Synergistic Natural Products in Anti-Ageing: Mechanistic Insights, Experimental Evidence, and Translational Perspectives

Abstract

Ageing is characterised by a progressive decline in physiological function driven by oxidative stress, chronic inflammation, and metabolic imbalance. Natural products contain diverse bioactive compounds capable of regulating these interconnected processes through convergent molecular pathways. This review synthesises current evidence across six major classes of natural bioactives, including polyphenols, terpenoids, polyamines, polysaccharides, fatty acids, and bioactive peptides, and examines their roles within metabolic, redox, inflammatory, and epigenetic networks. Individually, these compounds enhance mitochondrial function, modulate AMP-activated protein kinase (AMPK)-sirtuin 1 (SIRT1)-mechanistic target of rapamycin complex 1 (mTORC1) signalling, activate the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) antioxidant pathway, suppress nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation, and improve cellular stress resilience. When used in combination, they exhibit synergistic interactions that amplify antioxidant, anti-inflammatory, and metabolic benefits, resulting in measurable improvements in lifespan and healthspan. Quantitative analyses demonstrate that rationally designed combinations achieve approximately 20-35 percent greater efficacy than single agents, reflecting coordinated multi-target reinforcement rather than simple additive effects. Overall, these insights highlight the mechanistic rationale, experimental evidence, and translational potential of synergistic natural bioactives as promising strategies for promoting healthy ageing and mitigating age-related decline.

Keywords

Natural bioactives / Anti-ageing mechanisms / AMPK-SIRT1-mTORC1 signalling / Nrf2-ARE pathway / NF-κB regulation / Synergistic combinations / Lifespan and health-span

Statement of the Use of Generative AI and AI-Assisted Technologies in the Writing Process

AI tool was used in polishing the first draft, and then the manuscript was edited by senior authors.

Author Contributions

Conceptualization, Y.S. and J.L. (Jun Lu); Methodology/Literature search, Y.S., L.S., J.H., J.L. (Johnson Liu) and Y.F.; Literature Analysis, Y.S. and L.S.; Resources, L.S., J.L. (Johnson Liu), Y.F. and J.L. (Jun Lu); Writing—Original Draft Preparation, Y.S.; Writing—Review & Editing, Y.S., L.S., J.H., J.L. (Johnson Liu), Y.F. and J.L. (Jun Lu); Supervision, J.L. (Jun Lu).

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Funding

This research received no external funding.

Declaration of Competing Interest

Authors Yuanze Sun and Lihong Sun were employed by Fuquan Biotechnology Company Ltd. The authors declare that this company was not involved in the preparation, writing, and submission of this manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

[1] World Health Organization. Ageing and Health. Ageing and Health. 2024. Available online: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health (accessed on 15 November 2025).

[2] Gilbert SF. Developmental Biology, 6th ed.; Sinauer Associates: Sunderland, MA, USA, 2000; 749p.

[3] Gems D. What is an anti-aging treatment? Exp. Gerontol. 2014, 58, 14-18. DOI:10.1016/j.exger.2014.07.003

[4] Ok SC. Insights into the Anti-Aging Prevention and Diagnostic Medicine and Healthcare. Diagnostics 2022, 12, 819. DOI:10.3390/diagnostics12040819

[5] Babich O, Ivanova S, Bakhtiyarova A, Kalashnikova O, Sukhikh S. Medicinal plants are the basis of natural cosmetics. Process Biochem. 2025, 154, 35-51. DOI:10.1016/j.procbio.2025.04.009

[6] Bhattacharya T, Dey PS, Akter R, Kabir MT, Rahman MH, Rauf A. Effect of natural leaf extracts as phytomedicine in curing geriatrics. Exp. Gerontol. 2021, 150, 111352. DOI:10.1016/j.exger.2021.111352

[7] Bjørklund G, Shanaida M, Lysiuk R, Butnariu M, Peana M, Sarac I, et al. Natural Compounds and Products from an Anti-Aging Perspective. Molecules 2022, 27, 7084. DOI:10.3390/molecules27207084

[8] Cătană CS, Atanasov AG, Berindan-Neagoe I. Natural products with anti-aging potential: Affected targets and molecular mechanisms. Biotechnol. Adv. 2018, 36, 1649-1656. DOI:10.1016/j.biotechadv.2018.03.012

[9] Görünmek M, Ballık B, Çakmak ZE, Çakmak T. Mycosporine-like amino acids in microalgae and cyanobacteria: Biosynthesis, diversity, and applications in biotechnology. Algal Res. 2024, 80, 103507. DOI:10.1016/j.algal.2024.103507

[10] Pilz M, Cavelius P, Qoura F, Awad D, Brück T. Lipopeptides development in cosmetics and pharmaceutical applications: A comprehensive review. Biotechnol. Adv. 2023, 67, 108210. DOI:10.1016/j.biotechadv.2023.108210

[11] Vaishnav P, Demain AL. Unexpected applications of secondary metabolites. Biotechnol. Adv. 2011, 29, 223-229. DOI:10.1016/j.biotechadv.2010.11.006

[12] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The Hallmarks of Aging. Cell 2013, 153, 1194-1217. DOI:10.1016/j.cell.2013.05.039

[13] Lumen Learning. Medicine LibreTexts. Biology of Aging. 2025. Available online: https://med.libretexts.org/Bookshelves/Gerontology/Biology_of_Aging_(Lumen)/zz%3A_Back_Matter/30%3A_Detailed_Licensing (accessed on 15 November 2025).

[14] Obradovic D. Five-factor theory of aging and death due to aging. Arch. Gerontol. Geriatr. 2025, 129, 105665. DOI:10.1016/j.archger.2024.105665

[15] Jin K. Modern Biological Theories of Aging. Aging Dis. 2010, 1, 72-74. PMCID: PMC2995895.

[16] Trubitsyn AG. The Mechanism of Programmed Aging: The Way to Create a Real Remedy for Senescence. Curr. Aging Sci. 2020, 13, 31-41. DOI:10.2174/1874609812666191014111422

[17] Sefanacci RG. MSD MANUAL. Overview of Aging. 2025. Available online: https://www.msdmanuals.com/home/older-people-s-health-issues/the-aging-body/overview-of-aging (accessed on 15 November 2025).

[18] Shokolenko IN. Aging: A mitochondrial DNA perspective, critical analysis and an update. World J. Exp. Med. 2014, 4, 46. DOI:10.5493/wjem.v4.i4.46

[19] Diggs J. The Cross-Linkage Theory of Aging. In Encyclopedia of Aging and Public Health; Loue SJ, Sajatovic M, Eds.; Springer: Boston, MA, USA, 2008; pp. 250-252. Availableonline:http://link.springer.com/10.1007/978-0-387-33754-8_112 (accessed on 15 November 2025).

[20] Li H, Qi Y, Jasper H. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan. Cell Host Microbe 2016, 19, 240-253. DOI:10.1016/j.chom.2016.01.008

[21] Li YR, Trush M. Defining ROS in Biology and Medicine. React. Oxyg. Species 2016, 1, 9. DOI:10.20455/ros.2016.803

[22] Sohal RS. The Rate of Living Theory:A Contemporary Interpretation. In Insect Aging; Collatz KG, Sohal RS, Eds.; Springer: Berlin/Heidelberg, Germany, 1986; pp. 23-44. Availableonline:http://link.springer.com/10.1007/978-3-642-70853-4_3 (accessed on 15 November 2025).

[23] Tohyama S, Fujita J, Hishiki T, Matsuura T, Hattori F, Ohno R, et al. Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells. Cell Metab. 2016, 23, 663-674. DOI:10.1016/j.cmet.2016.03.001

[24] Anton B, Vitetta L, Cortizo F, Sali A. Can we delay aging? The biology and science of aging. Ann. New York Acad. Sci. 2006, 1057, 525-535. DOI:10.1196/annals.1356.040

[25] Da Costa JP, Vitorino R, Silva GM, Vogel C, Duarte AC, Rocha-Santos T. A synopsis on aging—Theories, mechanisms and future prospects. Ageing Res. Rev. 2016, 29, 90-112. DOI:10.1016/j.arr.2016.06.005

[26] Rosen RS, Yarmush ML. Current Trends in Anti-Aging Strategies. Annu. Rev. Biomed. Eng. 2023, 25, 363-385. DOI:10.1146/annurev-bioeng-120122-123054

[27] Li Y, Tian X, Luo J, Bao T, Wang S, Wu X. Molecular mechanisms of aging and anti-aging strategies. Cell Commun. Signal. 2024, 22, 285. DOI:10.1186/s12964-024-01663-1

[28] Fan WY, Fan XX, Xie YJ, Yan XD, Tao MX, Zhao SL, et al. Research progress on the anti-aging effects and mechanisms of polysaccharides from Chinese herbal medicine. Food Med. Homol. 2025, 3, 9420108. DOI:10.26599/FMH.2026.9420108

[29] Li J, Wang J, Zhang N, Li Y, Cai Z, Li G, et al. Anti-aging activity and their mechanisms of natural food-derived peptides: Current advancements. Food Innov. Adv. 2023, 2, 272-290. DOI:10.48130/FIA-2023-0028

[30] Teng H, Xiao H, Li X, Huang J, Zhang B, Zeng M. Recent advances in the anti-aging effects of natural polysaccharides: Sources, structural characterization, action mechanisms and structure-activity relationships. Trends Food Sci. Technol. 2025, 160, 105000. DOI:10.1016/j.tifs.2025.105000

[31] Xiong R, Zhou X, Tang Y, Wu J, Sun Y, Teng J, et al. Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aβ(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice. Phytother. Res. 2020, 35, 954-973. DOI:10.1002/ptr.6849

[32] Zhong R, Shen L, Fan Y, Luo Q, Hong R, Sun X, et al. Anti-aging mechanism and effect of treatment with raw and wine-steamed Polygonatum sibiricum on D-galactose-induced aging in mice by inhibiting oxidative stress and modulating gut microbiota. Front. Pharmacol. 2024, 15, 1335786. DOI:10.3389/fphar.2024.1335786

[33] Shen C, Jiang J, Yang L, Wang D, Zhu W. Anti-ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: Pharmacological mechanisms and implications for drug discovery. Br. J. Pharmacol. 2016, 174, 1395-1425. DOI:10.1111/bph.13631

