基于端粒保护机制的深海鱼油n-3多不饱和脂肪酸延缓衰老作用研究

天然产物延缓衰老的作用机制研究一直是生命科学领域的关注热点。本项目依托诺贝尔生理学或医学奖获奖成果- - 染色体的端粒保护机制为背景，旨在以深海鱼油n-3多不饱和脂肪酸（PUFA）为对象，系统研究其延缓衰老的作用及端粒保护机制。采用D-半乳糖致衰老小鼠模型，研究n-3 PUFA调节体内氧化还原状态、调控端粒酶活性和提高机体免疫功能的作用；通过研究n-3 PUFA对端粒长度的保护作用，以及对小鼠端粒酶逆转录酶（mTERT）、c-myc和p53基因的调控作用，深入论证其端粒保护作用机制；采用端粒酶缺陷型（mTerc-/-）小鼠模型，通过研究n-3 PUFA对因端粒酶缺陷而分泌的四种特殊蛋白表达水平的影响，探索其对衰老预报因子的调控机制。相关成果为基于端粒保护机制的延缓衰老作用研究奠定理论基础，对拓展深海鱼油功能性食品的新用途，促进海洋生物资源的开发利用，以及推动国家"科技兴海"战略具有重要意义。

Studies on the anti-aging effect of natural products and its mechanism always attract wide attention in the field of life sciences. This project will systematically study the anti-aging effect of n-3 polyunsaturated fatty acids (n-3 PUFA) of marine fish oil and their telomere protection mechanisms based on the achievement of chromosome telomere protection mechanism awarded by Nobel Prize in Physiology or Medicine. The specific aims are to: (i) study the effect of n-3 PUFA on the adjustment of in vivo redox status, regulation of telomerase activity and improvement of immune function in D-galactose-induced aging mice; (ii) investigate the protective effect of n-3 PUFA on telomere length and their regulative effect on mouse telomerase reverse transcriptase (mTERT), c-myc and p53 genes, and thus demonstrate the telomere protection mechanism of n-3 PUFA in aging mice; (iii) study the effect of n-3 PUFA on the expression of four telomerase deficient dependent specific proteins, and thus reveal the regulative mechanism for aging biomarkers in telomerase-deficient (mTerc-/-) mice. The outcomes of this project will significantly be benefit for: (i) establishing theoretical basis for anti-aging study based on telomere protection mechanism; (ii) expanding the use of marine functional food; (iii) facilitating the development and utilization of marine bioresources; and (iv) promoting national strategy of developing marine economy with science and technology.