The role of fermented foods in healthy longevity: A review of potential anti-aging mechanisms

Abstract

The progressive aging of the global population has prompted considerable interest in the development of safe and effective strategies to promote healthy longevity. Diet constitutes a substantial modifiable factor, with fermented foods emerging as a pivotal domain of research. The health benefits of these foods are largely attributed to viable microorganisms and a rich array of bioactive compounds, such as organic acids, phenolics, and peptides, which are generated during fermentation. This review methodically synthesizes recent advances regarding the anti-aging potential of fermented foods, emphasizing the pivotal molecular and cellular mechanisms involved. Specifically, we elucidate major pathways, including the scavenging of reactive oxygen species, the mitigation of oxidative stress, and the regulation of critical signal transduction networks. Furthermore, this review analyzes the multifaceted benefits of fermented foods, which encompass gut microbiota modulation, immune system regulation, anti-inflammatory responses, and the enhancement of host antioxidant defense systems. By integrating current evidence, this work establishes a theoretical framework to guide the development of innovative fermented food products and strategies targeting healthy aging.

Graphical abstract

Highlights

• •Fermented foods exhibit anti-aging potential through both shared mechanisms (e.g., redox regulation and inflammation control) and product-specific effects shaped by microbial consortia and food matrices.
• •Fermentation-derived bioactive compounds, rather than nutrients alone, play a central role in modulating key aging-related pathways, including Nrf2, AMPK, sirtuin signaling, and NF-κB.
• •Gut microbiota remodeling emerges as a critical integrative node linking oxidative stress, immune regulation, and metabolic homeostasis during aging.
• •Evidence from cellular and animal models highlights mechanistic diversity across fermented dairy, soy, grains, vegetables, and teas, underscoring context-dependent rather than universal effects.
• •Translational application of fermented foods for healthy aging requires improved mechanistic resolution, standardized fermentation strategies, and rigorous clinical validation.

1. Introduction

The accelerated aging of the global population has led to a notable increase in the prevalence of health issues among the elderly (Octary et al., 2025). Projections indicate that by 2050, the proportion of the global population aged 60 and above will reach 22 %. The impact of aging and its associated diseases on individuals' health and quality of life has increased exponentially worldwide (Gao et al., 2023). This demographic shift is projected to result in a substantial escalation in healthcare expenditures (Ros and Carrascosa, 2020). Therefore, identifying safe and effective interventions to mitigate the effects of aging and extend the healthy lifespan of humans will have a profound impact on health, the economy, and society (Qin et al., 2026).

Aging is a natural phenomenon involving irreversible degenerative changes at the molecular, cellular, tissue, and organ levels (Fatt et al., 2022). These modifications enhance susceptibility to disease and represent a significant risk factor for a range of chronic illnesses, including cancer, metabolic disorders, cardiovascular disease, and neurodegenerative conditions (Barone et al., 2022; Conrad et al., 2023; Song and Zhang, 2023). In order to develop effective interventions, research has focused on the underlying mechanisms, recently summarized as twelve scientifically validated “Hallmarks of Aging” (Fig. 1). The hallmarks of aging include genomic instability, telomere attrition, epigenetic alterations, and cellular senescence. These hallmarks, when taken together, lead to integrative features such as chronic inflammation and ecological dysregulation(López-Otín et al., 2013).

Fig. 1.

The hallmarks of aging and diseases of aging(López-Otín et al., 2023).

Among the hallmarks of aging, chronic low-grade inflammation, known as inflammaging, and dysbiosis (predominantly manifesting as gut microbiota dysbiosis) have been identified as the primary drivers of unhealthy aging (Yin et al., 2025). Crucially, these two characteristics are highly plastic and can be effectively regulated through dietary and microbial interventions. Although aging is inevitable, research into decelerating the process has persisted (Jothi and Kulka, 2024). Current strategies often focus on pharmacological or dietary interventions (Partridge et al., 2020). However, the potential for negative side effects from anti-aging drugs (Juricic et al., 2022; Soukas et al., 2019) has intensified the search for safer alternatives. Researchers have increasingly focused on identifying natural anti-aging substances within functional foods (Teng et al., 2025), as diet is a fundamental regulator of human metabolism.

Within this field, traditional fermented foods (e.g., yogurt, kefir, kimchi, fermented soy products) are regarded as unique functional foods, precisely because their health benefits are fundamentally driven by microbiology (Iwatani and Yamamoto, 2019). Their potential anti-aging properties are mediated through both viable probiotic microorganisms and fermentation-derived bioactive factors (Orisakwe et al., 2020; Singh et al., 2021). These microbial factors are uniquely positioned to target the gut dysbiosis and inflammaging hallmarks identified as critical in the aging process. While several studies have reported the anti-aging effects of fermented foods (Das et al., 2020), systematic reviews focusing on the anti-aging mechanisms of fermented foods are still scarce. Although the microbial composition of fermented foods has been extensively cataloged, there is currently no comprehensive review that systematically links specific starter cultures (e.g., Lactobacillus plantarum) and their metabolic signatures directly to the molecular regulatory mechanisms of host aging.

This review synthesizes the current evidence on the anti-aging properties of fermented foods through a mechanistic lens. The present study focuses on the synergistic duality of viable microbes and fermentation products, distinguishing this from a generalized perspective. A multi-scale analysis of preclinical and clinical data has been conducted to elucidate key longevity networks, including redox regulation, immunomodulation, metabolic signaling, and gut-host interactions. The review also assesses challenges in safety and translation. The resulting framework is designed to support rational product design and precise nutritional strategies for the aging population.

2. Anti-aging effects of different fermented foods

According to the International Scientific Association for Probiotics and Prebiotics (ISAPP), fermented foods are defined as “foods made through desired microbial growth and enzymatic conversions of food components” (Marco et al., 2021). Fermented foods have been shown to contain functional molecules that have been demonstrated to be beneficial to the human body. These foods achieve the purpose of preventing disease and promoting health by regulating the physiological functions of the human body (Cui et al., 2024; Gonzalez-Gonzalez et al., 2023; Sørensen et al., 2023). There is a wide variety of fermented foods, and common fermented foods include yoghurt, kimchi, soy sauce, tempeh, bread, and a variety of alcoholic products (Zhang et al., 2023). Since Metchnikoff's suggestion (Mackowiak, 2013), that high consumption of lactobacillus-fermented milk may prolong the life expectancy of the general population, in-depth studies have been conducted on the anti-aging effects of fermented foods, and a large number of functional fermented foods with promising have been found (Das et al., 2020). Depending on the raw materials (Fig. 2), fermented foods can be divided into the following categories: fermented soybean products (e.g., bean paste, soy sauce), fermented dairy products (e.g., yogurt, cheese), fermented cereals (e.g., vinegar, yellow wine), and other fermented foods (e.g., kimchi, black tea).

