Duvenci Birben, OzlemTeker, Hikmet TanerKeskin, SedaBaba, BurcuKocpinar, Enver FehimYildirim, VesilaCeylani, Taha2026-03-012026-03-0120261079-50061758-535X10.1093/gerona/glag007https://doi.org/10.1093/gerona/glag007https://hdl.handle.net/20.500.14720/29839Background Heterochronic plasma exchange is widely used to investigate systemic aging; however, its pulmonary consequences particularly regarding oxidative stress, antioxidant defense, and tissue architecture have not been systematically examined. Methods Twenty-four-month-old male Sprague-Dawley rats received 0.5 mL of young plasma intravenously daily for 30 days, while 8-week-old rats received 0.25 mL of aged plasma. After treatment, lung tissues were analyzed histologically, biochemically, and molecularly. Results Quantitative PCR showed that young plasma markedly upregulated antioxidant defenses, with SOD and CAT expression increasing by similar to 2.5-fold and 1.8-fold, respectively (p < 0.01), accompanied by higher SOD and GPX enzyme activities (p < 0.05). Additional antioxidant genes (GR, GST, TXN/TXNR) were also significantly upregulated, confirming a broad activation of the antioxidant network. In contrast, aged plasma suppressed antioxidant responses, reducing CAT activity by similar to 35% (p < 0.01) and similarly decreasing other enzymes. Histological analyses revealed preserved alveolar structure, thinner septa, and reduced inflammation in old + young plasma rats, while young + old plasma transfer caused structural deterioration. Immunohistochemistry confirmed increased GPX, SOD, and CAT expression in aged rats receiving young plasma, consistent with transcriptional and protein-level activation. Moreover, heterochronic plasma exchange attenuated collagen accumulation, suggesting reduced fibrillar matrix deposition, and restored the balance between alveolar epithelial Type I (AT1) and Type II (AT2) cells, indicating improved epithelial homeostasis. Toluidine Blue staining showed decreased mast-cell density after young plasma treatment (p < 0.05), reinforcing its anti-inflammatory effect. Conclusions Young plasma exerts regenerative and anti-inflammatory actions in the aged lung, highlighting it as a key target of systemic rejuvenation.eninfo:eu-repo/semantics/closedAccessPlasma ExchangeLung TissueAntioxidantOxidative StressSprague-DawleyArticle