全球人口老龄化正在以前所未有的速度推进。预计到2050年,全球老年人口规模将持续快速增长[1]。老龄化在延长人均寿命的同时,也显著增加了慢性非传染性疾病的负担。健康衰老,即在整个生命周期中避免或延缓慢性疾病的发生,已成为全球公共卫生的核心目标[2]。

近年来,慢性低度炎症被认为是连接衰老进程与多种衰老相关疾病的重要病理基础[3]。其中,由营养过剩、脂质代谢紊乱和胰岛素抵抗等代谢应激驱动的炎症状态被称为代谢性炎症[4]。不同于急性炎症,其通常表现为肿瘤坏死因子α(tumor necrosis factor-alpha, TNF-α)、白细胞介素1β(interleukin-1 beta, IL-1β)和C反应蛋白(C-reactive protein, CRP)等促炎标志物水平轻度但持续升高[3]。代谢性炎症可视为营养和代谢因素失衡驱动的慢性炎症,无明显临床症状,却能通过激活TLR4/NF-κB通路[4]、活化NLRP3炎症小体[5]、增加氧化应激[6]、诱导线粒体功能障碍[3]及加剧营养感应异常等途径,长期损害组织功能,驱动动脉粥样硬化、胰岛素抵抗及神经退行性病变,最终导致心血管疾病、2型糖尿病、代谢功能障碍相关脂肪性肝病以及阿尔茨海默病等衰老相关性疾病。

传统临床管理聚焦衰老相关疾病确诊后的疾病终末期,此时组织损伤往往已不可逆[7]。而采用早期营养干预,将干预窗口前移至无症状的代谢性炎症阶段,具有更广阔的应用前景[7]。研究表明,膳食等环境因素在调控老年人群代谢性炎症中发挥关键作用[7-8]。大规模队列研究表明,地中海饮食、DASH饮食(dietary approaches to stop hypertension,得舒饮食)等优质膳食模式,可有效降低机体炎症水平[8-9]。然而,目前研究仍存在不足:机制研究多集中于疾病治疗阶段,针对早期预防的探索不足[10];人体临床证据相对缺乏,尤其是老年人群[11];对特定营养素在不同状态下的作用差异认识不清[12-13];以及多组学研究结果难以转化为适老食品功能配料的创制依据与应用策略,是该领域从基础研究走向产业转化的重要瓶颈。

本文围绕老年代谢性炎症的发生特点与评价方法,重点介绍早期营养干预的作用机制及典型食物成分的老年人群循证依据,并进一步讨论适老食品功能配料的靶向筛选、稳态化与递送、适老化应用及评价,旨在为面向健康衰老的精准营养干预研究和适老功能食品产业的高质量发展提供参考。

1 老年代谢性炎症的发生特征与评价方法

老年代谢性炎症是免疫系统重塑,机体慢性低度炎症水平升高与免疫应答能力减弱共同作用的结果。核心特征体现在4个方面:一是老年阶段的低度炎症更易维持和迁延[14];二是机体对营养和代谢负荷适应能力降低,使餐后代谢扰动更易伴随持续的炎症应答[15];三是老年代谢性炎症还具有明显的多系统性和个体差异性[16];四是老年代谢性炎症通常呈低幅度、长期性和动态演变的特点,并可早于临床疾病发生[17]。

准确评价老年代谢性炎症是开展早期营养干预的前提。传统研究常使用CRP、IL-6、TNF-α等炎症指标,能够直观反映系统性炎症负荷水平[10]。但是,单一炎症因子难以全面反映老年代谢性炎症的复杂性[18]。

为弥补传统方法的不足,研究者发展了多种互补的评价技术(表1[19-29])。

膳食炎症指数(dietary inflammatory index, DII)是基于文献衍生的评分系统,可量化个体饮食相关的炎症暴露[19]。较高的DII评分与CRP升高显著相关[20]。中国膳食炎症指数(China dietary inflammatory index, CHINA-DII)考虑了中西方膳食结构的差异,保留了27种膳食成分,临床样本显示,该指数与hs-CRP呈正相关(r=0.20,P≤0.001),高CHINA-DII评分个体出现hs-CRP≥3 mg/L的可能性是低评分个体的1.90倍[21]。多组学技术可把炎症与营养、肠道微生物、脂质重塑和能量代谢异常关联起来,为老年代谢综合征的深度表型和未来临床转化提供了依据[22-23]。

此外,新型生物标志物[24-25]、影像学与人工智能技术[25-29]可从分子机制、器官结构与多源数据整合层面补充评价维度,更好地支持老年代谢性炎症的早期识别和精准营养干预。