Fig. 2.

Classification of fermented foods.

2.1. Fermented dairy products

Fermented dairy products, such as yogurt, cheese, kefir, and koumiss, are produced through the metabolic activity of starter cultures (e.g., Lactobacillus, Bifidobacterium, and yeasts) on milk substrates(Bintsis, 2024). Beyond extending shelf life and enhancing flavor, fermentation enzymatically breaks down lactose, proteins, and fats into bioactive metabolites, including free amino acids, short-chain fatty acids (SCFAs), and bioactive peptides, thereby enhancing nutritional bioavailability (Rizzoli and Biver, 2024).

As outlined in Table 1, a comprehensive review of both human clinical trials and preclinical studies has demonstrated the potential of fermented dairy to mitigate age-related physiological decline. In human clinical trials, probiotic-fermented dairy has demonstrated significant efficacy in combating immunosenescence. For instance, Dong et al. (2013) reported that the daily consumption of a probiotic drink containing Lactobacillus casei Shirota (1.3 × 10¹⁰ CFU) over a period of four weeks significantly enhanced Natural Killer (NK) cell activity and promoted an anti-inflammatory cytokine profile (increased IL-10/IL-12 ratio) in healthy older adults (55–74 years). In addition, observational studies have indicated that the long-term consumption of cheese is associated with enhanced cognitive processing speed in the elderly. Furthermore, interventions incorporating Lactobacillus reuteri fortified dairy have been observed to mitigate bone loss in older women (Nilsson et al., 2018). In animal models, the anti-aging mechanisms of fermented dairy have been frequently linked to the regulation of oxidative stress and the gut-brain axis. Zhang et al. (2017) demonstrated that exopolysaccharides (EPS) isolated from Tibetan kefir significantly upregulated antioxidant enzymes (SOD, GSH-Px) and reduced plasma malondialdehyde (MDA) levels in aging mice. Notably, this antioxidant effect was strongly correlated with the modulation of gut microbiota, specifically the enrichment of beneficial Blautia and Butyricicoccus genera. Furthermore, fermentation-derived peptides play a critical role in neuroprotection. Ano et al. (2018) identified novel tryptophan-tyrosine (GTWY) peptides in fermented whey that improved memory function in aged mice. Mechanistically, these peptides inhibited monoamine oxidase B (MAO-B) activity, thereby preserving hippocampal dopamine levels. Additionally, recent evidence highlights the potential of cheese extracts in longevity. Cardin et al. (2021) found that lipid extracts from raw goat milk cheese extended the lifespan of Caenorhabditis elegans by activating the DAF-16/FOXO signaling pathway, a conserved regulator of longevity.

Table 1.

Anti-aging effects of fermented dairy products.

Fermented Product	Microorganism & Fermentation Conditions	Key Bioactive Compound	Experimental Model (n/Sex/Age)	Intervention (Dose & Duration)	Key Outcomes & Mechanisms	Refer
Probiotic drink	Lactobacillus casei Shirota	Live probiotic	Healthy older adults (n = 30; 18Female/12Male; 55–74 y)	130 mL/day (1.3 × 1010 CFU) for 4 weeks	Outcomes: ↑ Innate immunity (NK cell activity); ↓ T-cell activation (CD25 MFI); Shift to anti-inflammatory profile (↑ IL-10/IL-12 ratio). Mechanism: Attenuation of immunosenescence.	Dong et al. (2013)
Naturally fermented Xinjiang yogurt	Lactobacillus plantarum KSFY02	Live probiotic	Kunming mice (n = 50; 25Female/25Male; 6 weeks)	1.0 × 109 CFU/kg BW/day for 10 weeks	Outcomes: Preserved organ indices; ↑ SOD; GSH-Px; GSH; ↓ NO; MDA. Mechanism: Activation of Nrf2–HO-1 antioxidant pathway (↑ Nrf2, SOD, CAT, HO-1, ↓ Nos2).	X. Zhao et al. (2019)
Tibetan kefir	Lactobacillus plantarum YW11 (37 °C; 18 h)	Exopolysaccharide (EPS)	ICR mice (n = 48; Male; 8 weeks)	EPS: 20–50 mg/kg/d or Fermented milk: 20 mL/kg/d for 12 weeks	Outcomes: ↑ SOD; GSH-Px; CAT; T-AOC; ↓ MDA; ↑ SCFA production. Mechanism: Microbiota modulation (↓ Flexispira, ↑ Blautia, ↑ Butyricicoccus) linked to ROS scavenging.	Zhang et al. (2017)
Tibet kefir grains	Lactobacillus plantarum MA2 (CGMCC3005; 37 °C; 18 h)	Live probiotic	Male Kunming mice (n = 60; 8 weeks)	108–1010 CFU/day (oral gavage) for 6 weeks	Outcomes: ↑ Antioxidant capacity (SOD, GSH-Px); ↓ MDA. Mechanism: Sustained stable intestinal colonization (ileum, colon, feces) supporting antioxidant effects.	Tang et al. (2016)
Fermented whey protein	Enzymatic fermentation (Aspergillus melleus or Bacillus stearothermophilus)	Trp-Tyr (GTWY) containing peptides	C57BL/6 mice (n = 24; Male; 22 months)	1–10 mg/kg for 10 days	Outcomes: Improved working and episodic memory in amnesia/aged mice. Mechanism: Inhibition of MAO-B activity leading to ↑ hippocampal dopamine levels.	Ano et al. (2018)
Dadih (Buffalo milk)	Lactic acid bacteria (Natural fermentation in bamboo)	Bioactive peptides; Live probiotics	Rattus norvegicus (n = 30; Male; 24 months)	4.5 g/day (once or twice daily) for 42 days	Outcomes: ↓ Renal oxidative damage (MDA); Attenuated renal interstitial fibrosis. Mechanism: Peptide- and probiotic-driven ROS scavenging and lipid peroxidation inhibition.	Harnavi et al. (2020)
Kumiss (Mare milk)	Natural mixed microbiota (LAB and yeasts)	Unsaturated fatty acids; Milk proteins	BALB/c mice (n = 40; Male; 20–25 g)	20 mL/kg (i.p.; weekly) for 20 weeks	Outcomes: ↓ Oxidative stress (8-OHdG; OSI; TOC); ↑ TAC; GSH. Mechanism: Upregulated SIRT2 and SIRT3 expression (hepatic/colonic) indicating sirtuin-mediated metabolic regulation.	Gulmez and Atakisi (2020)
Camembert cheese	Surface fermentation (Penicillium candidum)	Oleamide	5xFAD transgenic mice (n = 22; Female; 3 months)	2 % (w/w) fermented cheese in diet for 3 months	Outcomes: ↓ Cerebral Aβ burden; ↓ Hippocampal inflammation (TNF-α; MIP-1α); ↑ Neurotrophic support (BDNF; GDNF). Mechanism: Oleamide-mediated microglial activation toward anti-inflammatory phenotype (↑ CD36, ↓ CD68).	Ano et al. (2015)
Selenium-enriched yogurt	Limosilactobacillus fermentum CGMCC 17434 (42 °C; 6 h + post-ripening)	Organic selenium; Resveratrol	ICR mice (n = 70; Male; 18–22 g)	0.1–0.4 mL/day for 8 weeks	Outcomes: ↑ GSH, SOD; ↓ ROS, MDA, PCO; Attenuated systemic/neuroinflammation (↓ IL-1β, IL-6, TNF-α). Mechanism: Combined antioxidant-anti-inflammatory protection of spleen/hippocampus.	Luo et al. (2025)
Raw goat milk cheese	Natural fermentation (Traditional cheese-making)	Lipophilic and hydrophilic cheese extracts	C. elegans (N2 wild-type & mutants)	0.5–1 % (w/v) extracts	Outcomes: Extended lifespan; Enhanced oxidative stress resistance; ↓ ROS levels. Mechanism: DAF-16 nuclear translocation required (DAF-2/DAF-16 signaling) and p38 MAPK pathway activation.	Cardin et al. (2021)
Eight French raw-milk cheeses	Traditional diverse processing (Goat; cow; ewe)	Bioactive peptides; Phenolic compounds; S-amino acids	C. elegans N2	1 % (w/v) cheese fractions for 5 days	Outcomes: Enhanced survival and ↓ ROS accumulation under oxidative stress. Mechanism: Activation of IIS/DAF-16 and p38 MAPK/SKN-1 pathways (↑ ctl-2, sod-3).	Diet et al. (2024)
Buffalo & Cow Milk Cheddar	Traditional ripening (8 °C; up to 6 months)	Water-soluble peptides (WSPs)	Caco-2 human intestinal epithelial cells	100–300 μg/mL WSP extracts (24 h)	Outcomes: ↑ ABTS scavenging activity; ↓ Intracellular ROS in t-BHP-induced stress. Note: Higher activity observed in buffalo milk cheese (linked to WSP content).	Huma et al. (2018)
Himalayan cheese (Kalari)	L. plantarum; L. casei; L. brevis (37 °C; 24 h fermentation)	Bioactive peptides	MCF-7, HCT-116, IMR-32 cells; Mouse monocytes	10–50 mg/mL water-soluble extract	Outcomes: Dose-dependent anti-proliferative activity in cancer lines. Mechanism: Immunomodulatory effects (↑ NO production in monocytes) via proteolysis-derived peptides.	Mushtaq et al. (2019)

