{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:05:53Z","timestamp":1788984353500,"version":"build-2803163510"},"reference-count":142,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"medical faculty at Heinrich-Heine University, Duesseldorf"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Every individual at some point encounters the progressive biological process of aging, which is considered one of the major risk factors for common diseases. The main drivers of aging are oxidative stress, senescence, and reactive oxygen species (ROS). The renin\u2013angiotensin\u2013aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure, which is caused by an imbalance of electrolytes. During activation of the RAAS, binding of angiotensin II (ANG II) to angiotensin II type 1 receptor (AGTR1) activates intracellular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate superoxide anions and promote uncoupling of endothelial nitric oxide (NO) synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show downregulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase sirtuin-1 (SIRT1) has a significant impact on the aging process, with reduced activity with age. However, GS\/BS patients generally sustain higher levels of sirtuin-1 (SIRT1) activity than age-matched healthy individuals. SIRT1 expression in GS\/BS patients tends to be higher than in healthy age-matched individuals; therefore, it can be assumed that there will be a trend towards healthy aging in these patients. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS\/BS patients and how this might impact healthy aging. We further propose future research directions for studying the etiology of GS\/BS at the molecular level using patient-derived renal stem cells and induced pluripotent stem cells.<\/jats:p>","DOI":"10.3390\/ijms25179332","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T11:54:10Z","timestamp":1724846050000},"page":"9332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Untangling the Uncertain Role of Overactivation of the Renin\u2013Angiotensin\u2013Aldosterone System with the Aging Process Based on Sodium Wasting Human Models"],"prefix":"10.3390","volume":"25","author":[{"given":"Chantelle","family":"Thimm","sequence":"first","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6075-6761","authenticated-orcid":false,"given":"James","family":"Adjaye","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Zayed Centre for Research into Rare Diseases in Children (ZCR), EGA Institute for Women\u2019s Health, University College London (UCL), 20 Guilford Street, London WC1N 1DZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","unstructured":"Fountain, J.H., Kaur, J., and Lappin, S.L. 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