2 老年代谢性炎症的早期营养干预机制

老年代谢性炎症是长期膳食暴露与衰老相关代谢弹性下降共同作用的结果。随着年龄增长,机体对餐后葡萄糖、脂质等营养底物的处置能力减弱,代谢恢复时间延长;同时,老年人肌量减少、肠屏障完整性受损、线粒体功能下降及免疫调节失衡等,会进一步削弱机体对营养负荷的缓冲能力和炎症消退能力。反复或过度的餐后营养应激更易累积为持续性低度炎症反应,推动代谢异常与炎症激活相互促进[30]。基于此,早期营养干预应从5个层面展开(图1)。

2.1 干预消化吸收过程

消化吸收决定营养底物进入循环的速度和持续时间。老年人餐后底物清除减慢,表现为葡萄糖动力学受抑和餐后甘油三酯暴露增加,在同等高糖或高脂膳食负荷下,老年人更易形成持续的高糖、高脂代谢暴露[31]。葡萄糖快速入血可增加活性氧(reactive oxygen species, ROS)和非酶糖化,促进晚期糖基化终末产物(advanced glycation end products, AGEs)累积,并经晚期糖基化终末产物受体(receptor for advanced glycation end products, RAGE)放大NF-κB信号[32]。因此,老年人早期营养干预过程可通过研发能保留完整食物基质、增加黏性或可发酵膳食纤维、限制游离糖及超加工比例的适老食品,来延缓胃排空和淀粉水解,削平餐后葡萄糖-胰岛素峰值,从源头减少ROS、AGEs-RAGE及NLRP3/NF-κB信号通路相关的营养过载。

人群干预研究为消化吸收过程干预提供了多层面的证据。花青素随高脂高能量餐摄入,可改善超重老年人餐后大血管及微血管反应,并降低4 h的CRP水平[33];健康老年人随机交叉试验显示,乳清蛋白/瓜尔胶餐前预负荷可降低葡萄糖负荷后的血糖和3-O-甲基葡萄糖反应,其作用主要与延缓小肠葡萄糖吸收和促进胰岛素分泌有关[34]。抗性淀粉补充研究也显示,每天补充30 g抗性淀粉可改善70岁以上老年人的血糖、胰岛素和稳态模型评估的胰岛素抵抗指数(homeostatic model assessment of insulin resistance, HOMA-IR)[35]。膳食加工水平方面,一项纳入36名社区老年人的随机交叉受控膳食干预试验,将受试者日常习惯膳食中约50%能量来自超加工食品的模式,替换为仅约13%能量来自超加工食品且符合膳食指南的低超加工膳食,干预持续8周。结果显示,降低超加工食品比例可降低能量摄入,使体重和脂肪量下降,并改善HOMA-IR、胰岛素、C肽、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)、载脂蛋白B和CRP水平;同时下调瘦素表达、上调成纤维细胞生长因子21表达,表明在老年人中降低超加工食品比例并提高整体膳食质量,可通过能量摄入和营养感知网络减轻老年人的代谢炎症负荷[36]。肠道层面,可将可发酵膳食纤维与n-3多不饱和脂肪酸(n-3 polyunsatura-ted fatty acids, n-3 PUFAs)或益生菌联合应用,老年低度炎症人群补充后,血清戊酸和IL-10水平升高[37];在50～75岁人群中,可溶性玉米纤维联合鱼油可改变肠道菌群β多样性及肠上皮转录网络[38]。消化吸收过程干预可通过保留食物基质、延缓糖脂底物吸收、降低超加工食品比例、增加可发酵底物和优化n-3 PUFAs供给等多环节,协同降低老年人餐后糖脂代谢负荷,并改善与低度炎症相关的肠道微生态和营养感知网络。

2.2 调节食物与肠道菌群相互作用

肠道菌群将膳食底物转化为短链脂肪酸(short-chain fatty acids, SCFAs)、吲哚类等活性信号,是膳食调控老年代谢性炎症的核心靶点[39]。衰老和虚弱主要改变菌群功能,不同队列中菌属变化虽有差异,但功能层面的共性在于可发酵底物利用能力和屏障支持能力下降[39],导致结肠上皮能量不足、紧密连接松解,脂多糖(lipopolysaccharide, LPS)易位后经TLR4/NF-κB和NLRP3通路将肠源性刺激传递至肝脏、脂肪和骨骼肌[40]。因此,早期干预应定向调节“底物-代谢物-屏障-组织代谢”链条,而非仅增加某一菌属。