Abbreviations: 8-OHdG, 8-hydroxy-2′-deoxyguanosine; Aβ, amyloid beta; ABTS, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); BDNF, brain-derived neurotrophic factor; BW, body weight; CAT, catalase; CD, cluster of differentiation; CFU, colony-forming units; DAF, dauer formation; GDNF, glial cell line-derived neurotrophic factor; GSH, glutathione; GSH-Px, glutathione peroxidase; HO-1, heme oxygenase-1; i.p., intraperitoneal; IIS, insulin/IGF-1 signaling; IL, interleukin; MAPK, mitogen-activated protein kinase; MFI, mean fluorescence intensity; MIP-1α, macrophage inflammatory protein-1 alpha; Nrf2, nuclear factor erythroid 2-related factor 2; NO, nitric oxide; Nos2, nitric oxide synthase 2; OSI, oxidative stress index; PCO, protein carbonyls; ROS, reactive oxygen species; SIRT, sirtuin; SOD, superoxide dismutase; T-AOC/TAC, total antioxidant capacity; t-BHP, tert-butyl hydroperoxide; TNF-α, tumor necrosis factor alpha; TOC, total oxidant capacity; WSPs, water-soluble peptides.

2.2. Fermented soy products

Fermented soy products are foods or condiments with special flavors and shapes made from beans as the main raw material, fermented by micro-organisms and then blended (Park et al., 2019). A broad array of fermented soy products, including soy sauce, tempeh, soy paste, and fermented bean curd (see Fig. 3), have garnered significant consumer appeal worldwide, thereby becoming integral components of global diets. During fermentation, soy products undergo biochemical transformations that break down macromolecules into soluble small molecules and convert indigestible substances into absorbable nutrients (Cao et al., 2019). This process reduces anti-nutritional factors like protease inhibitors, oligosaccharides, and lectins (Miao et al., 2024), while generating beneficial compounds. These include active peptides, unsaturated fatty acids, isoflavone glycosides, γ-aminobutyric acid and various vitamins (Qiao et al., 2022).

Fig. 3.

Process flow chart of the main bean products(Liu et al., 2022).

As outlined in Table 2, emerging evidence from clinical trials and animal models underscores the multifaceted anti-aging properties of fermented soy products. In human clinical trials, fermented soy interventions have demonstrated efficacy in regulating metabolic health and oxidative stress. For instance, Lee et al. (2006) reported that acute consumption of traditional Dark Soy Sauce significantly decreased plasma lipid peroxidation biomarkers (F2-isoprostanes) in healthy adults, attributed to its potent postprandial radical scavenging activity. Furthermore, Jeong et al. (2021) conducted a 12-week intervention with Chungkookjang (a Korean fermented soybean paste) in overweight adults, observing significant reductions in visceral fat and apolipoprotein B, suggesting a potential role in mitigating age-related metabolic dysregulation. In animal models, fermented soy products have been shown to exert anti-aging effects across multiple aging-related domains, including neuroprotection, metabolic regulation, sarcopenia prevention, and lifespan extension. In terms of neuroprotection, Chan et al. (2018) demonstrated that tempeh supplementation attenuated cognitive decline and reduced brain amyloid-β accumulation in senescence-accelerated mice, an effect mechanistically associated with activation of the Nrf2 antioxidant signaling pathway. Beyond cognitive outcomes, fermented soy products have also shown efficacy in mitigating age-related metabolic deterioration. Koh et al. (2023) found that fermented black soybean produced by Bacillus subtilis var. natto prevented sarcopenia and reduced visceral fat accumulation in aged mice, effects that were closely linked to modulation of gut microbiota composition and associated metabolic pathways. At the organismal level, lifespan extension has also been observed, as Ibe et al. (2013) demonstrated that a water-soluble extract of natto significantly prolonged the lifespan of Caenorhabditis elegans and delayed the accumulation of lipofuscin, a hallmark of cellular aging, through activation of stress-response pathways.

