Journals of Gerontology - Series A Biological Sciences and Medical Sciences, cilt.81, sa.3, 2026 (SCI-Expanded, SSCI, Scopus)
Background: 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 0.5mL of young plasma intravenously daily for 30 days, while 8-week-old rats received 0.25mL 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 ∼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 ∼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.