[34] Zhou S, Gu J, Liu R, Wei S, Wang Q, Shen H, et al. Spermine Alleviates Acute Liver Injury by Inhibiting Liver-Resident Macrophage Pro-Inflammatory Response Through ATG5-Dependent Autophagy. Front. Immunol. 2018, 9, 948. DOI:10.3389/fimmu.2018.00948

[35] Zhu W, Xiao F, Tang Y, Zou W, Li X, Zhang P, et al. Spermidine prevents high glucose-induced senescence in HT-22 cells by upregulation of CB1 receptor. Clin. Exp. Pharmacol. Physio. 2018, 45, 832-840. DOI:10.1111/1440-1681.12955

[36] Feng J, Liu S, Ma S, Zhao J, Zhang W, Qi W, et al. Protective effects of resveratrol on postmenopausal osteoporosis: Regulation of SIRT1-NF-κB signaling pathway. Acta Biochim. Et. Biophys. Sin. 2014, 46, 1024-1033. DOI:10.1093/abbs/gmu103

[37] Luo J, Si H, Jia Z, Liu D. Dietary Anti-Aging Polyphenols and Potential Mechanisms. Antioxidants 2021, 10, 283. DOI:10.3390/antiox10020283

[38] Suzuki T, Ohishi T, Tanabe H, Miyoshi N, Nakamura Y. Anti-Inflammatory Effects of Dietary Polyphenols through Inhibitory Activity against Metalloproteinases. Molecules 2023, 28, 5426. DOI:10.3390/molecules28145426

[39] Ji J, Yan H, Ye Y, Huang Z, Wang Y, Sun J, et al. Plant polysaccharides with anti-aging effects and mechanism in evaluation model Caenorhabditis elegans. Int. J. Biol. Macromol. 2025, 308, 142268. DOI:10.1016/j.ijbiomac.2025.142268

[40] Pandey KB, Rizvi SI. Plant Polyphenols as Dietary Antioxidants in Human Health and Disease. Oxidative Med. Cell. Longev. 2009, 2, 270-278. DOI:10.4161/oxim.2.5.9498

[41] Rushworth SA, Ogborne RM, Charalambos CA, O’Connell MA. Role of protein kinase C δ in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem. Biophys. Res. Commun. 2006, 341, 1007-1016. DOI:10.1016/j.bbrc.2006.01.065

[42] Xing Q, Fei W, Xu R, Fei J. Fundamental Organic Chemistry, 3rd ed.; Higher Education Press: Beijing, China, 2005.

[43] Lakey-Beitia J, Burillo AM, La Penna G, Hegde ML, Rao KS, Rao KSJ, et al. Polyphenols as Potential Metal Chelation Compounds Against Alzheimer’s Disease. J. Alzheimer’s Dis. 2021, 82, S335-S357. DOI:10.3233/JAD-200185

[44] Mu S, Yang W, Huang G. Antioxidant activities and mechanisms of polysaccharides. Chem. Biol. Drug Des. 2020, 97, 628-632. DOI:10.1111/cbdd.13798

[45] Govindharaj D, Nachimuthu S, Gonsalves DF, Kothandan R, Dhurai B, Rajamani L, et al. Molecular Docking Analysis of Chlorogenic Acid Against Matrix Metalloproteinases (MMPs). Biointerface Res. Appl. Chem. 2020, 10, 6865-6873. DOI:10.33263/BRIAC106.68656873

[46] Sánchez-Fidalgo S, Cárdeno A, Sánchez-Hidalgo M, Aparicio-Soto M, De La Lastra CA. Dietary extra virgin olive oil polyphenols supplementation modulates DSS-induced chronic colitis in mice. J. Nutr. Biochem. 2013, 24, 1401-1413. DOI:10.1016/j.jnutbio.2012.11.008

[47] Park JJ, Lee WY. Anti-glycation effect of Ecklonia cava polysaccharides extracted by combined ultrasound and enzyme-assisted extraction. Int. J. Biol. Macromol. 2021, 180, 684-691. DOI:10.1016/j.ijbiomac.2021.03.118

[48] Proshkina E, Plyusnin S, Babak T, Lashmanova E, Maganova F, Koval L, et al. Terpenoids as Potential Geroprotectors. Antioxidants 2020, 9, 529. DOI:10.3390/antiox9060529

[49] Shen Y, Zhao H, Wang X, Wu S, Wang Y, Wang C, et al. Unraveling the web of defense: the crucial role of polysaccharides in immunity. Front. Immunol. 2024, 15, 1406213. DOI:10.3389/fimmu.2024.1406213

[50] Gong L, Hou J, Yang H, Zhang X, Zhao J, Wang L, et al. Kuntai capsule attenuates premature ovarian insufficiency by activating the FOXO3/SIRT5 signaling pathway in mice: A comprehensive study using UHPLC-LTQ-Orbitrap and integrated pharmacology. J. Ethnopharmacol. 2024, 322, 117625. DOI:10.1016/j.jep.2023.117625

[51] Li R, Yi Q, Wang J, Miao Y, Chen Q, Xu Y, et al. Paeonol promotes longevity and fitness in Caenorhabditis elegans through activating the DAF-16/FOXO and SKN-1/Nrf2 transcription factors. Biomed. Pharmacother. 2024, 173, 116368. DOI:10.1016/j.biopha.2024.116368

[52] De Carvalho C, Caramujo M. The Various Roles of Fatty Acids. Molecules 2018, 23, 2583. DOI:10.3390/molecules23102583

[53] Schönfeld P, Wojtczak L. Short- and medium-chain fatty acids in energy metabolism: The cellular perspective. J. Lipid Res. 2016, 57, 943-954. DOI:10.1194/jlr.R067629

[54] Tvrzicka E, Kremmyda LS, Stankova B, Zak A. FATTY ACIDS AS BIOCOMPOUNDS: THEIR ROLE IN HUMAN METABOLISM, HEALTH AND DISEASE—A REVIEW. PART 1: CLASSIFICATION, DIETARY SOURCES AND BIOLOGICAL FUNCTIONS. Biomed. Pap. 2011, 155, 117-130. DOI:10.5507/bp.2011.038

[55] Hussey B, Lindley MR, Mastana SS. Omega 3 fatty acids, inflammation and DNA methylation: An overview. CliniCal Lipidol. 2017, 2, 24-32. DOI:10.1080/17584299.2017.1319454

[56] Moradi S, Alivand M, KhajeBishak Y, AsghariJafarabadi M, Alipour M, Chilibeck PD, et al. The effect of omega3 fatty acid supplementation on PPARγ and UCP2 expressions, resting energy expenditure, and appetite in athletes. BMC Sports Sci. Med. Rehabil. 2021, 13, 48. DOI:10.1186/s13102-021-00266-4

[57] Xie SH, Li H, Jiang JJ, Quan Y, Zhang HY. Multi-Omics Interpretation of Anti-Aging Mechanisms for ω-3 Fatty Acids. Genes 2021, 12, 1691. DOI:10.3390/genes12111691

[58] Álvarez-Mercado AI, Plaza-Diaz J. Dietary Polysaccharides as Modulators of the Gut Microbiota Ecosystem: An Update on Their Impact on Health. Nutrients 2022, 14, 4116. DOI:10.3390/nu14194116

[59] Parkar SG, Trower TM, Stevenson DE. Fecal microbial metabolism of polyphenols and its effects on human gut microbiota. Anaerobe 2013, 23, 12-19. DOI:10.1016/j.anaerobe.2013.07.009

[60] Rana A, Samtiya M, Dhewa T, Mishra V, Aluko RE. Health benefits of polyphenols: A concise review. J. Food Biochem. 2022, 46, e14264. DOI:10.1111/jfbc.14264

[61] Rudrapal M, Khairnar SJ, Khan J, Dukhyil AB, Ansari MA, Alomary MN, et al. Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action. Front. Pharmacol. 2022, 13, 806470. DOI:10.3389/fphar.2022.806470

[62] Auguste S, Yan B, Guo M. Induction of mitophagy by green tea extracts and tea polyphenols: A potential anti-aging mechanism of tea. Food Biosci. 2023, 55, 102983. DOI:10.1016/j.fbio.2023.102983

[63] Chandran AK, Stach M, Kucharska AZ, Sokół-Łętowska A, Szumny A, Moreira H, et al. Comparison of polyphenol and volatile compounds and in vitro antioxidant, anti-inflammatory, antidiabetic, anti-ageing, and anticancer activities of dry tea leaves. LWT 2025, 222, 117632. DOI:10.1016/j.lwt.2025.117632

[64] Liang H, Qu M, Ang S, Li D, He C. Anti-aging effect of tea and its phytochemicals. Food Res. Int. 2025, 214, 116572. DOI:10.1016/j.foodres.2025.116572

[65] Zhang G, Jiang W, Hu Q, Luo J, Peng X. Characterization and Anti-Aging Potency of Phenolic Compounds in Xianhu Tea Extracts. Foods 2025, 14, 737. DOI:10.3390/foods14050737

[66] Cogoi L, Marrassini C, Saint Martin EM, Alonso MR, Filip R, Anesini C. Inhibition of Glycation End Products Formation and Antioxidant Activities of Ilex paraguariensis: comparative study of fruit and leaves extracts. J. Pharmacopunct. 2023, 26, 338-347. DOI:10.3831/KPI.2023.26.4.338

[67] Gao W, Zhao C, Shang X, Li B, Guo J, Wang J, et al. Ameliorative Effects of Raisin Polyphenol Extract on Oxidative Stress and Aging In Vitro and In Vivo via Regulation of Sirt1-Nrf 2 Signaling Pathway. Foods 2024, 14, 71. DOI:10.3390/foods14010071

[68] Hu M, Cheng N, Liu R, Shao L, Yang R, Du S, et al. Red Ginseng Aqueous Extract Superior to White Ginseng Exhibited Anti-Aging Property Through IIS Signaling Pathway in Caenorhabditis elegans. Chem. Biodivers. 2025, 22, e202500604. DOI:10.1002/cbdv.202500604

[69] Wu M, Cai J, Fang Z, Li S, Huang Z, Tang Z, et al. The Composition and Anti-Aging Activities of Polyphenol Extract from Phyllanthus emblica L. Fruit. Nutr. 2022, 14, 857. DOI:10.3390/nu14040857

