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The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. High-throughput mass-spectrometry-based approaches have recently contributed to identifying signalling response networks and gaining a more comprehensive understanding of the physiological adaptations occurring upon unrepaired DNA damage. The insulin-like signalling pathway has been implicated in a DNA damage response (DDR) network that includes epidermal growth factor (EGF)-, AMP-activated protein kinases (AMPK)- and the target of rapamycin (TOR)-like signalling pathways, which are known regulators of growth, metabolism, and stress responses. The same pathways, together with the autophagy-mediated proteostatic response and the decline in energy metabolism have also been found to be similarly regulated during natural aging, suggesting striking parallels in the physiological adaptation upon persistent DNA damage due to DNA repair defects and long-term low-level DNA damage accumulation occurring during natural aging. These insights will be an important starting point to study the interplay between signalling networks involved in progeroid syndromes that are caused by DNA repair deficiencies and to gain new understanding of the consequences of DNA damage in the aging process.<\/jats:p>","DOI":"10.3390\/ijms18112329","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T11:39:38Z","timestamp":1509968378000},"page":"2329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Omics Approaches for Identifying Physiological Adaptations to Genome Instability in Aging"],"prefix":"10.3390","volume":"18","author":[{"given":"Diletta","family":"Edifizi","sequence":"first","affiliation":[{"name":"Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany"},{"name":"Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD) and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany"},{"name":"Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD) and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.biochi.2003.11.003","article-title":"The base excision repair: Mechanisms and its relevance for cancer susceptibility","volume":"85","author":"Fortini","year":"2003","journal-title":"Biochimie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/cr.2007.115","article-title":"Mechanisms and functions of DNA mismatch repair","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev.biochem.052308.093131","article-title":"The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway","volume":"79","author":"Lieber","year":"2010","journal-title":"Annu. 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