Rosuvastatin restores liver tissue-resident NK cell activation in aged mice by improving mitochondrial function
Year: 2025
Type: article
Abstract: Aging has an impact on Natural Killer (NK) cells surveillance against tumors and infections. Our study aims to assess the aging effects on metabolic and mitochondrial markers influencing NK cell activity. C57BL/6 J mice aged 12, 24, 48, and 72 weeks were used. Liver injury serum and histological markers, pro-inflammatory cytokines [IL-1β, IL-2, IL-6] and chemoattractant markers [CCL2, CXCL8] were assessed. Moreover, cholesterol metabolic markers [HMG-CoA synthetase, HMG-CoA reductase, mevalonate kinase], mitochondrial biogenesis [PGC1α] and functional gene markers [TFAM, HSPA9, Seahorse, apoptosis] in liver trNK cells, were assessed by RT-PCR. Senescence [p16, p21], exhaustion [PD-1, TIGIT, LAG3], activation [CD107a, NKp46], and chemokine receptor [CCR2, CXCR1] markers were assessed in trNK cells using flow cytometry. Liver trNK cells of aged mice were treated with Rosuvastatin [10μM] for 12 h. Data showed a linear increase in liver injury markers, pro-inflammatory and chemotaxis along aging. These results were associated with reductions in liver trNK cell counts and activations with a noticeable decrease in their chemoattractant receptor expressions. TrNK cells of aged mice exhibited elevated markers of senescence and exhaustion with a gradual increase in cholesterol accumulation. Mitochondrial biogenesis and functional gene markers showed a decrease in their expressions in aged mice while ameliorated following rosuvastatin treatment. Results were correlated with a decrease in cholesterol metabolism and restoring their NK cell activity. Our study demonstrates age-related cholesterol accumulation in trNK cells correlated with senescence and functional impairment. Rosuvastatin is suggested to boost, rejuvenate and recover NK cell functionality. • Aged mice exhibited elevation in liver injury markers of inflammation and fibrosis. • trNK cell showed decreased in counts and activity with increase in senescence and exhaustion markers along aging. • Accumulation of cholesterol in trNK cells impairs their functional capacity, contributing to liver dysfunction. • Rosuvastatin treatment improved trNK cell mitochondrial activity, indicates its potential to reduce age-related liver damage.
Source: Biomedicine & Pharmacotherapy
Authors: Johnny Amer, Ahmad Salhab, Rifaat Safadi
Institution: Hadassah Medical Center
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,610
OpenAlex ID: W4408778156