临床研究为此提供了多维证据。MaPLE试验显示,富多酚膳食可增加瘤胃球菌科(Ruminococcaceae)并降低血清连蛋白水平,表明多酚经菌群代谢可改善肠道屏障功能[41-42]。该效应与菌群代谢物吲哚-3-丙酸升高耦联,而多酚的变化又与CRP降低显著相关,说明屏障修复与全身炎症缓解同步发生[42]。老年代谢综合征人群的研究发现,较低的膳食炎症指数与更高的菌群多样性及更稳定的粪便代谢网络相关,进一步支持膳食-菌群-炎症轴的存在[43]。短期高剂量燕麦干预可提高丁酸、降低连蛋白,且两者变化与菌群位移直接相关,表明可发酵纤维对屏障功能的即时影响[44]。菌株干预方面,含植物乳杆菌(L. plantarum)PBS067、嗜酸乳杆菌(L. acidophilus)PBS066和罗伊氏粘液乳杆菌(L. reuteri)PBS072的合生元,在老年代谢综合征患者中连续服用60 d可显著改善胰岛素敏感性和血脂谱[45];而益生菌对卡塔菌属(Catabacter)、伯克霍尔德菌属(Burkholderia)、脂多糖结合蛋白及单核/树突细胞的调节存在性别差异性,提示干预时需考虑个体因素[46]。此外,在年龄为63岁及以上且基线阿克曼菌丰度较低的亚组中,巴氏灭活嗜黏蛋白阿克曼菌(A. muciniphila)MucT可提高肝胰岛素敏感性和餐后胰高血糖素样肽1反应,说明后生元亦可通过特定菌株依赖通路发挥效应[47]。据此,用于调节食物与肠道菌群的适老食品应优先选择能产生明确功能代谢物并同步维护肠屏障与组织代谢稳态的组合,并依据代谢通量、通透性和菌群丰度进行动态评估。

2.3 参与细胞生化反应

营养素吸收后进入细胞代谢网络,参与氧化磷酸化、谷胱甘肽循环和脂质氧化等反应。衰老使线粒体质量控制减弱,过量葡萄糖和脂肪酸更易引起ROS积累、脂质过氧化和蛋白糖化,进而形成代谢损伤与炎症相互放大的恶性循环。

针对特定生化瓶颈的营养补充可能有助于恢复细胞稳态,但其作用具有明显的靶点依赖性。烟酰胺核糖可扩增老年男性骨骼肌NAD+代谢组,并诱导抗炎转录特征,但未显著改善骨骼肌线粒体生物能学和整体代谢功能[48]。甘氨酸和N-乙酰半胱氨酸(N-acetylcysteine, NAC)联合补充,为谷胱甘肽合成提供底物,在老年人中可改善谷胱甘肽不足、氧化应激、线粒体功能、炎症状态及胰岛素抵抗[49]。尿石素A作为肠道菌群来源的食物代谢物,可改善部分肌肉耐力,并降低与线粒体代谢和炎症相关的血浆标志物,但对6 min步行距离和最大ATP生成能力的改善未达到显著水平[50]。硒与辅酶Q10联合补充可提高低硒老年人的血清游离巯基水平,从而改善全身氧化还原状态[51]。因此,此类干预不宜作为泛化的“抗衰老补充”,而应基于缺乏状态、氧化还原失衡或线粒体代谢障碍等具体问题进行精准干预。

2.4 调控炎症信号通路

营养应激可经模式识别和氧化还原通路转化为炎症输出。LPS、氧化脂质及损伤相关分子可激活TLR4/NF-κB,促进TNF-α和IL-6表达[52]。线粒体ROS和脂质沉积还可激活NLRP3炎症小体,促进IL-1β和IL-18成熟,加重老年低度炎症和功能衰退[5]。

不同营养干预对炎症信号通路的调节具有明显的细胞类型、组织部位和剂量依赖性。富橄榄油地中海膳食可调节高心血管风险老年人外周血单个核细胞(peripheral blood mononuclear cells, PBMCs)中CDKN2A、IFNG、NLRP3、PIK3CB和TGFB2等炎症及神经炎症相关基因表达[53]。燕麦酚酰胺可抑制绝经后女性单个核细胞NF-κB结合活性[54]。白藜芦醇在老年2型糖尿病患者中可提高沉默信息调节因子1水平并改善部分氧化应激指标[55]。在维生素D缺乏老年人中,高剂量维生素D单独干预或与NAC联用可下调PBMCs中p16表达并降低衰老相关β-半乳糖苷酶活性[56]。然而,单一营养素并不必然带来预期的信号通路改变。n-3 PUFAs联合抗阻训练虽可改善部分肌力指标,但未进一步增强抗阻训练对骨骼肌p65 NF-κB等炎症或分解代谢信号的调节作用[57];线粒体靶向抗氧化剂MitoQ虽降低老年人骨骼肌线粒体H2O2释放能力,却未改变运动后AMPK、p38 MAPK或ERK1/2磷酸化及相关基因应答[58];萝卜硫素在老年人PBMCs离体处理条件下可增强核因子E2相关因子2(nuclear factor erythroid 2-related factor 2, Nrf2)及其下游抗氧化基因表达,但该结果无法直接外推为口服干预效果[59]。