[70] Hao M, Ding C, Peng X, Chen H, Dong L, Zhang Y, et al. Ginseng under forest exerts stronger anti-aging effects compared to garden ginseng probably via regulating PI3K/AKT/mTOR pathway, SIRT1/NF-κB pathway and intestinal flora. Phytomedicine 2022, 105, 154365. DOI:10.1016/j.phymed.2022.154365

[71] Zefzoufi M, Fdil R, Bouamama H, Gadhi C, Katakura Y, Mouzdahir A, et al. Effect of extracts and isolated compounds derived from Retama monosperma (L.) Boiss. on anti-aging gene expression in human keratinocytes and antioxidant activity. J. Ethnopharmacol. 2021, 280, 114451. DOI:10.1016/j.jep.2021.114451

[72] Li S, He Y, Zhong S, Li Y, Di Y, Wang Q, et al. Antioxidant and Anti-Aging Properties of Polyphenol-Polysaccharide Complex Extract from Hizikia fusiforme. Foods 2023, 12, 3725. DOI:10.3390/foods12203725

[73] Yin J, Liu X, Peng F, Wang Q, Xiao Y, Liu S. Metabolite profiling, antioxidant and anti-aging activities of Siraitia grosvenorii pomace processed by solid-state fermentation with Eurotium cristatum. Process Biochem. 2023, 133, 109-120. DOI:10.1016/j.procbio.2023.08.016

[74] Bucciantini M, Leri M, Scuto M, Ontario M, Trovato Salinaro A, Calabrese EJ, et al. Xenohormesis underlyes the anti-aging and healthy properties of olive polyphenols. Mech. Ageing Dev. 2022, 202, 111620. DOI:10.1016/j.mad.2022.111620

[75] Imb M, Véghelyi Z, Maurer M, Kühnel H. Exploring Senolytic and Senomorphic Properties of Medicinal Plants for Anti-Aging Therapies. Int. J. Mol. Sci. 2024, 25, 10419. DOI:10.3390/ijms251910419

[76] Qin Y, Chen F, Tang Z, Ren H, Wang Q, Shen N, et al. Ligusticum chuanxiong Hort as a medicinal and edible plant foods: Antioxidant, anti-aging and neuroprotective properties in Caenorhabditis elegans. Front. Pharmacol. 2022, 13, 1049890. DOI:10.3389/fphar.2022.1049890

[77] Xu Y, Song J, Huang Q, Wei X, Deng Z, Song Z, et al. Functional foods and nutraceuticals with anti-aging effects: Focus on modifying the enteral microbiome. J. Funct. Foods 2025, 128, 106786. DOI:10.1016/j.jff.2025.106786

[78] Bragais EKB, Medina PMB. Effects of starter cultures on the metabolite profile, antioxidant activities, and anti-aging properties of tapuy lees. Discov. Food 2025, 5, 17. DOI:10.1007/s44187-025-00285-x

[79] Pusev MS, Klein OI, Gessler NN, Bachurina GP, Filippovich SY, Isakova EP, et al. Effect of Dihydroquercetin During Long-Last Growth of Yarrowia lipolytica Yeast: Anti-Aging Potential and Hormetic Properties. Int. J. Mol. Sci. 2024, 25, 12574. DOI:10.3390/ijms252312574

[80] Carvalho MJ, Pedrosa SS, Mendes A, Azevedo-Silva J, Fernandes J, Pintado M, et al. Anti-Aging Potential of a Novel Ingredient Derived from Sugarcane Straw Extract (SSE). Int. J. Mol. Sci. 2023, 25, 21. DOI:10.3390/ijms25010021

[81] Coutinho TE, Martins-Gomes C, Machado-Carvalho L, Nunes FM, Silva AM. Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from Cucurbita ficifolia Bouché Fruit Pulp and Peel Extracts. Molecules 2025, 30, 557. DOI:10.3390/molecules30030557

[82] Peng B, Hao Y, Chen Y, Yu S, Qu L. Chemical constituents and bioactivities of fermented rose (from Yunnan) extract. Nat. Prod. Res. 2025, 39, 6145-6152. DOI:10.1080/14786419.2024.2371995

[83] Auguste S, Yan B, Magina R, Xue L, Neto C, Guo M. Cranberry extracts and cranberry polyphenols induce mitophagy in human fibroblast cells. Food Biosci. 2024, 57, 103549. DOI:10.1016/j.fbio.2023.103549

[84] Tang Z, Zhao Z, Chen S, Lin W, Wang Q, Shen N, et al. Dragon fruit-kiwi fermented beverage: In vitro digestion, untargeted metabolome analysis and anti-aging activity in Caenorhabditis elegans. Front. Nutr. 2023, 9, 1052818. DOI:10.3389/fnut.2022.1052818

[85] Thilakarathna GC, Navaratne SB, Wickramasinghe I, Ranasinghe P, Samarkoon SR, Samarasekera JKRR. The effect of Salacia reticulata, Syzygium cumini, Artocarpus heterophyllus, and Cassia auriculata on controlling the rapid formation of advanced glycation end-products. J. Ayurveda Integr. Med. 2021, 12, 261-268. DOI:10.1016/j.jaim.2020.10.010

[86] Brinkmann V, Romeo M, Larigot L, Hemmers A, Tschage L, Kleinjohann J, et al. Aryl Hydrocarbon Receptor-Dependent and -Independent Pathways Mediate Curcumin Anti-Aging Effects. Antioxidants 2022, 11, 613. DOI:10.3390/antiox11040613

[87] Chen T, Luo S, Wang X, Zhou Y, Dai Y, Zhou L, et al. Polyphenols from Blumea laciniata Extended the Lifespan and Enhanced Resistance to Stress in Caenorhabditis elegans via the Insulin Signaling Pathway. Antioxidants 2021, 10, 1744. DOI:10.3390/antiox10111744

[88] Zhang S, Duangjan C, Tencomnao T, Wu L, Wink M, Lin J. Oolonghomobisflavans exert neuroprotective activities in cultured neuronal cells and anti-aging effects in Caenorhabditis elegans. Front. Aging Neurosci. 2022, 14, 967316. DOI:10.3389/fnagi.2022.967316

[89] Li M, Xu X, Jia Y, Yuan Y, Na G, Zhu L, et al. Transformation of mulberry polyphenols by Lactobacillus plantarum SC-5: Increasing phenolic acids and enhancement of anti-aging effect. Food Res. Int. 2024, 192, 114778. DOI:10.1016/j.foodres.2024.114778

[90] Hemagirri M, Chen Y, Gopinath SCB, Adnan M, Patel M, Sasidharan S. RNA-sequencing exploration on SIR2 and SOD genes in Polyalthia longifolia leaf methanolic extracts (PLME) mediated anti-aging effects in Saccharomyces cerevisiae BY611 yeast cells. Biogerontology 2024, 25, 705-737. DOI:10.1007/s10522-024-10104-y

[91] Abdelfattah MAO, Dmirieh M, Ben Bakrim W, Mouhtady O, Ghareeb MA, Wink M, et al. Antioxidant and anti-aging effects of Warburgia salutaris bark aqueous extract: Evidences from in silico, in vitro and in vivo studies. J. Ethnopharmacol. 2022, 292, 115187. DOI:10.1016/j.jep.2022.115187

[92] Peng X, Hao M, Zhao Y, Cai Y, Chen X, Chen H, et al. Red ginseng has stronger anti-aging effects compared to ginseng possibly due to its regulation of oxidative stress and the gut microbiota. Phytomedicine 2021, 93, 153772. DOI:10.1016/j.phymed.2021.153772

[93] Al-Harrasi A, Ali L, Ceniviva E, Al-Rawahi A, Hussain J, Hussain H, et al. Antiglycation and Antioxidant Activities and HPTLC Analysis of Boswellia sacra Oleogum Resin: The Sacred Frankincense. Trop. J. Pharm. Res. 2013, 12, 597-602. DOI:10.4314/tjpr.v12i4.23

[94] Feng Q, Li G, Xia W, Dai G, Zhou J, Xu Y, et al. The anti-aging effects of Renshen Guben on thyrotoxicosis mice: Improving immunosenescence, hypoproteinemia, lipotoxicity, and intestinal flora. Front. Immunol. 2022, 13, 983501. DOI:10.3389/fimmu.2022.983501

[95] Matacchione G, Borgonetti V, Ramini D, Silvestrini A, Ojetti M, Galeotti N, et al. Zingiber officinale Roscoe Rhizome Extract Exerts Senomorphic and Anti-Inflammatory Activities on Human Endothelial Cells. Biology 2023, 12, 438. DOI:10.3390/biology12030438

[96] Wichayapreechar P, Charoenjittichai R, Prasansuklab A, Vinardell MP, Rungseevijitprapa W. Exploring the In Vitro Antioxidant, Anti-Aging, and Cytotoxic Properties of Kaempferia galanga Linn. Rhizome Extracts for Cosmeceutical Formulations. Cosmetics 2024, 11, 97. DOI:10.3390/cosmetics11030097

[97] Saad AR, Mohyeldin MM, Takla SS, Metwally AM, Ibrahim RS. Unlocking the secrets of green and roasted coffee species: identifying anti-aging compounds through UPLC-MS/MS profiling and multivariate analysis. Microchem. J. 2025, 217, 114923. DOI:10.1016/j.microc.2025.114923

[98] Kudryavtseva A, Krasnov G, Lipatova A, Alekseev B, Maganova F, Shaposhnikov M, et al. Effects of Abies sibirica terpenes on cancer- and aging-associated pathways in human cells. Oncotarget 2016, 7, 83744-83754. DOI:10.18632/oncotarget.13467

[99] Meng J, Cheng M, Liu L, Sun J, Condori-Apfata JA, Zhao D, et al. In-vitro antioxidant and in-vivo anti-aging with stress resistance on Caenorhabditis elegans of herbaceous peony stamen tea. Int. J. Food Prop. 2021, 24, 1349-1366. DOI:10.1080/10942912.2021.1967385

