caa a22 4500 606176071 CHVBK 20210128100745.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00018-015-1896-0 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1896-0 The mechanism of ageing: primary role of transposable elements in genome disintegration [Elektronische Daten] [Ádám Sturm, Zoltán Ivics, Tibor Vellai] Understanding the molecular basis of ageing remains a fundamental problem in biology. In multicellular organisms, while the soma undergoes a progressive deterioration over the lifespan, the germ line is essentially immortal as it interconnects the subsequent generations. Genomic instability in somatic cells increases with age, and accumulating evidence indicates that the disintegration of somatic genomes is accompanied by the mobilisation of transposable elements (TEs) that, when mobilised, can be mutagenic by disrupting coding or regulatory sequences. In contrast, TEs are effectively silenced in the germ line by the Piwi-piRNA system. Here, we propose that TE repression transmits the persistent proliferation capacity and the non-ageing phenotype (e.g., preservation of genomic integrity) of the germ line. The Piwi-piRNA pathway also operates in tumorous cells and in somatic cells of certain organisms, including hydras, which likewise exhibit immortality. However, in somatic cells lacking the Piwi-piRNA pathway, gradual chromatin decondensation increasingly allows the mobilisation of TEs as the organism ages. This can explain why the mortality rate rises exponentially throughout the adult life in most animal species, including humans. Springer Basel, 2015 Lifespan determination nationallicence Age-related diseases nationallicence Retroelements nationallicence Repetitive sequences nationallicence Chromatin relaxation nationallicence Non-coding small RNAs nationallicence Methylation nationallicence Cancer nationallicence Sturm Ádám Department of Genetics, Eötvös Loránd University, Pázmány Péter stny. 1/C, Budapest, Hungary aut Ivics Zoltán Division of Medical Biotechnology, Paul Ehrlich Institute, 63225, Langen, Germany aut Vellai Tibor Department of Genetics, Eötvös Loránd University, Pázmány Péter stny. 1/C, Budapest, Hungary aut Cellular and Molecular Life Sciences Springer Basel 72/10(2015-05-01), 1839-1847 1420-682X 72:10<1839 2015 72 18 https://doi.org/10.1007/s00018-015-1896-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 editorial jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1896-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sturm Ádám Department of Genetics, Eötvös Loránd University, Pázmány Péter stny. 1/C, Budapest, Hungary aut NATIONALLICENCE 700 1- Ivics Zoltán Division of Medical Biotechnology, Paul Ehrlich Institute, 63225, Langen, Germany aut NATIONALLICENCE 700 1- Vellai Tibor Department of Genetics, Eötvös Loránd University, Pázmány Péter stny. 1/C, Budapest, Hungary aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/10(2015-05-01), 1839-1847 1420-682X 72:10<1839 2015 72 18