2.5 作为细胞和组织组成成分

部分营养素可进入细胞膜和肌肉组织,影响炎症消退、底物利用和组织修复能力。二十碳五烯酸(eicosapentaenoic acid, EPA)和二十二碳六烯酸(docosahexaenoic acid, DHA)进入膜磷脂后,可改变花生四烯酸底物池,并为消退素和保护素等促消退介质提供前体[60]。动物研究显示,老龄骨骼肌存在促消退脂质介质合成不足,补充消退素D1(resolvin D1, RvD1)可降低炎症因子表达、限制纤维化并改善损伤后肌力恢复,但其对免疫细胞浸润和肌纤维再生的作用有限[61]。n-3 PUFAs可增强老年骨骼肌对氨基酸和胰岛素的合成反应[62],长期补充还可能增加健康老年人的肌肉量和力量[63]。在肌少症老年人中,亮氨酸强化乳清蛋白联合维生素D可减缓IL-6随时间升高的趋势,但并非直接降低IL-6水平[64]。蛋白质、维生素D和β-羟基-β-甲基丁酸(beta-hydroxy-beta-methylbutyrate, HMB)强化补充可降低营养不良肌少症老年人的铁蛋白和骨桥蛋白[65],而在营养状况良好的老年人中,亮氨酸强化蛋白单独或联合n-3 PUFAs干预并未进一步改善肌量、肌力、身体功能或肌蛋白合成率,表明其效应受基线营养状态和肌肉合成阻力影响[66]。上述部分营养素干预可补足细胞功能物质,阻断氧化损伤向代谢性炎症转化。

3 典型食物成分对老年代谢性炎症的调控效应与循证

不同食物成分对老年代谢性炎症的调控效应差异显著,其作用强度、作用机制各不相同。为便于系统比较与整体把握,本文分别讨论各类食物成分在老年代谢性炎症调控中的作用特点及其作为适老食品功能配料的应用依据。表2汇总了典型膳食成分对老年代谢性炎症调控的人群证据[37,64,67-88]。

3.1 膳食碳水化合物

碳水化合物的抗炎效应差异,主要体现在可消化速度、发酵特性及食物结构的完整性上。对美国老年队列的分析显示,总膳食纤维每日摄入量每增加5 g,CRP和白细胞介素1受体拮抗剂(interleukin-1 receptorCFU,菌落形成单位;CI,置信区间;CRP,C反应蛋白;DBPC-CO-RCT,双盲、安慰剂对照、交叉随机对照试验;DBPC-P-RCT,双盲、安慰剂对照、平行组随机对照试验;DBPC-RCT,双盲、安慰剂对照随机对照试验;DHA,二十二碳六烯酸;EPA,二十碳五烯酸;FFAR2/3,游离脂肪酸受体2/3;hs-CRP,高敏C反应蛋白;IFN-γ,干扰素γ;IGF-1,胰岛素样生长因子1;IL,白细胞介素;IL-1RA,白细胞介素1受体拮抗剂;ITT,意向性治疗分析;LDL-C,低密度脂蛋白胆固醇;LPS,脂多糖;MAPK,丝裂原活化蛋白激酶;mTORC1,哺乳动物雷帕霉素靶蛋白复合物1;NF-κB,核因子κB;Nrf2,核因子E2相关因子2;P-RCT,平行组随机对照试验;PCS,前瞻性队列研究;PUFA,多不饱和脂肪酸;ROS,活性氧;SAIS,单臂干预研究;SCFAs,短链脂肪酸;SD,标准差;TLR4,Toll样受体4;TNF-α,肿瘤坏死因子α;Treg,调节性T细胞;VDR,维生素D受体。

antagonist, IL-1RA)均呈小幅下降趋势,其中与谷物纤维的关联最为稳定[69]。然而,纤维的“抗炎推定”并不能一概而论。在针对老年人的随机试验中,燕麦β-葡聚糖或小麦阿拉伯木聚糖干预6周时,并未显著改善老年人肠通透性、菌群组成或全身炎症水平[71];洋车前子壳纤维对CRP、IL-6等指标的总体效应同样不显著[72]。这提示,适老配方不能仅依据膳食纤维总量来推定抗炎效应,还需细致区分其黏度、可发酵性、聚合度及个体耐受性。

菊粉、抗性糊精和抗性淀粉等可抵抗小肠消化,在结肠发酵产生SCFAs,进而影响肠屏障和免疫代谢。老年2型糖尿病患者连续12周摄入菊粉与抗性糊精强化奶粉后,空腹及餐后血糖和胰岛素抵抗指数均显著下降[67]。以老年人粪便开展的体外发酵研究还发现,菊粉与抗性糊精复配较单一菊粉产气更少,提示复配可能改善胃肠耐受性,但该结果尚不能替代人体临床验证[68]。此外,挤压麦麸虽可提高血清SCFAs,却未同步改善心理和生理功能相关结局[70],进一步说明发酵产物升高与临床获益并非同义。