Table 2.

Anti-aging effects of fermented soy products.

Fermented Product	Microorganism & Fermentation Conditions	Key Bioactive Compound	Experimental Model (n/Sex/Age)	Intervention (Dose & Duration)	Key Outcomes & Mechanisms	Reference
Dark soy sauce (DSS)	Traditional fermentation	Antioxidant compounds (Total phenolics)	Healthy adults (n = 24; 12Female/12Male; ∼23 y)	30 mL DSS (single dose w/meal)	Outcomes: ↓ Lipid peroxidation (Plasma F2-isoprostanes); ↓ Diastolic BP (transient). Mechanism: Rapid postprandial radical scavenging in plasma.	Lee et al. (2006)
Chungkookjang	Mixed Bacillus spp. (Salt-free; 24–72 h)	γ-PGA; Isoflavones; Peptides	Overweight/obese adults (n = 52)	Human: 26 g/d (12 weeks)	Outcomes: ↓ Visceral fat & ApoB. Mechanism: Attenuation of oxidative stress and neuroinflammation.	Jeong et al. (2021)
Novel fermented soybean food	Bacillus spp.; L. delbrueckii subsp. bulgaricus; Hansenula anomala (37 °C; 21 h)	Peptides; Phenolics; Flavonoids	C57BL/6J mice (n = 50; Male; 5 months)	30–750 mg/kg/d (oral) for 3 weeks	Outcomes: ↑ Hepatic glycogen; ↓ BUN, Lactic acid; ↑ SOD, GSH-Px; ↓ MDA. Mechanism: Activation of Nrf2/ARE pathway (↑ Nq1, Gclc, Gclm).	Cui et al. (2020)
Fermented black soybean & adlay	Bacillus subtilis var. natto (28 °C; 43 h)	Nattokinase; γ-PGA; Phenolics	Aged C57BL/6J mice (n = 56; Male/Female; 48 weeks)	2 % or 6 % diet for 14 weeks	Outcomes: ↓ Muscle loss (Sarcopenia); ↓ Visceral fat; ↓ Pro-inflammatory cytokines. Mechanism: Microbiota modulation & reduction of hepatic oxidative stress markers.	Koh et al. (2023)
Tempeh	Rhizopus oligosporus (Solid-state; 37 °C; 5–7 d)	Aglycone isoflavones; Polyphenols	SAMP8 (Aging model) & SAMR1 mice (n = 58; Male; 6 months)	300–900 mg/kg BW/d for 12 weeks	Outcomes: ↑ Cognitive performance; ↓ Brain Aβ accumulation; ↓ Protein carbonyls. Mechanism: Nrf2 signaling activation and modulation of MAPK pathways.	Chan et al. (2018)
Fermented soy beverage	Bifidobacterium pseudocatenulatum INIA P815 (Anaerobic; 37 °C; 24 h)	Aglycone isoflavones (Genistein, Daidzein)	C57BL/6J mice (n = 96; Female; 10 months; Menopause model)	4 mL/day for 36 days	Outcomes: ↑ Isoflavone bioavailability; ↑ Reproductive health (cyclic mice); ↓ Serum triglycerides. Mechanism: Bio-conversion to aglycones rather than microbiota remodeling.	Ruiz de la Bastida et al. (2023)
Miso soup	Traditional fermentation (High salt)	Isoflavones; Melanoidins; Vitamins	Dahl salt-sensitive rats (n = 32; Male; 4 weeks)	10 % Miso soup (1.3 % NaCl) for 8 weeks	Outcomes: ↓ Salt-induced hypertension; ↓ Renal/Cardiac structural damage. Mechanism: Protection against salt-induced cardiovascular stress despite Na intake.	Yoshinaga et al. (2012)
Hawaijar	Mixed Bacillus spp. (Natural fermentation; 3–7 d)	Fibrinolytic enzymes; ACE-inhibitory peptides	Sprague–Dawley rats (Male; 6–8 weeks)	200 mg/kg BW/d for 4 weeks	Outcomes: ↑ Fibrinolytic activity; ↓ ACE activity; Improved lipid oxidation. Mechanism: Bioactive peptide-mediated cardiometabolic regulation.	Anand Singh et al. (2023)
Doenjang	Traditional aging (Long-term)	Aglycone isoflavones; Peptides	C57BL/6J mice (n = 47; Male; 4 weeks)	14.4 % freeze-dried Doenjang in HFD (11 weeks)	Outcomes: ↓ Neuronal loss; ↑ Neurogenesis; ↓ Aβ & Tau hyperphosphorylation. Mechanism: Inhibition of neuroinflammation and oxidative stress pathways.	Ko et al. (2019)
Co-fermented red bean extract	Bacillus subtilis & Lactobacillus bulgaricus (37 °C; 120 h)	Catechin; Rutin; Ferulic acid	C57BL/6 mice (n = 30; Male; 8 weeks) & Drosophila	Drosophila: 3.3–10 mg/mL (diet); Mice: 0.5 g/kg (15 d)	Outcomes: ↑ Motor function (Mice); ↑ Lifespan (Drosophila); ↑ GPx. Mechanism: Neuroprotection via antioxidant capacity and radical scavenging.	Chou et al. (2025)
Natto	Bacillus subtilis natto T9303 (39 °C; 20h + 4 °C; 24h)	Low-MW fraction (<14 kDa)	Caenorhabditis elegans N2 (Adult)	0.5–1 mg/mL water extract (22.5–25.5 d)	Outcomes: ↑ Lifespan; ↑ Thermotolerance; ↓ Lipofuscin accumulation. Mechanism: Activation of stress-response pathways (independent of spermidine).	Ibe et al. (2013)
Fermented mung bean	Rhizopus microsporus 5351 (Solid-state; 30 °C; 48 h)	GABA; Free amino acids; Phenolics	MCF-7 cells; Murine splenocytes (Ex vivo)	2–3 mg/mL (24–72 h)	Outcomes: ↑ Splenocyte proliferation (Immunomodulation); ↑ Cytokines (IL-2, IFN-γ). Mechanism: Cell-cycle arrest and apoptosis in cancer cells; Immune stimulation.	Ali et al. (2016)
Soymilk kefir	Kefir grains (Microbial consortium; 20 °C; 32 h)	Soy peptides; Isoflavones	Salmonella typhimurium TA98 (Mutagenicity assay)	10 mg/mL freeze-dried powder	Outcomes: ↑ Antimutagenic activity; ↑ Antioxidant capacity. Mechanism: Peptide-mediated radical scavenging (superior to unfermented milk).	Liu et al. (2005)