[100] Stavropoulou MI, Stathopoulou K, Cheilari A, Benaki D, Gardikis K, Chinou I, et al. NMR metabolic profiling of Greek propolis samples: Comparative evaluation of their phytochemical compositions and investigation of their anti-ageing and antioxidant properties. J. Pharm. Biomed. Anal. 2021, 194, 113814. DOI:10.1016/j.jpba.2020.113814

[101] Elgamal AM, Ahmed RF, Abd-ElGawad AM, El Gendy AENG, Elshamy AI, Nassar MI. Chemical Profiles, Anticancer, and Anti-Aging Activities of Essential Oils of Pluchea dioscoridis (L.) DC. and Erigeron bonariensis L. Plants 2021, 10, 667. DOI:10.3390/plants10040667

[102] Prommaban A, Kheawfu K, Chittasupho C, Sirilun S, Hemsuwimon K, Chaiyana W. Phytochemical, Antioxidant, Antihyaluronidase, Antityrosinase, and Antimicrobial Properties of Nicotiana tabacum L. Leaf Extracts. Evid.-Based Complement. Altern. Med. 2022, 2022, 5761764. DOI:10.1155/2022/5761764

[103] Teratani T, Kasahara N, Ijichi T, Fujimoto Y, Sakuma Y, Sata N, et al. Activation of whole body by high levels of polyamine intake in rats. Amino Acids 2021, 53, 1695-1703. DOI:10.1007/s00726-021-03079-4

[104] Xu TT, Li H, Dai Z, Lau GK, Li BY, Zhu WL, et al. Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice. Aging 2020, 12, 6401-6414. DOI:10.18632/aging.103035

[105] Du ZQ, Xie JB, Ji SY, Zhou W, Tao ZS. Spermidine prevents iron overload-induced impaired bone mass by activating SIRT1/SOD2 signaling in senile rat model. Redox Rep. 2025, 30, 2485666. DOI:10.1080/13510002.2025.2485666

[106] Yang J, Zhang CR, Li ZX, Gao YH, Jiang L, Zhang J, et al. Spermine alleviates myocardial cell aging by inhibiting mitochondrial oxidative stress damage. Eur. J. Pharmacol. 2025, 997, 177477. DOI:10.1016/j.ejphar.2025.177477

[107] Kim G, Kim M, Kim M, Park C, Yoon Y, Lim DH, et al. Spermidine-induced recovery of human dermal structure and barrier function by skin microbiome. Commun. Biol. 2021, 4, 231. DOI:10.1038/s42003-020-01619-4

[108] Liu Y, Hu W, Pei X, Zhu J, Meng H, Lyu Y, et al. Polydeoxyribonucleotide-spermidine nanoparticles: Preparation, characterization, and verification of skin anti-aging efficacy. Int. J. Biol. Macromol. 2025, 322, 146984. DOI:10.1016/j.ijbiomac.2025.146984

[109] Ueno D, Ikeda K, Yamazaki E, Katayama A, Urata R, Matoba S. Spermidine improves angiogenic capacity of senescent endothelial cells, and enhances ischemia-induced neovascularization in aged mice. Sci. Rep. 2023, 13, 8338. DOI:10.1038/s41598-023-35447-3

[110] Guan B, Li C, Yang Y, Lu Y, Sun Y, Su L, et al. Effect of spermidine on radiation-induced long-term bone marrow cell injury. Int. Immunopharmacol. 2023, 114, 109557. DOI:10.1016/j.intimp.2022.109557

[111] Jeong JW, Cha HJ, Han MH, Hwang SJ, Lee DS, Yoo JS, et al. Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish. Biomol. Ther. 2018, 26, 146-156. DOI:10.4062/biomolther.2016.272

[112] Kojić D, Spremo J, Đorđievski S, Čelić T, Vukašinović E, Pihler I, et al. Spermidine supplementation in honey bees: Autophagy and epigenetic modifications. PLoS ONE 2024, 19, e0306430. DOI:10.1371/journal.pone.0306430

[113] Rossmann C, Darko A, Kager G, Ledinski G, Wonisch W, Wagner T, et al. Natural Polyamine Spermidine Inhibits the In Vitro Oxidation of LDL. Molecules 2025, 30, 955. DOI:10.3390/molecules30040955

[114] Uemura T, Matsunaga M, Yokota Y, Takao K, Furuchi T. Inhibition of Polyamine Catabolism Reduces Cellular Senescence. Int. J. Mol. Sci. 2023, 24, 13397. DOI:10.3390/ijms241713397

[115] Baek AR, Hong J, Song KS, Jang AS, Kim DJ, Chin SS, et al. Spermidine attenuates bleomycin-induced lung fibrosis by inducing autophagy and inhibiting endoplasmic reticulum stress (ERS)-induced cell death in mice. Exp. Mol. Med. 2020, 52, 2034-2045. DOI:10.1038/s12276-020-00545-z

[116] Jiang D, Guo Y, Niu C, Long S, Jiang Y, Wang Z, et al. Exploration of the Antioxidant Effect of Spermidine on the Ovary and Screening and Identification of Differentially Expressed Proteins. Int. J. Mol. Sci. 2023, 24, 5793. DOI:10.3390/ijms24065793

[117] Wei C, Wang Y, Li M, Li H, Lu X, Shao H, et al. Spermine inhibits Endoplasmic Reticulum Stress—Induced Apoptosis: A New Strategy to Prevent Cardiomyocyte Apoptosis. Cell Physiol. Biochem. 2016, 38, 531-544. DOI:10.1159/000438648

[118] Bai J, Zhang Y, Li N, Cui Z, Zhang H, Liu Y, et al. Supplementation of spermidine enhances the quality of postovulatory aged porcine oocytes. Cell Commun. Signal. 2024, 22, 499. DOI:10.1186/s12964-024-01881-7

[119] Wirth A, Wolf B, Huang CK, Glage S, Hofer SJ, Bankstahl M, et al. Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length. GeroScience 2021, 43, 673-690. DOI:10.1007/s11357-020-00310-0

[120] Qiang Y, Min Y, Li W, Chen D, Zhang S, Chen H, et al. Mitigating natural aging in Drosophila melanogaster with Tremella fuciformis polysaccharides. Food Biosci. 2025, 71, 107145. DOI:10.1016/j.fbio.2025.107145

[121] Finazzi M, Bovio F, Forcella M, Lasagni M, Fusi P, Di Gennaro P. Beneficial Effects of In Vitro Reconstructed Human Gut Microbiota by Ginseng Extract Fermentation on Intestinal Cell Lines. Microorganisms 2025, 13, 192. DOI:10.3390/microorganisms13010192

[122] Fang Z, Li Y, Chen H, Lian C, Zhang X, Wang J, et al. Crude polysaccharides of Helvella leucopus induces myogenic differentiation of C2C 12 cells and raises levels of genes involved in mitochondrial dynamics. J. Funct. Foods 2024, 119, 106291. DOI:10.1016/j.jff.2024.106291

[123] Duan H, Li J, Fan L. Agaricus bisporus Polysaccharides Ameliorates Behavioural Deficits in D-Galactose-Induced Aging Mice: Mediated by Gut Microbiota. Foods 2023, 12, 424. DOI:10.3390/foods12020424

[124] Saad S, Abd-Alla H, Aly H, Shalaby N, Afify AEM, Helal H, et al. Citharexylum Spinosum: LC-ESI-TOF-MS Analysis and Anti-Aging Evolution on D-Galactose-Induced Aging through Anti-Inflammatory, Antioxidant Activity and Regulation of the Gut Microbiota in Rats. Egypt. J. Chem. 2024, 67, 527-544. DOI:10.21608/ejchem.2024.277822.9483

[125] Wei Y, Jiang Y, Liu M, Zhang X, Guo S, Su S, et al. Chemical structures of Lycii fructus polysaccharides tailored the gut microbiota composition of aged Caenorhabditis elegans. Food Hydrocoll. 2025, 169, 111608. DOI:10.1016/j.foodhyd.2025.111608

[126] Fang Z, Liu N, Fan Z, Wang W, Luo J, Qiu Y, et al. Cistanche deserticola polysaccharides—Companilactobacillus crustorum LBK 1001 complex relieves aging in Caenorhabditis elegans. Food Biosci. 2025, 68, 106486. DOI:10.1016/j.fbio.2025.106486

[127] Feng ST, You CT, Pan ZK, Gao WY, Wang DD, Hu LL. The anti-aging effects of Chlorella polysaccharide extract in Caenorhabditis elegans. Nat. Prod. Res. 2025, 39, 6390-6395. DOI:10.1080/14786419.2024.2371562

[128] Feng A, Zhao Z, Liu C, Du C, Gao P, Liu X, et al. Study on characterization of Bupleurum chinense polysaccharides with antioxidant mechanisms focus on ROS relative signaling pathways and anti-aging evaluation in vivo model. Int. J. Biol. Macromol. 2024, 266, 131171. DOI:10.1016/j.ijbiomac.2024.131171

[129] Yan X, Miao J, Zhang B, Liu H, Ma H, Sun Y, et al. Study on semi-bionic extraction of Astragalus polysaccharide and its anti-aging activity in vivo. Front. Nutr. 2023, 10, 1201919. DOI:10.3389/fnut.2023.1201919

[130] Hu Y, Zhou J, Cao Y, Zhang J, Zou L. Anti-aging effects of polysaccharides from quinoa (Chenopodium quinoa Willd.) in improving memory and cognitive function. J. Funct. Foods 2022, 94, 105097. DOI:10.1016/j.jff.2022.105097

[131] Huang Y, He M, Zhang J, Cheng S, Cheng X, Chen H, et al. White Tea Aqueous Extract: A Potential Anti-Aging Agent Against High-Fat Diet-Induced Senescence in Drosophila melanogaster. Foods 2024, 13, 4034. DOI:10.3390/foods13244034

[132] Liang L, Yue Y, Zhong L, Liang Y, Shi R, Luo R, et al. Anti-aging activities of Rehmannia glutinosa Libosch. crude polysaccharide in Caenorhabditis elegans based on gut microbiota and metabonomic analysis. Int. J. Biol. Macromol. 2023, 253, 127647. DOI:10.1016/j.ijbiomac.2023.127647

[133] Luo D, Liu X, Guan J, Jang G, Hua Y, Zhang X, et al. Effects of Tremella fuciformis-Derived Polysaccharides with Different Molecular Weight on D-Galactose-Induced Aging of Mice. Pol. J. Food Nutr. Sci. 2023, 73, 163-174. DOI:10.31883/pjfns/163612