需要指出的是,血糖生成指数(glycemic index, GI)无法全面表征膳食炎症调控效应是碳水化合物干预中的重要共识。GI主要反映血糖升高速度,但不能充分评价肝脏脂肪新生、肠道发酵、内毒素生成及食物基质效应[89]。例如,果糖属于低GI碳水来源[90],但大量摄入果糖仍可促进肝脏脂质合成、诱发内毒素血症[91-92]。相比之下,全谷物富含膳食纤维、抗氧化物和植物化学物,在部分随机对照试验(randomized controlled trial, RCT)中可降低炎症标志物[93];RCT荟萃分析显示,豆类摄入可降低CRP/hs-CRP水平,且该效应在特定亚组中更为显著[94]。因此,适老食品中碳水化合物设计应综合考虑糖类型、聚合度、糖苷键类型、加工方式及摄入时间。

3.2 膳食蛋白质、氨基酸

老年人需足量优质蛋白以维持肌肉和免疫功能,但蛋白质的抗炎效应往往不能脱离整体干预组合来单独归因。肌少症老年人在运动基础上补充乳清蛋白、必需氨基酸和维生素D,不仅改善去脂体重和握力,CRP亦见下降[73];在PROVIDE研究中,亮氨酸强化乳清蛋白与维生素D干预使IL-6在13周内保持稳定,而对照组则升高[64]。但现有研究仅能佐证复合营养干预可缓冲肌少症相关低度炎症,却不能证明亮氨酸单独具有同等抗炎效应。亮氨酸长期补充虽可改善蛋白质合成[75],其剂量设计仍应结合总蛋白摄入、肾功能及活动水平综合考量。

老年蛋白质干预还需区分肌肉合成获益与炎症下降之间的因果关系。健康老年男性早餐补充维生素D和亮氨酸强化乳清饮品,可提高餐后肌蛋白合成效率[74],但该研究并未证实其对全身炎症的改善效应。对于肌少症患者,肌量恢复可减少失能和代谢负担,从而间接影响慢性炎症,但仍需以CRP、IL-6等直接指标加以验证。因此,适老高蛋白产品的评价终点应同时覆盖摄入量、肌肉功能、肾脏耐受性与炎症标志物。

蛋白质来源还会通过伴随营养素和菌群代谢影响炎症。在2型糖尿病患者中,植物蛋白和动物蛋白等高蛋白饮食均能降低趋化素和颗粒蛋白前体,但IL-6与TNF-α水平未显著改变,说明“植物蛋白必然抗炎、动物蛋白必然促炎”的二分法并不成立[76]。增加植物蛋白来源可改变心代谢高风险人群的菌群组成和色氨酸代谢[77],为“蛋白质来源-菌群代谢物-免疫调节”提供了人体依据,但其长期炎症结局仍需进一步验证。适老食品宜以乳、蛋、鱼和豆类构成多样化蛋白来源,控制加工红肉及其伴随的饱和脂肪、血红素铁和AGEs,同时避免将体外或动物研究中的活性肽机制直接等同于临床疗效。

3.3 膳食脂质

对于老年人,过度低脂可能影响能量摄入、脂溶性维生素吸收及食品适口性,不利于老年代谢性炎症管理。因此,适老脂质营养干预的核心在于脂肪酸的替代关系,而非简单降低总脂肪。超重、久坐的中老年人补充EPA与DHA 4个月后,IL-6炎症水平较安慰剂明显下降[78];慢性炎症人群的交叉试验证实,EPA和DHA对单核细胞炎症反应及血浆促炎症消退介质产生不同影响,表明两者抗炎功能不能完全互换[79]。含n-3 PUFAs及维生素的强化乳可改善部分炎症衰老指标[80],但多成分配方难以将效应归因于某一活性成分。

较低剂量n-3 PUFAs与多菌株益生菌联用8周,并未显著改善老年人的主要终点hs-CRP水平,但IL-10、粪便戊酸水平和n-6/n-3比值出现有利变化[37]。值得关注的是,2型糖尿病患者补充n-3 PUFAs可上调Nrf2表达并改善抗氧化状态[81],为氧化应激与炎症联动提供了人体线索。适老脂质配方应优先以EPA、DHA和单不饱和脂肪酸替代反式脂肪与过量饱和脂肪,并明确实际剂量及氧化稳定性;对于合并抗凝治疗、吞咽障碍或能量摄入不足者,还需兼顾用药风险、产品质构和能量密度。

3.4 膳食植物化学素

植物化学素主要通过调节氧化还原稳态、内皮功能和炎症信号发挥老年代谢性炎症调控作用,但其临床效应具有剂量、人群和性别特异性。轻度认知障碍或心血管代谢异常的中老年人补充花青素24周后,CRP、IL-6和IL-1β水平显著低于安慰剂组[82];花青素饮料还可影响外周淋巴细胞Nrf2通路及其下游基因转录[83]。槲皮素的抗炎效应在冠状动脉旁路移植患者中呈现性别异质性,血管功能获益主要见于男性,而整体人群hs-CRP水平仅呈轻微下降趋势[84]。