Abbreviations: ACE, angiotensin-converting enzyme; ApoB, apolipoprotein B; ARE, antioxidant response element; BP, blood pressure; BUN, blood urea nitrogen; d, day(s); DSS, dark soy sauce; GABA, gamma-aminobutyric acid; Gclc, glutamate-cysteine ligase catalytic subunit; Gclm, glutamate-cysteine ligase modifier subunit; h, hour(s); HFD, high-fat diet; IFN-γ, interferon gamma; kDa, kilodalton; MW, molecular weight; Nq1, NAD(P)H:quinone oxidoreductase 1; SAMP8, senescence-accelerated mouse prone 8; SAMR1, senescence-accelerated mouse resistant 1; y, years; γ-PGA, poly-gamma-glutamic acid.

2.3. Fermented cereal products

Cereal grains are considered staple foods on a global scale (Abdel-Aal, 2023), yet their nutritional potential is frequently constrained by the presence of anti-nutritional factors such as phytates and tannins (Samtiya et al., 2020). Fermentation, a process of biochemical breakdown, has been shown to yield a number of benefits for human health. These benefits include the production of beneficial compounds, a reduction in anti-nutrient content, and an enhancement of bioavailability, thereby improving nutritional value (Melini et al., 2019; T. Zhao et al., 2019, Zhao et al., 2019). Fermented cereal foods constitute a significant component of global food cultures, exhibiting a long historical presence and a diverse array of varieties (Petrova and Petrov, 2020). The primary fermented cereal foods encompass sweet pasta sauces, rice vinegar, rice wine, bread, and similar products. Fermented cereal products have emerged as a viable solution to address the mounting demand for healthy, nutritious, and low-fat or plant-based dietary patterns. These products are garnering increasing recognition as a pivotal category within the expanding functional food landscape (Tsafrakidou et al., 2020).

As outlined in Table 3, contemporary research, predominantly grounded in animal models and mechanistic studies, underscores the distinct anti-aging consequences of fermented cereal products in neuroprotection, metabolic regulation, and cellular longevity. In animal models, fermented cereal products have shown pronounced efficacy in alleviating neurodegenerative and metabolic aging phenotypes. Supplementation with Yellow Rice Wine significantly improved memory performance and fatigue resistance in D-galactose–induced aging mice (Liu et al., 2020), an effect mechanistically associated with the suppression of hippocampal neuronal apoptosis via regulation of the Bax/Bcl-2 ratio and Caspase-3 signaling. Similarly, Red Mold Rice fermented by Monascus purpureus reduced cerebral amyloid-β accumulation in hyperlipidemic rats by shifting amyloid precursor protein processing toward the non-amyloidogenic pathway (Lee et al., 2010). Beyond neuroprotection, fermented cereal products also exert beneficial metabolic and gut-related effects. Fermented wheat germ co-fermented with Lactobacillus plantarum and Saccharomyces cerevisiae enhanced learning and memory while increasing hepatic antioxidant enzyme activities (SOD and GSH-Px) in aging mice, with these effects closely linked to gut microbiota remodeling, suggesting involvement of the gut–brain axis (Y. Zhao et al., 2021). Concurrently, black vinegar extracts have been shown to ameliorate hyperlipidemia and systemic inflammation in hamsters fed a high-fat diet. This effect is attributed to a reduction in pro-inflammatory cytokines (TNF-α and IL-1β) and an enhancement of hepatoprotective antioxidant defenses (Chou et al., 2015). In mechanistic and lifespan models, specific fermentation metabolites have been identified as key drivers of longevity. Barathikannan et al. (2023) observed that fermented brown rice extracts extended the lifespan of Caenorhabditis elegans and reduced lipid accumulation by downregulating fatty acid desaturase genes. Furthermore, Luti et al. (2020) identified low-molecular-weight peptides (<3 kDa) in sourdough bread that exerted potent anti-inflammatory effects in macrophages by inhibiting the NF-κB signaling pathway.

Table 3.

Anti-aging effects of fermented cereal products.