[134] Chen Y, Ouyang Y, Chen X, Chen R, Ruan Q, Farag MA, et al. Hypoglycaemic and anti-ageing activities of green alga Ulva lactuca polysaccharide via gut microbiota in ageing-associated diabetic mice. Int. J. Biol. Macromol. 2022, 212, 97-110. DOI:10.1016/j.ijbiomac.2022.05.109

[135] Yang JJ, Zhang X, Dai JF, Ma YG, Jiang JG. Effect of fermentation modification on the physicochemical characteristics and anti-aging related activities of Polygonatum kingianum polysaccharides. Int. J. Biol. Macromol. 2023, 235, 123661. DOI:10.1016/j.ijbiomac.2023.123661

[136] Bai X, Wang M, Xu T, Zhou S, Chu W. Antioxidant and anti-aging activities of Acanthopanax senticosus polysaccharide CQ-1 in nematode Caenorhabditis elegans. Int. J. Biol. Macromol. 2025, 297, 139925. DOI:10.1016/j.ijbiomac.2025.139925

[137] Okoro NO, Odiba AS, Yu Q, He B, Liao G, Jin C, et al. Polysaccharides Extracted from Dendrobium officinale Grown in Different Environments Elicit Varying Health Benefits in Caenorhabditis elegans. Nutrients 2023, 15, 2641. DOI:10.3390/nu15122641

[138] Yue Y, Liang L, Zhang H, Li C, Zhao M, Yang M, et al. Antioxidant and anti-aging effects of purified Rehmannia glutinosa polysaccharide in Caenorhabditis elegans. Process Biochem. 2024, 137, 41-53. DOI:10.1016/j.procbio.2023.12.009

[139] Zhang C, Song X, Cui W, Yang Q. Antioxidant and anti-ageing effects of enzymatic polysaccharide from Pleurotus eryngii residue. Int. J. Biol. Macromol. 2021, 173, 341-350. DOI:10.1016/j.ijbiomac.2021.01.030

[140] Cheng Y, He S, Wei Z, Meng Y, Su D, Li X, et al. Structural characterizations and anti-aging activities of a homogeneous polysaccharide derived from Coix seed-lactic acid bacteria fermentation. Int. J. Biol. Macromol. 2025, 330, 147879. DOI:10.1016/j.ijbiomac.2025.147879

[141] Wen J, Liu J, Nie Y, Wang P, Shao Y, Zhang Y, et al. A novel yolk-shell nanoparticles delivery system based on Polygonatum polysaccharides and PCC1 for synergistic anti-aging. Food Res. Int. 2025, 220, 117188. DOI:10.1016/j.foodres.2025.117188

[142] Wu L, Liu X, Hu R, Chen Y, Xiao M, Liu B, et al. Prebiotic Agrocybe cylindracea crude polysaccharides combined with Lactobacillus rhamnosus GG postpone aging-related oxidative stress in mice. Food Funct. 2022, 13, 1218-1231. DOI:10.1039/D1FO02079J

[143] Guo X, Xin Q, Wei P, Hua Y, Zhang Y, Su Z, et al. Antioxidant and anti-aging activities of Longan crude and purified polysaccharide (LP-A) in nematode Caenorhabditis elegans. Int. J. Biol. Macromol. 2024, 267, 131634. DOI:10.1016/j.ijbiomac.2024.131634

[144] Zhang X, Liu Y, Zhang X, Liu H, Wang B, Li C, et al. Structural characterization and anti-ageing activity of polysaccharide from Exocarpium Citrulli. J. Mol. Struct. 2024, 1316, 139073. DOI:10.1016/j.molstruc.2024.139073

[145] Hou M, Li X, Li X, Zhang J, Jia L. Structure Analysis, Antioxidant Activity, Anti-Aging, and Organ Protective Effects of Pholiota adiposa Residue Polysaccharides. Starch-Stärke 2023, 75, 2200237. DOI:10.1002/star.202200237

[146] Zhang X, Liu L, Luo J, Peng X. Anti-aging potency correlates with metabolites from in vitro fermentation of edible fungal polysaccharides using human fecal intestinal microflora. Food Funct. 2022, 13, 11592-11603. DOI:10.1039/D2FO01951E

[147] Li Y, Zhao X, Wang J, Yu Q, Ren J, Jiang Z, et al. Characterization and anti-aging activities of polysaccharide from Rana dybowskii Guenther. Front. Pharmacol. 2024, 15, 1370631. DOI:10.3389/fphar.2024.1370631

[148] Wang W, Li S, Zhu Y, Zhu R, Du X, Cui X, et al. Effect of Different Edible Trichosanthes Germplasm on Its Seed Oil to Enhance Antioxidant and Anti-Aging Activity in Caenorhabditis elegans. Foods 2024, 13, 503. DOI:10.3390/foods13030503

[149] Mora I, Pérez-Santamaria A, Tortajada-Pérez J, Vázquez-Manrique RP, Arola L, Puiggròs F. Structured Docosahexaenoic Acid (DHA) Enhances Motility and Promotes the Antioxidant Capacity of Aged C. elegans. Cells 2023, 12, 1932. DOI:10.3390/cells12151932

[150] Huangfu J, Liu J, Peng C, Suen YL, Wang M, Jiang Y, et al. DHA-rich marine microalga Schizochytrium mangrovei possesses anti-ageing effects on Drosophila melanogaster. J. Funct. Foods. 2013, 5, 888-896. DOI:10.1016/j.jff.2013.01.038

[151] Ramirez-Tortosa CL, Varela-López A, Navarro-Hortal MD, Ramos-Pleguezuelos FM, Márquez-Lobo B, Ramirez-Tortosa Mc, et al. Longevity and Cause of Death in Male Wistar Rats Fed Lifelong Diets Based on Virgin Olive Oil, Sunflower Oil, or Fish Oil. J. Gerontol. Ser. A 2020, 75, 442-451. DOI:10.1093/gerona/glz091

[152] Chen J, Wu S, Wu Y, Zhuang P, Zhang Y, Jiao J. Long-term dietary DHA intervention prevents telomere attrition and lipid disturbance in telomerase-deficient male mice. Eur. J. Nutr. 2023, 62, 1867-1878. DOI:10.1007/s00394-023-03120-0

[153] Wu D, Jia Y, Liu Y, Shang M. Dose-response relationship of dietary Omega-3 fatty acids on slowing phenotypic age acceleration: A cross-sectional study. Front. Nutr. 2024, 11, 1424156. DOI:10.3389/fnut.2024.1424156

[154] González-Hedström D, Amor S, De La Fuente-Fernández M, Tejera-Muñoz A, Priego T, Martín AI, et al. A Mixture of Algae and Extra Virgin Olive Oils Attenuates the Cardiometabolic Alterations Associated with Aging in Male Wistar Rats. Antioxidants 2020, 9, 483. DOI:10.3390/antiox9060483

[155] Lu H, Li L, Zou Z, Han B, Gong M. The Therapeutic Potential of Hemp Seed Oil in D-Galactose-Induced Aging Rat Model Was Determined through the Combined Assessment of 1H NMR Metabolomics and 16S rRNA Gene Sequencing. Metabolites 2024, 14, 304. DOI:10.3390/metabo14060304

[156] Prommaban A, Kuanchoom R, Seepuan N, Chaiyana W. Evaluation of Fatty Acid Compositions, Antioxidant, and Pharmacological Activities of Pumpkin (Cucurbita moschata) Seed Oil from Aqueous Enzymatic Extraction. Plants 2021, 10, 1582. DOI:10.3390/plants10081582

[157] Vu DC, Vu QT, Huynh L, Lin CH, Alvarez S, Vo XT, et al. Evaluation of fatty acids, phenolics and bioactivities of spent coffee grounds prepared from Vietnamese coffee. Int. J. Food Prop. 2021, 24, 1548-1558. DOI:10.1080/10942912.2021.1977657

[158] Lee JH, Seo EY, Lee YM. Comparative investigation on variations of nutritional components in whole seeds and seed coats of Korean black soybeans for different crop years and screening of their antioxidant and anti-aging properties. Food Chem. X 2023, 17, 100572. DOI:10.1016/j.fochx.2023.100572

[159] Shi H, Hu X, Zheng H, Li C, Sun L, Guo Z, et al. Two novel antioxidant peptides derived from Arca subcrenata against oxidative stress and extend lifespan in Caenorhabditis elegans. J. Funct. Foods 2021, 81, 104462. DOI:10.1016/j.jff.2021.104462

[160] Ye X, Yang R, Riaz T, Chen J. Stability and antioxidant function of Porphyra haitanensis proteins during simulated gastrointestinal digestion: Effects on stress resistance and lifespan extension in Caenorhabditis elegans. Int. J. Biol. Macromol. 2025, 293, 139291. DOI:10.1016/j.ijbiomac.2024.139291

[161] He W, Xie J, Xia Z, Chen X, Xiao J, Cao Y, et al. A novel peptide derived from Haematococcus pluvialis residue exhibits anti-aging activity in Caenorhabditis elegans via the insulin/IGF-1 signaling pathway. Food Funct. 2023, 14, 5576-5588. DOI:10.1039/D3FO00383C

[162] Liu J, Zhao Y, Leng F, Xiao X, Jiang W, Guo S. A Hydrolyzed Soybean Protein Enhances Oxidative Stress Resistance in C. elegans and Modulates Gut-Immune Axis in BALB/c Mice. Antioxidants 2025, 14, 689. DOI:10.3390/antiox14060689

[163] Amakye WK, Hou C, Xie L, Lin X, Gou N, Yuan E, et al. Bioactive anti-aging agents and the identification of new anti-oxidant soybean peptides. Food Biosci. 2021, 42, 101194. DOI:10.1016/j.fbio.2021.101194

[164] Sakhenberg E, Linkova N, Kraskovskaya N, Krieger D, Polyakova V, Medvedev D, et al. The Influence of Short Peptides on Cell Senescence and Neuronal Differentiation. Curr. Issues Mol. Biol. 2025, 47, 739. DOI:10.3390/cimb47090739

