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<p>Aging is accompanied by the accumulation of senescent cells and chronic low-grade inflammation, which together contribute to functional decline and tissue remodeling across organs. We previously reported that long-term nacre extract supplementation can delay age-related deterioration when initiated early; however, whether it can provide benefit under post-onset intervention conditions remains unclear. Here, we evaluated a water-soluble nacre extract derived from <i>Pinctada fucata</i> using (i) senescence-accelerated mouse prone 8 (SAMP8) mice and (ii) a D-galactose–induced aging paradigm, with treatment administered after the emergence of age-related phenotypes. In SAMP8 mice, nacre extract improved cognitive and neuromuscular performance, including Y-maze spontaneous alternation, novel object recognition, and forelimb grip strength, and showed a partial improvement in composite aging indices. These benefits were accompanied by reduced senescence-associated markers (p16, p21, and phosphorylated histone H2AX (γH2AX)) in skeletal muscle and peripheral organs, suppression of inflammation-associated signaling in skeletal muscle, and improved redox-related marker profiles. Nacre extract also increased satellite cell– and contractile marker–related immunoreactivity in aged skeletal muscle, suggesting improved regeneration- and maturation-related tissue characteristics. In the D-galactose model, nacre extract was introduced after impairments emerged and administered during the final 11&#xa0;weeks of continued D-galactose exposure; under these post-onset intervention conditions, nacre extract improved grip strength, showed trends toward improved cognitive performance, and reduced senescence-associated markers in skeletal muscle and adipose tissue, supporting reproducibility across paradigms. Collectively, these findings indicate that nacre extract attenuates aging-associated functional and tissue alterations under post-onset intervention conditions by attenuating senescence- and inflammation-associated tissue responses and improving organism-level homeostasis.</p>

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Nacre extract attenuates age-related functional and tissue alterations under post-onset intervention conditions in two murine aging models

  • 期刊论文

  • 发表日期：

    2026年6月15日

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  • Momoko Kawaminami,
  • Saki Kimoto,
  • Hana Yamamoto,
  • Yasushi Hasegawa

摘要

Aging is accompanied by the accumulation of senescent cells and chronic low-grade inflammation, which together contribute to functional decline and tissue remodeling across organs. We previously reported that long-term nacre extract supplementation can delay age-related deterioration when initiated early; however, whether it can provide benefit under post-onset intervention conditions remains unclear. Here, we evaluated a water-soluble nacre extract derived from Pinctada fucata using (i) senescence-accelerated mouse prone 8 (SAMP8) mice and (ii) a D-galactose–induced aging paradigm, with treatment administered after the emergence of age-related phenotypes. In SAMP8 mice, nacre extract improved cognitive and neuromuscular performance, including Y-maze spontaneous alternation, novel object recognition, and forelimb grip strength, and showed a partial improvement in composite aging indices. These benefits were accompanied by reduced senescence-associated markers (p16, p21, and phosphorylated histone H2AX (γH2AX)) in skeletal muscle and peripheral organs, suppression of inflammation-associated signaling in skeletal muscle, and improved redox-related marker profiles. Nacre extract also increased satellite cell– and contractile marker–related immunoreactivity in aged skeletal muscle, suggesting improved regeneration- and maturation-related tissue characteristics. In the D-galactose model, nacre extract was introduced after impairments emerged and administered during the final 11 weeks of continued D-galactose exposure; under these post-onset intervention conditions, nacre extract improved grip strength, showed trends toward improved cognitive performance, and reduced senescence-associated markers in skeletal muscle and adipose tissue, supporting reproducibility across paradigms. Collectively, these findings indicate that nacre extract attenuates aging-associated functional and tissue alterations under post-onset intervention conditions by attenuating senescence- and inflammation-associated tissue responses and improving organism-level homeostasis.