Immunity & ageing : I & A · 2025
Obese plasma transfer accelerates cellular aging in the C57BL/6 mouse model.
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Shahabi Nejad Shabnam, Zand Hamid, Rastgoo Samira, Bahreini Boroujeni Leyli Zahra, Abedini Najafabadi Mehdi, Asadi Saman, Hamishe Bahar Reyhane, Shimi Ghazaleh
Аннотация
BACKGROUND: Obesity induces chronic inflammation and cellular senescence, contributing to metabolic and immune dysfunction. This study investigates the effects of plasma obtained from obese and non-obese C57BL/6 donor mice on senescence and inflammation markers in recipient mice.
METHODS: Recipient C57BL/6 mice received intraperitoneal injections of 150 μl of pooled plasma from either obese (PO group) or non-obese (PNO group) donors once weekly for four weeks. Body weight, epididymal adiposity index, and thymus index were recorded. Senescence-associated β-galactosidase (SA-β-gal) activity was assessed in epididymal white adipose tissue (eWAT) and peripheral blood mononuclear cells (PBMCs). Gene expression of p16, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Plasma concentrations of IL-6 and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS: Mice in the PO group showed significantly increased SA-β-gal activity in eWAT (P < 0.05) and PBMCs (P < 0.001) compared to the PNO group. In eWAT, p16 expression was significantly elevated (P = 0.019; log₁₀-fold change: 1.48). In PBMCs, IL-6 (P < 0.001; log₁₀-fold change: 0.90), p16 (P < 0.001; log₁₀-fold change: 1.41), and TNF-α (P < 0.001; log₁₀-fold change: 2.83) expressions were significantly upregulated in the PO group. No significant differences were observed in plasma cytokines, body weight, epididymal adiposity, or thymus index.
CONCLUSIONS: These results indicate that the pro-inflammatory and pro-senescence effects of obese plasma are not limited to the original donor but can actively transfer aging-related changes and immune dysfunctions to healthy recipient tissues, highlighting the need for further therapeutic exploration.
METHODS: Recipient C57BL/6 mice received intraperitoneal injections of 150 μl of pooled plasma from either obese (PO group) or non-obese (PNO group) donors once weekly for four weeks. Body weight, epididymal adiposity index, and thymus index were recorded. Senescence-associated β-galactosidase (SA-β-gal) activity was assessed in epididymal white adipose tissue (eWAT) and peripheral blood mononuclear cells (PBMCs). Gene expression of p16, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Plasma concentrations of IL-6 and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS: Mice in the PO group showed significantly increased SA-β-gal activity in eWAT (P < 0.05) and PBMCs (P < 0.001) compared to the PNO group. In eWAT, p16 expression was significantly elevated (P = 0.019; log₁₀-fold change: 1.48). In PBMCs, IL-6 (P < 0.001; log₁₀-fold change: 0.90), p16 (P < 0.001; log₁₀-fold change: 1.41), and TNF-α (P < 0.001; log₁₀-fold change: 2.83) expressions were significantly upregulated in the PO group. No significant differences were observed in plasma cytokines, body weight, epididymal adiposity, or thymus index.
CONCLUSIONS: These results indicate that the pro-inflammatory and pro-senescence effects of obese plasma are not limited to the original donor but can actively transfer aging-related changes and immune dysfunctions to healthy recipient tissues, highlighting the need for further therapeutic exploration.