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In reality, this endeavour offers an invaluable opportunity to address critical biomedical challenges here at home. The extreme conditions of space, including microgravity, cosmic radiation and prolonged isolation, create a natural laboratory for studying human biology under stress, allowing us to explore the boundaries of human resilience. These exposures yield key insights into the biology of aging, the accelerated decline of physiological function and the early onset of chronic diseases. Among the organs most susceptible to environmental stress is the kidney, which is at high risk of failure during long\u2010duration spaceflight. Its sensitivity makes it an ideal model for understanding how stress accelerates degeneration, both in space and on Earth. By studying kidney function alongside broader cellular processes, we can illuminate how stress drives aging and chronic disease. This is particularly exemplified by the process of cellular necrosis (unprogrammed cell death), which represents a key central node as recently demonstrated. Necrosis acts upstream of processes like cellular senescence and tissue degeneration, and is the mechanism through which multiple environmental factors erode resilience and drive the progression of chronic diseases like kidney disease. Following this exploration of how stress accelerates biological decline, we examine strategies that may protect against such damage, preventing disease and preserving physiological resilience. Pharmaceuticals, with their ability to modulate physiology transiently, are especially powerful in dynamic, real\u2010world environments where stressors continually change. This \u2018chameleon effect\u2019 of pharmaceuticals offers the potential to uncouple biological trade\u2010offs and enhance adaptive capacity to stress. Understanding these processes in the space environment provides an unprecedented opportunity, difficult to reproduce\u00a0on Earth, to identify links between exposure and develop targeted interventions to enhance health and resilience on Earth.<\/jats:p>","DOI":"10.1113\/ep092652","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:00:18Z","timestamp":1787119218000},"page":"4064-4072","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tackling aging and chronic disease: How space exploration and the \u2018chameleon effect\u2019 of pharmaceuticals can lead the way"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-4529","authenticated-orcid":false,"given":"Carina","family":"Kern","sequence":"first","affiliation":[{"name":"LinkGevity, Babraham Research Campus  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Woods","sequence":"additional","affiliation":[{"name":"International Institute of Longevity (IIOL)  Warsaw Poland"},{"name":"Collider Health  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-5095","authenticated-orcid":false,"given":"Keith","family":"Siew","sequence":"additional","affiliation":[{"name":"London Tubular Centre Royal Free Hospital  London UK"},{"name":"Centre for Kidney and Bladder Health University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03483-9"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2020.05.048"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00050.2001"},{"issue":"3","key":"e_1_2_14_5_1","first-page":"199","article-title":"Roles of phospholipases A2 in brain cell and tissue injury associated with ischemia and excitotoxicity","volume":"16","author":"Bonventre J. 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