长期补充可可提取物可使老年人hs-CRP的年变化下降,但干扰素γ并未同向改善,显示单一抗炎评分可能掩盖不同免疫指标的分化反应[85]。针对外周动脉疾病患者的研究进一步显示,可可黄烷醇可在肌肉组织中诱导Nrf2通路相关变化[86]。植物甾醇作为另一类备受关注的膳食活性物质,其强化发酵乳可在接受他汀治疗的高龄人群中进一步降低LDL-C及胆固醇吸收标志物水平[87],其直接证据主要集中于降低LDL-C并抑制肠道胆固醇吸收,而非直接的抗炎作用。此外,对于植物甾醇等脂溶性成分,其降低胆固醇吸收的作用还会受到食品基质、添加形式及摄入方式等因素的影响,这些因素可能进一步影响活性成分的释放和吸收[88]。

4 适老食品功能配料的创制路径与应用评价

4.1 功能配料的筛选与转化特征

适老食品功能配料创制需在功效证据与食品转化属性之间建立联系。针对老年代谢性炎症持续性、低度和多系统累及的特点[3],候选配料既应对应血脂与脂质吸收、肠道菌群与屏障调节、炎症信号及肌肉营养调控等关键环节,也需兼顾有效剂量、加工稳定性、生物可及性和食品基质适配性。因此,第3节中的活性食物成分并非均可直接转化为适老食品功能配料。

从功能基础和食品转化特征来看,可发酵膳食纤维和抗性淀粉可经肠道菌群发酵产生SCFAs,参与肠屏障和免疫稳态调节[95],具有较好的食品应用基础。可发酵膳食纤维和抗性淀粉类产品开发需兼顾功能剂量、产品质构和老年人群胃肠耐受性。膳食蛋白质、氨基酸及活性肽兼具营养补充和代谢调节价值,其中植物蛋白可满足老年人维持肌肉健康的营养需求[96];活性肽虽具有潜在生物活性,但其苦味、胃肠稳定性和吸收效率等问题仍制约其口服应用[97]。n-3 PUFAs可参与炎症相关脂质介质生成和细胞炎症信号调节[98-99],但其高度不饱和结构在产业应用中易受氧化稳定性及体系相容性的限制。植物多酚、植物甾醇等植物化学素结构和功能多样,但部分成分存在溶解性差、稳定性弱或生物利用度不足等缺点。因此,不同功能配料的开发重点并不相同,其中植物化学素更能体现活性成分由功能发现向结构优化、稳态化改良和食品应用转化的技术需求。

在植物化学素中,植物甾醇和黄酮类成分分别代表具有不同理化特征和转化需求的功能因子。植物甾醇可通过抑制肠道胆固醇吸收,降低LDL-C水平,其人体证据主要集中于血脂管理[100];特定植物甾醇有机酸酯在TNF-α诱导的细胞模型中表现出抗炎和改善线粒体相关功能的潜力[101]。竹叶黄酮具有清除自由基、抗炎、调节脂代谢等多重功能,可通过修复肠道屏障、抑制促炎细胞因子、重塑肠道菌群等方式改善老年个体的炎症状态[102-103]。此外,MaPLE随机交叉试验显示,富含多酚的膳食可降低肠通透性,升高老年人的血清和粪便钙卫蛋白水平,并使相关炎症和肠屏障标志物呈现协同变化[104],为多酚类功能配料在老年代谢性炎症干预中的应用提供了人群依据。因此,植物甾醇和竹叶黄酮既具有与代谢性炎症相关的功能基础,又分别面临脂溶性成分分散稳定性和多酚类成分稳定性差、生物利用度不足等转化问题,可作为后续稳态化改性、靶向递送及适老食品应用研究的代表性配料。

4.2 功能配料的稳态化与递送设计

许多植物功能配料存在溶解性差、易氧化、消化释放不足等问题,这是限制其在适老食品中应用的重要原因[105-107]。据此,针对不同植物化学素的结构和稳定性特点进行稳态化与递送设计,是其由活性成分向适老食品功能配料转化的关键。

稳态化策略主要包括酯化改性、乳液递送、微胶囊化、纳米包埋、蛋白-多糖复合载体组装、环糊精包合和固体分散体系制备等[108]。植物甾醇可通过结构修饰改善油相或水相相容性,但改性后仍需验证其降胆固醇活性与安全性[109]。在O/W乳液中,乳清分离蛋白或大豆分离蛋白形成的界面膜可延缓植物甾醇光氧化[110]。植物甾醇与乳清分离蛋白可通过疏水作用和氢键形成自组装复合物;质量比为1∶5的甾醇/蛋白质复合物氢键作用最强、包封率最高,且其蛋白质二级结构与氢键强度共同影响活性成分的释放和生物可及性[111]。竹叶黄酮等黄酮类化合物则通过酶法酰化提升脂溶性与稳定性,如在Novozym 435催化下,于C6-OH位点引入芳香酰基,可提高脂溶性并增强其在油脂体系中抑制脂质过氧化的能力[112]。