[165] Alnadari F, Wang R, Cheng G, Nasiru M, Baldi S, Almogahed M, et al. Development Characterization and Anti-Aging Potential of Fish Collagen Peptide-Based Beverages with Bovine Colostrum. Iran. J. Chem. Chem. Eng. 2025, 44, 1161-1176. DOI:10.30492/ijcce.2025.2037572.6729

[166] Cardeira M, Bernardo A, Leonardo IC, Gaspar FB, Marques M, Melgosa R, et al. Cosmeceutical Potential of Extracts Derived from Fishery Industry Residues: Sardine Wastes and Codfish Frames. Antioxidants 2022, 11, 1925. DOI:10.3390/antiox11101925

[167] Guo HX, Wang BB, Wu HY, Feng HY, Zhang HY, Gao W, et al. Turtle peptide and its derivative peptide ameliorated DSS-induced ulcerative colitis by inhibiting inflammation and modulating the composition of the gut microbiota. Int. Immunopharmacol. 2024, 132, 112024. DOI:10.1016/j.intimp.2024.112024

[168] Gensous N, Garagnani P, Santoro A, Giuliani C, Ostan R, Fabbri C, et al. One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: A pilot study from the NU-AGE project. GeroScience 2020, 42, 687-701. DOI:10.1007/s11357-019-00149-0

[169] Hou JY, Xu H, Cao GZ, Tian LL, Wang LH, Zhu NQ, et al. Multi-omics reveals Dengzhan Shengmai formulation ameliorates cognitive impairments in D-galactose-induced aging mouse model by regulating CXCL12/CXCR4 and gut microbiota. Front. Pharmacol. 2023, 14, 1175970. DOI:10.3389/fphar.2023.1175970

[170] Rinott E, Meir AY, Tsaban G, Zelicha H, Kaplan A, Knights D, et al. The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: A randomized controlled trial. Genome Med. 2022, 14, 29. DOI:10.1186/s13073-022-01015-z

[171] Yaskolka Meir A, Rinott E, Tsaban G, Zelicha H, Kaplan A, Rosen P, et al. Effect of green-Mediterranean diet on intrahepatic fat: The DIRECT PLUS randomised controlled trial. Gut 2021, 70, 2085-2095. DOI:10.1136/gutjnl-2020-323106

[172] Hoffmann A, Meir AY, Hagemann T, Czechowski P, Müller L, Engelmann B, et al. A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: The DIRECT PLUS randomized controlled trial. Metabolism 2023, 145, 155594. DOI:10.1016/j.metabol.2023.155594

[173] Zhang SJ, Xu TT, Li L, Xu YM, Qu ZL, Wang XC, et al. Bushen-Yizhi formula ameliorates cognitive dysfunction through SIRT1/ER stress pathway in SAMP8 mice. Oncotarget 2017, 8, 49338-49350. DOI:10.18632/oncotarget.17638

[174] Chen W, Liu S, Xu G, Liu X, Shi Y, Wang G, et al. Zuogui and Yougui pills extend lifespan and improve ageing biomarkers via kaempferol-mediated mitophagy in Caenorhabditis elegans. Biogerontology 2025, 26, 172. DOI:10.1007/s10522-025-10317-9

[175] Meng F, Li J, Rao Y, Wang W, Fu Y. Gengnianchun Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1 Signalling Pathway. Oxidative Med. Cell. Longev. 2018, 2018, 4740739. DOI:10.1155/2018/4740739

[176] Hou L, Jiang M, Guo Q, Shi W. Zymolytic Grain Extract (ZGE) Significantly Extends the Lifespan and Enhances the Environmental Stress Resistance of Caenorhabditis elegans. Int. J. Mol. Sci. 2019, 20, 3489. DOI:10.3390/ijms20143489

[177] Wan F, Zhi D, Liu D, Xian J, Li M, AbuLizi A, et al. Lifespan extension in Caenorhabiditis elegans by several traditional Chinese medicine formulas. Biogerontology 2014, 15, 377-387. DOI:10.1007/s10522-014-9508-1

[178] Nurkolis F, Purnomo AF, Alisaputra D, Gunawan WB, Qhabibi FR, Park W, et al. In silico and in vitro studies reveal a synergistic potential source of novel anti-ageing from two Indonesian green algae. J. Funct. Foods 2023, 104, 105555. DOI:10.1016/j.jff.2023.105555

[179] Chen W, Wang J, Shi J, Yang X, Yang P, Wang N, et al. Longevity Effect of Liuwei Dihuang in Both Caenorhabditis elegans and Aged Mice. Aging Dis. 2019, 10, 578. DOI:10.14336/AD.2018.0604

[180] Zeng L, Yang Z, Yun T, Fan S, Pei Z, Chen Z, et al. Antiaging effect of a Jianpi-yangwei formula in Caenorhabditis elegans. BMC Complement. Altern. Med. 2019, 19, 313. DOI:10.1186/s12906-019-2704-4

[181] Jensen JB, Dollerup OL, Møller AB, Billeskov TB, Dalbram E, Chubanava S, et al. A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals. JCI Insight 2022, 7, e158314. DOI:10.1172/jci.insight.158314

[182] Omori M. Anti-Ageing Medicine as Edible Health Insurance: Self-Care and Ageing Well among Older Adults Living in Australia and Japan. Ph.D. Dissertation, Swinburne University of Technology, Melbourne, Australia, 2015.

[183] Boonpisuttinant K, Unkeaw S, Chomphoo W, Udompong S, Khong HY. In Vitro Anti-ageing Activities of the Extracts of Low-Grade Pineapple and Lime Key from Sob Prab Cooperative Limited, Lampang, Thailand. J. Smart Sci. Technol. 2022, 2, 46-59. DOI:10.24191/jsst.v2i1.24

[184] Su S, Chen G, Gao M, Zhong G, Zhang Z, Wei D, et al. Kai-Xin-San protects against mitochondrial dysfunction in Alzheimer’s disease through SIRT3/NLRP3 pathway. Chin. Med. 2023, 18, 26. DOI:10.1186/s13020-023-00722-y

[185] Xing C, Zeng Z, Shan Y, Guo W, Shah R, Wang L, et al. A Network Pharmacology-based Study on the Anti-aging Properties of Traditional Chinese Medicine Sisheng Bulao Elixir. Comb. Chem. High. Throughput Screen. 2024, 27, 1840-1849. DOI:10.2174/0113862073276253231114063813

[186] Sun W, Shahrajabian MH, Cheng Q. Therapeutic Roles of Goji Berry and Ginseng in Traditional Chinese. J. Nutr. Food Secur. 2019, 4, 4293-4305. DOI:10.18502/jnfs.v4i4.1727

[187] Akbarian M, Khani A, Eghbalpour S, Uversky VN. Bioactive Peptides: Synthesis, Sources, Applications, and Proposed Mechanisms of Action. Int. J. Mol. Sci. 2022, 23, 1445. DOI:10.3390/ijms23031445

[188] Izadi M, Sadri N, Abdi A, Zadeh MMR, Jalaei D, Ghazimoradi MM, et al. Anti-ageing natural supplements: The main players in promoting healthy lifespan. Nutr. Res. Rev. 2024, 38, 522-539. DOI:10.1017/S0954422424000301

[189] La Manna S, Di Natale C, Florio D, Marasco D. Peptides as Therapeutic Agents for Inflammatory-Related Diseases. Int. J. Mol. Sci. 2018, 19, 2714. DOI:10.3390/ijms19092714

[190] Bahrami SA, Bakhtiari N. Ursolic acid regulates aging process through enhancing of metabolic sensor proteins level. Biomed. Pharmacother. 2016, 82, 8-14. DOI:10.1016/j.biopha.2016.04.047

[191] Nie H, Wang Y, Qin Y, Gong X. Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo. Cell Biol. Int. 2016, 40, 770-778. DOI:10.1002/cbin.10612

[192] Song L, Zhang S. Anti-Aging Activity and Modes of Action of Compounds from Natural Food Sources. Biomolecules 2023, 13, 1600. DOI:10.3390/biom13111600

[193] Lin X, Liu W, Hu X, Liu Z, Wang F, Wang J. The role of polyphenols in modulating mitophagy: Implications for therapeutic interventions. Pharmacol. Res. 2024, 207, 107324. DOI:10.1016/j.phrs.2024.107324

[194] Safer AM, Afzal M, Nomani M, Mousa SA. Green Tea Extract in the Management of Hepatic Fibrosis. In Tea in Health and Disease Prevention; Academic Press: Cambridge, MA, USA, 2013; pp. 903-909. DOI:10.1016/B978-0-12-384937-3.00076-8

[195] Zhang H, Wang M, Xiao J. Stability of polyphenols in food processing. In Advances in Food and Nutrition Research; Academic Press: Cambridge, MA, USA, 2022; pp. 1-45. Availableonline:https://linkinghub.elsevier.com/retrieve/pii/S1043452622000158 (accessed on 15 November 2025).