Fermented Product	Microorganism & Fermentation Conditions	Key Bioactive Compound(s)	Experimental Model (n/Sex/Age)	Intervention (Dose & Duration)	Key Outcomes & Mechanisms	Reference
Fermented Wheat Germ	Lactobacillus plantarum + Baker's yeast; (28–37 °C; 18 h)	Ferulic acid; BCAAs; Peptides	BALB/c mice (n = 18; 6 weeks)	20 mg/kg/day for 6 weeks	Outcomes: ↑ Learning/memory; ↑ SOD, GSH-Px; ↓ MDA; ↑ Hepatic glycogen. Mechanism: Modulation of gut microbiota composition linked to metabolic regulation.	Y. Zhao et al. (2021)
Chinese Rice Wine	Mixed yeast; fungi; and LAB (Traditional starter)	Amino acids; GABA; Polysaccharides	Male Kunming mice (n = 40; Male; 12 weeks)	0.15–0.40 mL/day for 15–56 days	Outcomes: ↑ Hepatic glycogen; ↓ Blood lactic acid/BUN; ↑ SOD, GSH-Px, CAT; ↓ MDA. Mechanism: Enhanced antioxidant defense and energy metabolism.	Zhao et al. (2018)
Yellow Rice Wine	Traditional Qu (Semi-solid fermentation)	Functional oligosaccharides; Phenolics	Kunming mice (n = 120; Male; 12 weeks)	4–12 mL/kg BW/day for 6 weeks	Outcomes: ↓ Fatigue resistance; ↑ Memory performance; ↑ Antioxidant enzymes. Mechanism: Suppression of hippocampal neuronal apoptosis via Bax/Bcl-2 and Caspase-3 signaling.	Liu et al. (2020)
Red Mold Rice	Monascus purpureus NTU 568 (Solid-state)	Monacolin K; Secondary metabolites	Wistar rats (n = 49; 280–320g)	151–755 mg/kg/day for 28 days	Outcomes: ↑ Memory; ↓ Brain cholesterol; ↓ Aβ burden. Mechanism: Shift of APP processing toward non-amyloidogenic sAPPα pathway via inhibition of ApoE/β-secretase.	Lee et al. (2010)
Black Vinegar	Traditional surface fermentation	Amino acids; Minerals; Polyphenols	Golden Syrian hamsters (High-fat diet; n = 32; Male; 5 weeks)	0.13–0.26 g/kg BW/day for 9 weeks	Outcomes: ↓ Serum/Hepatic lipids; ↓ Inflammatory cytokines (TNF-α, IL-1β); ↑ Fecal lipid excretion. Mechanism: Combined hepatoprotective and antioxidant regulation.	Chou et al. (2015)
Rice Wine (Cheong-ju)	Koji and Yeast saccharification	Glycerol derivatives; Amino acids	Hairless mice (n = 15; Female; 6 weeks)	Topical application (2 %, daily) for 2 months	Outcomes: ↓ UV-induced oxidative stress; ↑ Skin barrier integrity; ↓ MMP-1 expression. Mechanism: Enhanced extracellular matrix synthesis (↑ Type I procollagen).	Seo et al. (2009)
Tapuy (Philippine Rice Wine)	Indigenous Bubod starter	Phenolic compounds	Caenorhabditis elegans (Wild-type N2; L4 stage)	5000–50,000 μg/mL in growth medium	Outcomes: Modest lifespan extension (+6.1 % at high dose). Mechanism: Dissociation between antioxidant capacity and longevity effects (non-antioxidant pathway).	Chua et al. (2024)
Fermented Brown Rice	Pediococcus acidilactici MNL5 (Solid-state; 37 °C; 24h)	Ferulic acid	C. elegans (N2 & daf-2 mutants)	1 mg/mL extract	Outcomes: ↑ Lifespan (Wild-type & daf-2); ↓ Lipid accumulation. Mechanism: Downregulation of fatty acid desaturase genes (fat-4, fat-5, fat-6).	Barathikannan et al. (2023)
Tempeh-like Chenopodium	Rhizopus microsporus var. Oligosporus(35 °C; 4 d)	Glycine-rich peptide (GRP)	C. elegans (N2) & Human fibroblasts	50–100 μg/mL (GRP)	Outcomes: ↑ Lifespan; ↑ Stress resistance; ↓ Cellular senescence. Mechanism: Activation of Nrf2-dependent pathway and upregulation of skn-1 (ortholog of Nrf2).	Hsieh et al. (2025)
Sourdough Bread	Selected Lactobacillus spp. (30 °C; 18h)	Low-MW peptides (<3 kDa)	RAW 264.7 murine macrophages	0.01 mg/mL peptides (1 h pretreatment)	Outcomes: ↓ Intracellular ROS; ↓ iNOS and COX-2 expression. Mechanism: Inhibition of NF-κB signaling via stabilization of IκB.	Luti et al. (2020)
Fermented Rice Bran	Issatchenkia orientalis (35 °C; 5 d)	Ferulic acid derivatives	3T3-L1 adipocytes	10–50 μg/mL extract	Outcomes: ↓ Oxidative stress-induced ROS; ↑ PPAR-γ, Adiponectin. Mechanism: Regulation of adipogenesis and inflammation-related gene expression.	Kim and Han (2011)
Commercial Beers	Saccharomyces cerevisiae + Saccharomyces carlsbergensis (3–20 °C; 4–12 weeks)	Catechin; Caffeic acid	Isolated thoracic aorta rings from male Wistar rats (10–12 weeks)	Cumulative concentrations	Outcomes: ↑ Endothelium-dependent vasorelaxation; ↑ Antioxidant capacity. Mechanism: Nitric oxide (NO) signaling pathway modulation.	Oliveira Neto et al. (2017)
Fermented Buckwheat Flour	L. rhamnosus; S. thermophilus; R. oligosporus	Phenolic compounds	In vitro simulated digestion model	10 g freeze-dried product	Outcomes: ↑ Bioaccessibility of phenolics; ↑ Anti-AGEs activity. Mechanism: Digestion-dependent release of functional phenolics.	Zieliński et al. (2020)
Boza	Mixed yeast and LAB (Traditional)	ACE-inhibitory peptides (<10 kDa)	In vitro simulated digestion model	N/A	Outcomes: Strong ACE-inhibitory activity. Mechanism: Production of bioactive low-MW peptides during fermentation.	Kancabaş and Karakaya (2013)
Shanxi Aged Vinegar	Traditional solid-state fermentation	Melanoidins; Polyphenols	In vitro antioxidant assays	N/A	Outcomes: High antioxidant activity (ABTS, FRAP). Mechanism: Correlation between aging time and accumulation of melanoidins/phenolics.	Xia et al. (2018)

Abbreviations: AGEs, advanced glycation end-products; ApoE, apolipoprotein E; APP, amyloid precursor protein; Bax, Bcl-2-associated X protein; BCAAs, branched-chain amino acids; Bcl-2, B-cell lymphoma 2; COX-2, cyclooxygenase-2; daf-2, abnormal dauer formation-2 (insulin/IGF-1 receptor homolog); FRAP, ferric reducing antioxidant power; GRP, glycine-rich peptide; IκB, inhibitor of nuclear factor kappa B; iNOS, inducible nitric oxide synthase; MMP-1, matrix metalloproteinase-1; NF-κB, nuclear factor kappa B; PPAR-γ, peroxisome proliferator-activated receptor gamma; sAPPα, soluble amyloid precursor protein alpha; UV, ultraviolet.

2.4. Other fermented products

Fermented foods have been consumed globally for millennia, exhibiting remarkable diversity in terms of raw materials, microbial communities, and processing strategies (Rul et al., 2022). In addition to the extensive research conducted on dairy, soy, and cereal-based products (Lindner and Bernini, 2022), a mounting body of evidence suggests that fermented vegetables, fruits, teas, medicinal herbs, and animal-derived products may also offer anti-aging benefits through conserved molecular mechanisms (Das et al., 2020; Zhang et al., 2022). The primary anti-aging value of these products is attributable to the microbial biotransformation of substrate-specific phytonutrients. Fermentation is a process that has been shown to effectively convert conjugated phenolic compounds into bioactive aglycones and synthesize novel metabolites. These metabolites include theabrownin and microbial exopolysaccharides. The result of this process is an enhancement of the bioavailability and functional potency of the compounds compared to their unfermented counterparts (Rajendran et al., 2023; Yuan et al., 2023, 2024).

