus

of infection is a key feature of aging, and includes senescent cells that secrete cytokines. Yet, what are the intrinsic processes that initiate ‘inflammaging’, and possibly other forms of sterile inflammation, like autoimmunity? Self-DNA has long been suspected as trigger and target of autoimmunity, as anti-nuclear antibodies, antidsDNA (double-stranded DNA) antibodies and plasma DNA are observed in autoimmune patients of lupus and rheumatoid arthritis. In studying the initiating events leading to autoimmune arthritis in mice deficient for the lysosomal nuclease DNASE2A, we revealed an unexpected ‘hidden’ source of this inflammatory DNA— the cell’s own nucleus [1]. We discovered a cell autonomous nuclear-to-lysosome pathway that removes immunogenic self-DNA. In healthy cells, damaged and irreparable nuclear DNA fragments are trafficked to the Editorial