[196] Andrés CMC, Pérez De La Lastra JM, Juan CA, Plou FJ, Pérez-Lebeña E. Polyphenols as Antioxidant/Pro-Oxidant Compounds and Donors of Reducing Species: Relationship with Human Antioxidant Metabolism. Processes 2023, 11, 2771. DOI:10.3390/pr11092771

[197] Wu J, Hsieh TC, Lu X, Wang Z. Induction of Quinone Reductase NQO1 by Resveratrol in Human K562 Cells Involves the Antioxidant Response Element ARE and is Accompanied by Nuclear Translocation of Transcription Factor Nrf2. Med. Chem. 2006, 2, 275-285. DOI:10.2174/157340606776930709

[198] Milenkovic D, Jude B, Morand C. miRNA as molecular target of polyphenols underlying their biological effects. Free Radic. Biol. Med. 2013, 64, 40-51. DOI:10.1016/j.freeradbiomed.2013.05.046

[199] Quan Y, Park W, Jin J, Kim W, Park SK, Kang KP. Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κB-TGF-β1/Smad Signaling Pathway. Int. J. Mol. Sci. 2020, 21, 402. DOI:10.3390/ijms21020402

[200] Guan Y, Li L, Yang R, Lu Y, Tang J. Targeting mitochondria with natural polyphenols for treating Neurodegenerative Diseases: A comprehensive scoping review from oxidative stress perspective. J. Transl. Med. 2025, 23, 572. DOI:10.1186/s12967-025-06605-0

[201] Mthembu SXH, Dludla PV, Ziqubu K, Nyambuya TM, Kappo AP, Madoroba E, et al. The Potential Role of Polyphenols in Modulating Mitochondrial Bioenergetics within the Skeletal Muscle: A Systematic Review of Preclinical Models. Molecules 2021, 26, 2791. DOI:10.3390/molecules26092791

[202] Stankovic S, Mutavdzin Krneta S, Djuric D, Milosevic V, Milenkovic D. Plant Polyphenols as Heart’s Best Friends: From Health Properties, to Cellular Effects, to Molecular Mechanisms of Action. Int. J. Mol. Sci. 2025, 26, 915. DOI:10.3390/ijms26030915

[203] Wu M, Luo Q, Nie R, Yang X, Tang Z, Chen H. Potential implications of polyphenols on aging considering oxidative stress, inflammation, autophagy, and gut microbiota. Crit. Rev. Food Sci. Nutr. 2020, 61, 2175-2193. DOI:10.1080/10408398.2020.1773390

[204] Feng G, Han K, Yang Q, Feng W, Guo J, Wang J, et al. Interaction of Pyrogallol-Containing Polyphenols with Mucin Reinforces Intestinal Mucus Barrier Properties. J. Agric. Food Chem. 2022, 70, 9536-9546. DOI:10.1021/acs.jafc.2c03564

[205] Han P, Yu Y, Zhang L, Ruan Z. Citrus peel ameliorates mucus barrier damage in HFD-fed mice. J. Nutr. Biochem. 2023, 112, 109206. DOI:10.1016/j.jnutbio.2022.109206

[206] Graßmann J. Terpenoids as Plant Antioxidants. Vitam. Horm. 2005, 72, 505-535. DOI:10.1016/S0083-6729(05)72015-X

[207] Masyita A, Mustika Sari R, Dwi Astuti A, Yasir B, Rahma Rumata N, Emran TB, et al. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chem. X 2022, 13, 100217. DOI:10.1016/j.fochx.2022.100217

[208] Rajasekar J, Perumal MK, Vallikannan B. A critical review on anti-angiogenic property of phytochemicals. J. Nutr. Biochem. 2019, 71, 1-15. DOI:10.1016/j.jnutbio.2019.04.006

[209] Everett SA, Dennis MF, Patel KB, Maddix S, Kundu SC, Willson RL. Scavenging of Nitrogen Dioxide, Thiyl, and Sulfonyl Free Radicals by the Nutritional Antioxidant ²-Carotene. J. Biol. Chem. 1996, 271, 3988-3994. DOI:10.1074/jbc.271.8.3988

[210] Okoro NO, Odiba AS, Osadebe PO, Omeje EO, Liao G, Fang W, et al. Bioactive Phytochemicals with Anti-Aging and Lifespan Extending Potentials in Caenorhabditis elegans. Molecules 2021, 26, 7323. DOI:10.3390/molecules26237323

[211] Chen L, Yao H, Chen X, Wang Z, Xiang Y, Xia J, et al. Ginsenoside Rg1 Decreases Oxidative Stress and Down-Regulates Akt/mTOR Signalling to Attenuate Cognitive Impairment in Mice and Senescence of Neural Stem Cells Induced by d-Galactose. Neurochem. Res. 2017, 43, 430-440. DOI:10.1007/s11064-017-2438-y

[212] Park YM, Park SN. Inhibitory Effect of Lupeol on MMPs Expression using Aged Fibroblast through Repeated UVA Irradiation. Photochem. Photobiol. 2018, 95, 587-594. DOI:10.1111/php.13022

[213] Hwang YP, Jeong HG. The coffee diterpene kahweol induces heme oxygenase-1 via the PI3K and p38/Nrf2 pathway to protect human dopaminergic neurons from 6-hydroxydopamine-derived oxidative stress. FEBS Lett. 2008, 582, 2655-2662. DOI:10.1016/j.febslet.2008.06.045

[214] Wang Q, Zhao X, Jiang Y, Jin B, Wang L. Functions of Representative Terpenoids and Their Biosynthesis Mechanisms in Medicinal Plants. Biomolecules 2023, 13, 1725. DOI:10.3390/biom13121725

[215] Lenis YY, Elmetwally MA, Maldonado-Estrada JG, Bazer FW. Physiological importance of polyamines. Zygote 2017, 25, 244-255. DOI:10.1017/S0967199417000120

[216] Sagar NA, Tarafdar S, Agarwal S, Tarafdar A, Sharma S. Polyamines: Functions, Metabolism, and Role in Human Disease Management. Med. Sci. 2021, 9, 44. DOI:10.3390/medsci9020044

[217] Michael AJ. Polyamines in Eukaryotes, Bacteria, and Archaea. J. Biol. Chem. 2016, 291, 14896-14903. DOI:10.1074/jbc.R116.734780

[218] Sarvananda L, Madhuranga D, Palihaderu PADS, Sri Lanka B. Health Effects of Polyamines: An Overview of Polyamines as a Health-Promoting Agent for Human Health. Biochem. Anal. Biochem. 2023, 12, 503. DOI:10.35248/2161-1009.23.12.503

[219] Tofalo R, Cocchi S, Suzzi G. Polyamines and Gut Microbiota. Front. Nutr. 2019, 6, 16. DOI:10.3389/fnut.2019.00016

[220] Xuan M, Gu X, Li J, Huang D, Xue C, He Y. Polyamines: Their significance for maintaining health and contributing to diseases. Cell Commun. Signal. 2023, 21, 348. DOI:10.1186/s12964-023-01373-0

[221] Arthur R, Jamwal S, Kumar P. A review on polyamines as promising next-generation neuroprotective and anti-aging therapy. Eur. J. Pharmacol. 2024, 978, 176804. DOI:10.1016/j.ejphar.2024.176804

[222] Toro-Funes N, Bosch-Fusté J, Veciana-Nogués MT, Izquierdo-Pulido M, Vidal-Carou MC. In vitro antioxidant activity of dietary polyamines. Food Res. Int. 2013, 51, 141-147. DOI:10.1016/j.foodres.2012.11.036

[223] Soda K. Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation. Cells 2022, 11, 164. DOI:10.3390/cells11010164

[224] Løvaas E. Antioxidative effects of polyamines. J. Am. Oil Chem. Soc. 1991, 68, 353-358. DOI:10.1007/BF02663749

[225] Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, et al. Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 2009, 11, 1305-1314. DOI:10.1038/ncb1975

[226] Ni YQ, Liu YS. New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases. Aging Dis. 2021, 12, 1948. DOI:10.14336/AD.2021.0603

[227] Pignatti C, Tantini B, Stefanelli C, Flamigni F. Signal transduction pathways linking polyamines to apoptosis. Amino Acids 2004, 27, 359-365. DOI:10.1007/s00726-004-0115-3

[228] Seiler N, Raul F. Polyamines and apoptosis. J. Cell. Mol. Med. 2005, 9, 623-642. DOI:10.1111/j.1582-4934.2005.tb00493.x

[229] Choi Y, Park H. Anti-inflammatory effects of spermidine in lipopolysaccharide-stimulated BV2 microglial cells. J. Biomed. Sci. 2012, 19, 31. DOI:10.1186/1423-0127-19-31

[230] Hussain T, Tan B, Ren W, Rahu N, Dad R, Kalhoro DH, et al. Polyamines: Therapeutic perspectives in oxidative stress and inflammatory diseases. Amino Acids 2017, 49, 1457-1468. DOI:10.1007/s00726-017-2447-9

[231] Soda K. Biological Effects of Polyamines on the Prevention of Aging-associated Diseases and on Lifespan Extension. Food Sci. Technol. Res. 2015, 21, 145-157. DOI:10.3136/fstr.21.145

[232] Zhang C, Zhen Y, Weng Y, Lin J, Xu X, Ma J, et al. Research progress on the microbial metabolism and transport of polyamines and their roles in animal gut homeostasis. J. Anim. Sci. Biotechnol. 2025, 16, 57. DOI:10.1186/s40104-025-01193-x

[233] Kurihara S. Polyamine metabolism and transport in gut microbes. Biosci. Biotechnol. Biochem. 2022, 86, 957-966. DOI:10.1093/bbb/zbac080

[234] Feng YL, Cao G, Chen DQ, Vaziri ND, Chen L, Zhang J, et al. Microbiome-metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease. Cell Mol. Life Sci. 2019, 76, 4961-4978. DOI:10.1007/s00018-019-03155-9

[235] Zhao Q, Huang JF, Cheng Y, Dai MY, Zhu WF, Yang XW, et al. Polyamine metabolism links gut microbiota and testicular dysfunction. Microbiome 2021, 9, 224. DOI:10.1186/s40168-021-01157-z

[236] Devi N, Sarmah M, Khatun B, Maji TK. Encapsulation of active ingredients in polysaccharide-protein complex coacervates. Adv. Colloid. Interface Sci. 2017, 239, 136-145. DOI:10.1016/j.cis.2016.05.009

[237] Mizrahy S, Peer D. Polysaccharides as building blocks for nanotherapeutics. Chem. Soc. Rev. 2012, 41, 2623-2640. DOI:10.1039/C1CS15239D

[238] D’Ayala GG, Malinconico M, Laurienzo P. Marine Derived Polysaccharides for Biomedical Applications: Chemical Modification Approaches. Molecules 2008, 13, 2069-2106. DOI:10.3390/molecules13092069

[239] Liu Z, Jiao Y, Wang Y, Zhou C, Zhang Z. Polysaccharides-based nanoparticles as drug delivery systems. Adv. Drug Deliv. Rev. 2008, 60, 1650-1662. DOI:10.1016/j.addr.2008.09.001

[240] Ngwuluka NC. Responsive polysaccharides and polysaccharides-based nanoparticles for drug delivery. In Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications, Volume 1; Woodhead Publishing: Cambridge, UK, 2018; pp. 531-554. DOI:10.1016/B978-0-08-101997-9.00023-0

[241] Yang L, Zhang LM. Chemical structural and chain conformational characterization of some bioactive polysaccharides isolated from natural sources. Carbohydr. Polym. 2009, 76, 349-361. DOI:10.1016/j.carbpol.2008.12.015