As outlined in Table 4, a wide array of these fermented products has exhibited substantial anti-aging potential, encompassing effects on skin health and metabolic regulation. In human clinical trials, fermentation-derived metabolites have demonstrated potential in mitigating skin aging. Chan et al. (2021) conducted a randomized trial involving a fermented vegetable-fruit drink (fermented by Saccharomyces cerevisiae and Streptococcus thermophilus). After 8 weeks of supplementation, healthy adults exhibited significantly increased systemic antioxidant capacity (SOD, CAT) and improved skin elasticity, accompanied by a reduction in wrinkles and spots. In the context of animal models, Lei et al. (2022) demonstrated that Pu-erh tea, which is abundant in theabrownin polyphenol, exhibited a positive effect on cognitive functions, specifically learning and memory, in mice subjected to D-galactose-induced aging. This neuroprotective effect was achieved by modulating the gut–liver–brain axis, specifically through the enrichment of Akkermansia muciniphila. Similarly, Cardoso et al. (2021) found that Kombucha (fermented black/green tea) alleviated hepatic steatosis and insulin resistance in rats by regulating lipid metabolism genes (e.g., SREBP-1c, CPT-1). Logozzi et al. (2020) provided compelling evidence that a Fermented Papaya Preparation (FPP) modulated redox balance in aging mice. It is important to note that this intervention led to the induction of a “pro-longevity” molecular signature, as evidenced by an increase in telomere length and telomerase activity in bone marrow and ovarian cells. Wang et al. (2022) reported that fermented Lycium barbarum (Wolfberry) polysaccharides significantly extended the lifespan of Caenorhabditis elegans and enhanced stress resistance via the activation of the DAF-16/FOXO pathway, independent of insulin signaling. In vitro investigations have elucidated the cellular mechanisms that are unique to fermented vegetables and animal products. Kim et al. (Kim et al., 2011) investigated the properties of kimchi, and specifically its extracts from “optimally ripened” kimchi (pH 4.2). They found that these extracts extended the replicative lifespan of human fibroblasts and suppressed stress-induced premature senescence by inhibiting NF-κB signaling. In addition, Park et al. (2018) demonstrated that fermented fish oil provided superior photoprotection in comparison with unfermented DHA/EPA. This superiority was evidenced by the effective inhibition of UVB-induced apoptosis in keratinocytes through MAPK pathway modulation.

Table 4.

Anti-aging effects of other fermented products.