递送体系设计需兼顾老年胃肠道在消化液分泌、胃排空、肠道运动及吸收功能等方面的变化[113]。例如,植物甾醇/乳清分离蛋白自组装复合物在体外模拟消化中的释放率为98.44%,高于游离植物甾醇的12.65%,说明蛋白载体具有提高生物可及性的潜力[111]。但在适老食品开发中,该结果不能替代人群证据,仅可用于优化适老食品配料的剂型、剂量和评价终点,从而将“稳定化-释放-吸收-功能效应”连成可检验的递送链条。

4.3 功能配料的适老化应用与多维评价

适老食品功能配料的应用不能仅取决于其体外活性,还应综合考虑食品基质适配性、加工稳定性、生物可及性、感官接受度和长期食用安全性。老年人常伴随咀嚼吞咽能力下降、胃肠耐受性降低、味觉敏感性改变和慢病共存等特点,因此功能配料应用于适老食品时,应兼顾营养密度、质构安全性、风味温和性、剂量合理性和慢病适宜性。

应用层面,植物化学素进入实际食品体系后,其利用程度不仅取决于活性成分添加量,还受到食品基质组成、加工方式及消化释放行为的共同影响。以姜黄素类为模型的研究显示,不同食品基质及纤维配方对其体外口服生物可及性的影响并不一致[114],表明植物化学素的适老化应用需要将配料特性与食品载体协同设计。具体而言,植物甾醇适合用于乳制品、植物基饮品和营养粉等体系,其功能定位宜聚焦辅助血脂管理;结构修饰可改善其体系相容性[109],蛋白复合可提高其体外消化释放效率[111]。竹叶黄酮与淀粉、魔芋葡甘聚糖复配并经动态高压微射流处理后,可改变复合体系的流变性、结构和体外消化特性,为低消化速率主食或代餐设计提供工艺依据[115];酰化改性则有助于拓展竹叶黄酮在油脂或乳化食品中的应用[112]。此外,普鲁兰酶辅助竹叶黄酮可改善山药粉的冲调性能并调节其体外消化行为[116]。除植物化学素外,膳食纤维、益生元和抗性淀粉可通过发酵产物参与肠屏障与免疫稳态调节,但产品评价应区分一般肠道健康效应与老年代谢性炎症终点[95]。n-3 PUFAs可用于心血管相关营养设计,但需同时控制氧化风险、能量密度及适用人群,其抗炎价值不能仅凭成分添加量推断[98]。

为此,适老食品功能配料的评价不能停留在成分含量检测层面,而应建立多维度评价体系。一方面,应检测功能配料在加工、贮藏和消化过程中的保留率、氧化产物、生物可及性和释放行为;另一方面,人群研究应预先界定主要终点,结合血脂、餐后血糖、CRP或IL-6等炎症指标、胃肠耐受性、膳食依从性和生活质量指标开展验证。总体而言,适老食品功能配料的转化路径应遵循靶向筛选、稳态递送、基质协同和适老评价的思路,核心目标不是简单提高活性成分添加量,而是在安全、稳定、可长期食用的基础上,检验真实食品体系对老年代谢性炎症的干预效果。

5 总结与展望

老年代谢性炎症是连接衰老进程与多种慢性疾病的关键病理基础,其本质是多器官代谢异常与免疫反应的持续交互,具有隐匿性、波动性和明显个体差异。早期营养干预将干预窗口前移至无症状的代谢性炎症阶段,可通过调控消化吸收、肠道菌群-膳食互作、细胞生化反应、炎症信号通路及细胞组成等多个层面,改善营养负荷应答、代谢稳态及炎症调节过程,为延缓代谢异常向慢性疾病进展提供潜在干预路径。

针对老年人群的循证研究表明,膳食纤维、抗性淀粉、蛋白质与氨基酸复合营养、n-3多不饱和脂肪酸以及植物甾醇、黄酮类等典型食物成分均可参与炎症与代谢调控,但其实际效应受到干预剂量、基线营养与代谢状态、食品基质及个体差异等因素影响,且部分干预对炎症终点的改善并不显著。因此,不能将机制层面的潜在作用直接等同于临床有效性,仍需以与目标人群和实际食品形态相匹配的人体研究作为功能评价的重要依据。适老食品功能配料的创制与应用也应由单纯追求高纯度、高添加量,转向靶向筛选、稳态递送、基质协同和适老评价相衔接的全链条研发,重点解决溶解性与稳定性不足、生物可及性受限、食品基质适配性差及感官接受度低等问题。

