健康衰老的演化与机制——面向未来的精准营养干预

工程（英文） ›› 2024, Vol. 42 ›› Issue (11) : 1 -2. DOI: 10.1016/j.eng.2024.10.001

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任发政 ^a ,
王晓斌 ^b ,
方冰 ^a

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The Evolution and Mechanisms of Healthy Aging: Future Precision Nutrition Intervention

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全球人口老龄化进程日益加快，如何延长人类寿命，尤其是健康寿命，已成为国内外研究的焦点。随着年龄的增长，人体各组织和器官的结构与功能将相继发生不同程度的退化，其衰老速率与表现形式亦存在差异。这种生理性衰退是老年人机体抵抗力减弱的根本原因，使其更易罹患感染性疾病和多种慢性病。尽管目前已有研究提出了衰老的十二大标志，并借助多种前沿技术绘制出衰老的细胞图谱，但学界尚未全面厘清特定器官的衰老特征及分子机制，亦未明确不同组织器官之间的相互作用模式，影响了精准抗衰干预策略的实施。

营养干预是改善和维持机体健康状况的重要手段，其干预效果的关键在于靶点的精准性，这也推动了“精准营养”这一概念的提出与逐步完善。在健康领域，“精准”这一理念最早出现在医学上，指根据患者的具体情况量身定制治疗方案，即根据特定症状提供适当剂量的有效物质。在营养领域，秉承预防医学理念，通过营养干预维持机体健康指标已成为促进健康的重要途径。因此，厘清自然衰老过程中关键器官及核心功能的变化并深入理解其内在驱动因素，是实现精准干预的前提条件。同时，阐明特定人群中特定营养素或功能因子的作用及机制，则构成有效营养干预的基础。

精准营养这一概念的提出为流行病学研究，特别是营养流行病学，带来了新的机遇与挑战。例如，由于中国人群叶酸利用关键酶基因位点突变率较高，与此相关的同型半胱氨酸代谢异常，即便在高血压得到有效控制的情况下，其血液中高同型半胱氨酸水平仍会增加脑卒中风险。针对这一问题，宋昀等提出并设计了一种适用于中国人群的叶酸与降压药物联合使用的治疗方案，实现了针对中国人群基因多态性的精准用药。基于此前沿进展，本刊特别策划了本期“精准营养与健康”专题，重点聚焦自然衰老过程中关键器官和功能的衰退机制以及营养素和功能因子改善健康的主要作用机制研究。

营养素在不同人群中的生物学功能各不相同，功能因子的活性也有其精确的作用机制。在本期专题文章中，韩天澍等总结了特定营养素在调节代谢和免疫功能中的关键作用，并指出个体对特定营养素可能存在不同的响应方式，为制定精准有效的营养干预方案奠定了基础。安鹏等分析了不同人群补充维生素D后在血压、血脂和血糖水平的心血管代谢调节方面的不同效应。王希璠等则证明了葡萄籽提取物原花青素C1（PCC1）通过促进肠道微生物分泌戊酸，调控肠上皮细胞的自噬过程并促进黏液的分泌，从而缓解炎症性肠病。林莹莹等聚焦在老年人、肠道疾病患者以及术后病患的肠道修复中起着关键作用的肠道干细胞，研究了肠道干细胞中的微小RNA（如miR-29a和miR-29b），它们通过靶向抑制Hnf4g表达，进而阻断脂肪酸氧化介导的氧化磷酸化过程，促进组织再生。

机体的免疫功能、肺和肠道组织在衰老过程中各自呈现出独特的衰老模式；它们的衰老特征及其背后的驱动因素也各不相同。在本期专题文章中，吴建民等指出，衰老时骨髓会产生更多的多形核髓系来源的抑制性细胞（PMN-MDSC），这些细胞会流向肠道等器官，影响其免疫功能，这也是导致老年人容易感染艰难梭菌的主要原因。全蕊等揭示了与衰老相关的肺纤维化机制，衰老的肺泡Ⅱ型祖细胞（AT2）通过分泌纤溶酶原激活物抑制因子-1（PAI-1），直接与成纤维细胞相互作用，促进Ⅰ型胶原蛋白（Col I）合成，加速肺纤维化的进程。宋蕊等明确了衰老对肠道中蛋白质消化与吸收的影响，并发现L型氨基酸转运蛋白2（LAT2）在蛋白质利用率下降中发挥关键作用。于守娟等评估了年轻小鼠的粪便微生物群移植对衰老小鼠皮肤更新的影响，发现其作用机制主要是通过增加乳酸菌和乳球菌的丰度以及提高色氨酸及其代谢物的水平。

未来，关于衰老驱动因素、疾病发生与发展以及特定营养素在这些过程中的作用的研究将推动精准营养与健康工程的发展，并在实现健康改善的营养干预方面发挥重要作用。