[242] Wang XH, Cheng XD, Wang D, Wu Z, Chen Y, Wu QX. Antioxidant and anti-aging effects of polysaccharide LDP-1 from wild Lactarius deliciosus on Caenorhabditis elegans. Food Nutr. Res. 2022, 66, 8110. DOI:10.29219/fnr.v66.8110

[243] Guo X, Luo J, Qi J, Zhao X, An P, Luo Y, et al. The Role and Mechanism of Polysaccharides in Anti-Aging. Nutrients 2022, 14, 5330. DOI:10.3390/nu14245330

[244] Wu L, Huang D, Wang S, Wang J, Guo Q, Chen X. Role and mechanism of seaweed polysaccharides in regulating mitochondrial dysfunction: A review. J. Food Sci. 2025, 90, e70100. DOI:10.1111/1750-3841.70100

[245] Ma C, Yang K, Wang Y, Dai X. Anti-Aging Effect of Agar Oligosaccharide on Male Drosophila melanogaster and Its Preliminary Mechanism. Mar. Drugs 2019, 17, 632. DOI:10.3390/md17110632

[246] Yin Z, Liang Z, Li C, Wang J, Ma C, Kang W. Immunomodulatory effects of polysaccharides from edible fungus: A review. Food Sci. Hum. Wellness 2021, 10, 393-400. DOI:10.1016/j.fshw.2021.04.001

[247] Zhang D, Liu J, Cheng H, Wang H, Tan Y, Feng W, et al. Interactions between polysaccharides and gut microbiota: A metabolomic and microbial review. Food Res. Int. 2022, 160, 111653. DOI:10.1016/j.foodres.2022.111653

[248] Lin J, Yu J, Wang X, Shi R, Liang Y, Li J, et al. Research progress on the anti-aging effect of polysaccharides of traditional Chinese medicine: Using Caenorhabditis elegans as an animal model. FASEB J. 2025, 39, e70454. DOI:10.1096/fj.202403250RR

[249] Yu G, Zhang Q, Wang Y, Yang Q, Yu H, Li H, et al. Sulfated polysaccharides from red seaweed Gelidium amansii: Structural characteristics, anti-oxidant and anti-glycation properties, and development of bioactive films. Food Hydrocoll. 2021, 119, 106820. DOI:10.1016/j.foodhyd.2021.106820

[250] Li C, Dong S, Zeng A, Phyo SH, Li L, Zhao W. Structural analysis and anti-glycation activity of a novel polysaccharide isolated from Dendrobium officinale. Food Biosci. 2025, 68, 106817. DOI:10.1016/j.fbio.2025.106817

[251] Pan LH, Feng BJ, Wang JH, Zha XQ, Luo JP. Structural Characterization and Anti-glycation Activity in vitro of a Water-soluble Polysaccharide from Dendrobium huoshanense. J. Food Biochem. 2013, 37, 313-321. DOI:10.1111/j.1745-4514.2011.00633.x

[252] Ratnayake WMN, Galli C. Fat and Fatty Acid Terminology, Methods of Analysis and Fat Digestion and Metabolism: A Background Review Paper. Ann. Nutr. Metab. 2009, 55, 8-43. DOI:10.1159/000228994

[253] Chen Y, Yang L, Wang K, An Y, Wang Y, Zheng Y, et al. Relationship between fatty acid intake and aging: A Mendelian randomization study. Aging 2024, 16, 5711-5739. DOI:10.18632/aging.205674

[254] Zhou L, Xiong JY, Chai YQ, Huang L, Tang ZY, Zhang XF, et al. Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system. Front. Psychiatry 2022, 13, 933704. DOI:10.3389/fpsyt.2022.933704

[255] Edwards IJ, O’Flaherty JT. Omega-3 Fatty Acids and PPARgamma in Cancer. PPAR Res. 2008, 2008, 358052. DOI:10.1155/2008/358052

[256] Gani OABSM. Are fish oil omega-3 long-chain fatty acids and their derivatives peroxisome proliferator-activated receptor agonists? Cardiovasc. Diabetol. 2008, 7, 6. DOI:10.1186/1475-2840-7-6

[257] Li J, Lin YCD, Zuo HL, Huang HY, Zhang T, Bai JW, et al. Dietary Omega-3 PUFAs in Metabolic Disease Research: A Decade of Omics-Enabled Insights (2014-2024). Nutrients 2025, 17, 1836. DOI:10.3390/nu17111836

[258] Zou B, Zhao D, Zhou S, Kang JX, Wang B. Insight into the effects of Omega-3 fatty acids on gut microbiota: Impact of a balanced tissue Omega-6/Omega-3 ratio. Front. Nutr. 2025, 12, 1575323. DOI:10.3389/fnut.2025.1575323

[259] Costantini L, Molinari R, Farinon B, Merendino N. Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int. J. Mol. Sci. 2017, 18, 2645. DOI:10.3390/ijms18122645

[260] Kumar V, Rohilla A, Ahire JJ. Omega-3 fatty acids and the gut microbiome: A new frontier in cardiovascular disease prevention. Discov. Med. 2025, 2, 53. DOI:10.1007/s44337-025-00212-0

[261] Bhandari D, Rafiq S, Gat Y, Gat P, Waghmare R, Kumar V. A Review on Bioactive Peptides: Physiological Functions, Bioavailability and Safety. Int. J. Pept. Res. Ther. 2019, 26, 139-150. DOI:10.1007/s10989-019-09823-5

[262] Zaky AA, Simal-Gandara J, Eun JB, Shim JH, Abd El-Aty AM. Bioactivities, Applications, Safety, and Health Benefits of Bioactive Peptides From Food and By-Products: A Review. Front. Nutr. 2022, 8, 815640. DOI:10.3389/fnut.2021.815640

[263] Nong NTP, Hsu JL. Bioactive Peptides: An Understanding from Current Screening Methodology. Processes 2022, 10, 1114. DOI:10.3390/pr10061114

[264] Yao W, Zhang Y, Zhang G. Marine peptides as potential anti-aging agents: Preparation, characterization, mechanisms of action, and future perspectives. Food Chem. 2024, 460, 140413. DOI:10.1016/j.foodchem.2024.140413

[265] Ndinguri M, Bhowmick M, Tokmina-Roszyk D, Robichaud T, Fields G. Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities. Molecules 2012, 17, 14230-14248. DOI:10.3390/molecules171214230

[266] Wang J, Wu Y, Chen Z, Chen Y, Lin Q, Liang Y. Exogenous Bioactive Peptides Have a Potential Therapeutic Role in Delaying Aging in Rodent Models. Int. J. Mol. Sci. 2022, 23, 1421. DOI:10.3390/ijms23031421

[267] Apone F, Barbulova A, Colucci MG. Plant and Microalgae Derived Peptides Are Advantageously Employed as Bioactive Compounds in Cosmetics. Front. Plant Sci. 2019, 10, 756. DOI:10.3389/fpls.2019.00756

[268] Hao ZW, Zhang ZY, Wang ZP, Wang Y, Chen JY, Chen TH, et al. Bioactive peptides and proteins for tissue repair: microenvironment modulation, rational delivery, and clinical potential. Mil. Med. Res. 2024, 11, 75. DOI:10.1186/s40779-024-00576-x

[269] Hipkiss AR, Brownson C, Carrier MJ. Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech. Ageing Dev. 2001, 122, 1431-1445. DOI:10.1016/S0047-6374(01)00272-X

[270] Qiu Z, Yan M, Li Q, Liu D, Van Den Steen PE, Wang M, et al. Definition of peptide inhibitors from a synthetic peptide library by targeting gelatinase B/matrix metalloproteinase-9 (MMP-9) and TNF-α converting enzyme (TACE/ADAM-17). J. Enzym. Inhib. Med. Chem. 2011, 27, 533-540. DOI:10.3109/14756366.2011.599323

[271] Hipkiss AR, Brownson C. A possible new role for the anti-ageing peptide carnosine. Cell. Mol. Life Sci. (CMLS) 2000, 57, 747-753. DOI:10.1007/s000180050039

[272] Jiang SJ, Tsai PI, Peng SY, Chang CC, Chung Y, Tsao HH, et al. A potential peptide derived from cytokine receptors can bind proinflammatory cytokines as a therapeutic strategy for anti-inflammation. Sci. Rep. 2019, 9, 2317. DOI:10.1038/s41598-018-36492-z

[273] Magrone T, Jirillo E. Nutraceuticals in immunosenescence. In Anti-Ageing Nutrients, 1st ed.; Neves D, Ed.; Wiley: Hoboken, NJ, USA, 2015; pp. 183-202. Available online: https://onlinelibrary.wiley.com/doi/10.1002/9781118823408.ch5 (accessed on 15 November 2025).

[274] Ding X, Ma X, Meng P, Yue J, Li L, Xu L. Potential Effects of Traditional Chinese Medicine in Anti-Aging and Aging-Related Diseases: Current Evidence and Perspectives. Clin. Interv. Aging 2024, 19, 681-693. DOI:10.2147/CIA.S447514

[275] Dhanjal DS, Bhardwaj S, Sharma R, Bhardwaj K, Kumar D, Chopra C, et al. Plant Fortification of the Diet for Anti-Ageing Effects: A Review. Nutrients 2020, 12, 3008. DOI:10.3390/nu12103008

[276] Reis Da Silva TMH. Herbal Solutions for Longevity:Anti-Ageing Compounds From Traditional Medicine. In Drug Discovery and Antiaging Approaches for Human Longevity; Chen JT, Ed.; IGI Global Scientific Publishing: Palmdale, PA, USA, 2025; pp. 325-350. Available online: https://services.igi-global.com/resolvedoi/resolve.aspx?doi=10.4018/979-8-3693-9730-5.ch009 (accessed on 15 November 2025).

[277] Naik S, Lagishetty C. Polyamines: Potential anti-inflammatory agents and their possible mechanism of action. Indian J. Pharmacol. 2008, 40, 121. DOI:10.4103/0253-7613.42305

[278] Li W, Chen H, Xu B, Wang Y, Zhang C, Cao Y, et al. Research progress on classification, sources and functions of dietary polyphenols for prevention and treatment of chronic diseases. J. Future Foods 2023, 3, 289-305. DOI:10.1016/j.jfutfo.2023.03.001