未来研究方向如图2所示。鉴于老年代谢性炎症具有慢性低度、多因素驱动和多靶点调控等特点,功能配料研发需进一步提高活性成分发现效率和功效评价的生理相关性。例如,未来可引入人工智能辅助天然产物研究,利用机器学习和深度学习处理复杂数据,用于候选成分筛选、成分分析及药理机制研究,从而提高早期发现效率;肠道类器官具有多种肠上皮细胞类型,可用于研究膳食营养素与肠道稳态的相互作用;器官芯片则可通过模拟动态微环境补充传统二维培养的不足,为肠道稳态和疾病过程研究提供更接近生理状态的模型。因此,未来应推动计算筛选、类器官或器官芯片验证、动物实验与人群研究之间的逐级验证体系,增强功能配料功效证据的可靠性和转化价值。

在适老食品功能配料制备和产品转化方面,研究重点应由单纯追求活性成分得率转向绿色加工、活性保持与产品适配性的协同优化。超声辅助提取可用于酚类、黄酮等植物活性成分的提取,3D食品打印则为吞咽困难老年人的营养组成和质构定制提供了潜在路径,但均需进一步评价工艺标准化、加工稳定性、食用安全性和规模化可行性。同时,应把感官品质纳入功能配料的早期设计环节,针对多酚的苦涩味和部分生物活性肽的苦味,发展减苦、掩蔽、风味协同与老年人群感官评价方法,使产品不仅具有潜在功能,而且能够被长期接受和持续食用。

面向老年代谢性炎症的适老食品功能配料研究,应逐步形成“多维数智筛选评价-绿色加工与数字化制造-营养感官协同优化”的研发路径。同时加强剂量-效应关系、生物利用度、长期食用安全性及老年人群干预研究,使功能配料的发现、评价与食品应用形成更完整的证据链,推动适老功能食品由实验室研究向安全、有效且具有长期食用可行性的产品转化。

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Early Nutritional Interventions for Metabolic Inflammation in Older Adults and Development of Functional Ingredients for Age-Friendly Foods

Lu Baiyi1,2, Liu Xuanzhuo1, Wang Zhangtie1,2

(1.College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China;2.ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311200, China)

Abstract： Metabolic inflammation in older adults is a chronic low-grade inflammatory state resulting from the combined effects of nutritional imbalance, metabolic abnormalities, immune remodeling, and alterations in the gut microbiota during aging, and constitutes an important pathological basis for age-related diseases such as atherosclerosis, type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and cognitive impairment. Shifting the intervention window to the pre-disease stage or the early stage of metabolic abnormalities is an important strategy for promoting healthy aging and reducing the burden of chronic diseases. With a focus on the characteristics of metabolic inflammation in older adults, multidimensional evaluation approaches were systematically summarized, including conventional inflammatory markers, novel biomarkers, omics technologies, dietary inflammatory indices, and imaging techniques. Particular emphasis was placed on the mechanisms by which early nutritional interventions regulate inflammatory and metabolic homeostasis through modulation of digestion and absorption, food-gut microbiota interactions, cellular biochemical reactions, inflammatory signaling pathways, and cellular and tissue constituents. The regulatory effects and human evidence of typical dietary components, including dietary carbohydrates, dietary proteins and amino acids, dietary lipids, and dietary phytochemicals, were also summarized. On this basis, the translational pathways of functional ingredients for age-friendly foods were analyzed from the perspectives of functional ingredient screening, stabilization and delivery, age-adapted application, and evaluation. Future directions involving multidimensional digital-intelligent screening and evaluation, green processing and digital manufacturing, and coordinated optimization of nutritional function and sensory properties were further discussed, providing a theoretical basis and research reference for early nutritional interventions targeting metabolic inflammation in older adults and for the development and application of functional ingredients in age-friendly foods.

Keywords： older adults; metabolic inflammation; early nutritional interventions; age-friendly foods; functional ingredients

doi：10.12301/spxb202600426

文章编号：2095-6002(2026)04-0020-17

引用格式：陆柏益,刘轩卓,王章铁. 老年代谢性炎症的早期营养干预与适老食品功能配料研究进展[J]. 食品科学技术学报,2026,44(4):20-36.

Lu Baiyi, Liu Xuanzhuo, Wang Zhangtie. Early nutritional interventions for metabolic inflammation in older adults and development of functional ingredients for age-friendly foods [J]. Journal of Food Science and Technology, 2026,44(4):20-36.

收稿日期： 2026-05-28

基金项目： 浙江省尖兵科技计划项目(2025C01100)。

Foundation： “Pioneer” and “Leading Goose” R&D Programs of Zhejiang Province (2025C01100).

第一作者： 陆柏益,男,教授,博士,主要从事食品营养与人类健康方面的研究。E-mail: bylu@zju.edu.cn。

中图分类号： TS201.4

文献标志码： A

(责任编辑：张逸群)