Fermented Product	Microorganism & Fermentation Conditions	Key Bioactive Compound(s)	Experimental Model (n/Sex/Age)	Intervention (Dose & Duration)	Key Outcomes & Mechanisms	Reference
Fermented Veg-Fruit Drink	S. cerevisiae + S. thermophilus TCI125 (35 °C; 10 d)	Polyphenols; SOD-like enzymes	Healthy humans (n = 30; 13Male/17Female; 35–55 y)	50 mL/day for 8 weeks	Outcomes: ↑ Systemic antioxidant status (SOD, CAT); ↑ Skin elasticity/moisture; ↓ Wrinkles/Spots. Mechanism: Enhanced collagen synthesis and systemic redox defense.	Chan et al. (2021)
Malus micromalus Makino fruit wine	Yeast-mediated fruit fermentation	Polysaccharides (MWP-2); Phenolics	Kunming mice (n = 60; half male, half female; 6 weeks)	50–150 mg/kg BW/day for 4 weeks	Outcomes: ↓ Brain lipid peroxidation; ↓ Neuronal apoptosis; ↑ SOD, GPx, CAT. Mechanism: Polysaccharide-mediated redox regulation and neuroprotection.	Hui et al. (2019)
Pu-erh Tea	Microbial solid-state fermentation	Theabrownin (TB)	C57BL/6 mice (n = 40; Male; 5–6 weeks)	1.2 g/kg BW (TB) for 8 weeks	Outcomes: ↑ Learning/memory; ↓ Systemic inflammation (IL-6, TNF-α); ↑ Intestinal barrier. Mechanism: Gut-liver-brain axis remodeling (↑ Akkermansia, ↓ E. coli).	Lei et al. (2022)
Fermented Papaya	Yeast fermentation (10 months)	Antioxidants (Ascorbic acid)	C57BL/6J mice (n = 40; Female; 4 weeks)	6 mg/mouse/day (water) long-term	Outcomes: ↑ Telomere length (Bone marrow/Ovaries); ↑ Telomerase activity; ↓ ROS. Mechanism: Time-dependent redox balance and telomere maintenance.	Logozzi et al. (2020)
Kombucha (Green/Black Tea)	Symbiotic Culture of Bacteria and Yeast (25 °C; 10 d)	Catechins; Phenolic acids	Wistar rats (n = 32; Male; 45–50 d)	30 % (v/v) drink for 10 weeks	Outcomes: ↓ Insulin resistance; ↓ Hepatic steatosis; ↑ SOD, CAT; ↓ NLR (Inflammation). Mechanism: Coordinated regulation of lipid metabolism genes (↓ SREBP1c, ↑ CPT-1).	Cardoso et al. (2021)
Haihong Fruit Wine	Commercial fruit wine (∼10 % v/v alcohol)	Polyphenols; Flavonoids; Triterpenoids; Phytosterols	Kunming mice (n = 60; 30Male/30Female; 20–25 g)	0.075–0.30 mL/10 gBW/day for 42 days	Outcomes: ↑ Systemic antioxidant defense (SOD, CAT, GPx); ↓ Lipid peroxidation (MDA) in liver and brain. Mechanism: Polyphenol-mediated ROS scavenging and membrane protection.	Hui et al. (2021)
Black Tea Extract	Commercial CTC-grade	Theaflavins	Wistar rats (n = 48; Male; Young to Old)	1 mL/100g BW/day for 30 days	Outcomes: ↑ Plasma FRAP; ↑ Erythrocyte GSH; ↓ MDA/AOPPs. Mechanism: Theaflavin-mediated mitigation of age-related oxidative stress.	Kumar and Rizvi (2017)
Fermented Green Tea	Aspergillus niger (30 °C; 4 d)	Catechins; Proanthocyanidins; L-theanine	Caenorhabditis elegans (N2 wild-type)	10 % extract in medium	Outcomes: ↑ Lifespan; ↑ Locomotion; ↑ Mitochondrial function. Mechanism: Activation of DAF-16, HSF-1, and p53 signaling pathways.	Liu et al. (2025)
Probiotic Fermented Ginseng	lactic acid bacteria and yeast	Ginsenoside metabolites	Caenorhabditis elegans (Wild-type N2; L4 stage)	0–160 μg/mL	Outcomes: ↑ Lifespan; ↑ Thermal/Oxidative tolerance; ↓ Apoptosis. Mechanism: IIS pathway modulation (↓ daf-2, ↑ skn-1, ↑ sod-3).	Xu et al. (2023)
Dragon Fruit-Kiwi Beverage	S. cerevisiae Y1 + L. mesenteroides + S. thermophilus (30–37 °C; 9–15 d)	GABA; Phenolics; Riboflavin	Caenorhabditis elegans (N2 wild-type)	1.56 % (v/v) in medium	Outcomes: ↑ Lifespan (∼18 %); ↑ SOD; ↓ MDA. Mechanism: GABA/Phenolic-mediated redox regulation.	Tang et al. (2022)
Fermented Lycium barbarum (Wolfberry)	Rice wine yeast (28 °C; 36 h)	Lycium barbarum polysaccharide (LBP-Y)	Caenorhabditis elegans N2 (Synchronized; ∼50/group)	0.1–1.0 mg/mL (Lifespan); 1.0 mg/mL (Stress assays)	Outcomes: ↑ Lifespan under normal/oxidative/heat stress; ↑ Radical scavenging & T-AOC. Mechanism: Activation of stress-response genes (↑ daf-16, sod-3, hsp-16.2) independent of daf-2 signaling.	Wang et al. (2022)
Fermented Purple Sweet Potato	Weissella confusa NJLY1 (37 °C; 24 h)	Anthocyanins; Phenolic acids	Caenorhabditis elegans (N2; >30 worms)	80 μg/mL anthocyanins	Outcomes: ↑ Lifespan vs. non-fermented; ↓ Lipofuscin. Mechanism: Activation of DAF-16/FOXO, SKN-1/Nrf2, and SIR-2.1 pathways.	(J. Zhao et al., 2021)
Kimchi (Optimally Ripened)	Traditional lactic acid fermentation at 5 °C to pH 4.2	Organic acids; Phytochemical metabolites	WI-38 human fibroblasts (Aging models)	100 μg/mL extract (24 h pre-treat)	Outcomes: ↑ Replicative lifespan; ↓ Lipid peroxidation; ↑ Cell viability. Mechanism: Suppression of NF-κB activation (↓ nuclear NF-κB, iNOS, COX-2).	Kim et al. (2011)
Solar Salts Kimchi	Traditional lactic acid bacteria fermentation	Phenolics; Flavonoids	RAW 264.7 macrophages	2.5 mg/mL (24 h)	Outcomes: ↑ Antioxidant capacity (FRAP); ↓ Inflammatory cytokines (IL-1β, IL-6, TNF-α). Mechanism: Stronger anti-inflammatory effects in optimally ripened variants.	Yun et al. (2023)
Fermented Lespedeza cuneata	Lactobacillus pentosus (37 °C; 5 d)	Aglycone flavonoids (Kaempferol, Quercetin)	Hs68 human fibroblasts	100–400 μg/mL (48 h)	Outcomes: ↑ Elastase inhibition; ↑ Type I procollagen; ↓ UV-induced MMP-1. Mechanism: β-glucosidase-mediated conversion to bioactive aglycones.	Seong et al. (2017)
Jeju Citrus Vinegar	S. cerevisiae + A. pasteurianus (25–35 °C; 22 d)	Flavonoids (Hesperidin)	3T3-L1 adipocytes; WI-38 fibroblasts	1/100 dilution (24 h–8 days)	Outcomes: ↓ Lipid accumulation; ↓ Senescence-associated genes (p21, p53). Mechanism: Downregulation of adipogenic regulators (PPARγ, C/EBPα).	Yun et al. (2021)
Fermented Meat (Slavonian Kulen)	Lactiplantibacillus plantarum 1K(37 °C; 48 h)	Metabolites <2 kDa	Human PBMCs (Male donor)	Metabolites (10 ng/mL) (4 h)	Outcomes: ↓ TNF-α secretion (∼70 %); High DPPH scavenging. Mechanism: Immunomodulation by small microbial metabolites without cytotoxicity.	Kostelac et al. (2022)
Fermented Fish Oil	L. plantarum + S. cerevisiae (30 °C; 15 d → 18–20 °C; 50 d)	EPA; DHA; Fatty acids	HaCaT keratinocytes; HR-1 hairless mice (n = 20; Male, 7 weeks)	In vitro: 10–50 μg/mL, 24 h; In vivo: topical 2 or 20 mg/mL, 2 weeks	Outcomes: ↓ UVB-induced apoptosis (↑ Bcl-2/Bax); ↓ MAPK signaling. Mechanism: Synergistic photoprotection greater than DHA alone.	Park et al. (2018)

Abbreviations: AOPPs, advanced oxidation protein products; C/EBPα, CCAAT/enhancer-binding protein alpha; CPT-1, carnitine palmitoyltransferase-1; CTC, crush, tear, curl (tea processing grade); DHA, docosahexaenoic acid; DPPH, 2,2-diphenyl-1-picrylhydrazyl; EPA, eicosapentaenoic acid; FOXO, forkhead box O; HSF-1, heat shock factor 1; hsp, heat shock protein; NLR, neutrophil-to-lymphocyte ratio; PBMCs, peripheral blood mononuclear cells; SREBP1c, sterol regulatory element-binding protein 1c; TB, theabrownin; UVB, ultraviolet B.

3. Mechanism of the anti-aging effects of fermented foods

The pursuit of healthy aging has led to a heightened interest in natural, safe, and effective dietary interventions. Fermented foods, defined as food matrices that have undergone a process of transformation by the enzymatic activity of microorganisms that are beneficial to health, have emerged as a potent functional food category, a notion that is supported by a growing body of evidence (Dimidi et al., 2019; Ibrahim et al., 2023) The anti-aging efficacy of these foods stems from a fundamental bioconversion process involving the degradation of anti-nutritional factors (e.g., flatulence-causing oligosaccharides) (Mollakhalili-Meybodi et al., 2022) and the simultaneous biosynthesis of health-promoting metabolites, such as lactic acid, bioactive peptides, and enhanced phenolic compounds (Gopikrishna et al., 2021). Beyond improving nutritional bioavailability, fermented foods exhibit pleiotropic biological activities, including antioxidant, antimicrobial, and immunomodulatory effects(Hasegawa and Bolling, 2023). Moreover, they play a pivotal role in systemic metabolic regulation, including the reduction of cholesterol and the modulation of the gut microbiota to prevent chronic age-related diseases (Thumu and Halami, 2020). The aforementioned benefits are attributable to the synergistic action of viable probiotics and their functional metabolites(Mahamud et al., 2025). As demonstrated in Fig. 4, the underlying molecular mechanisms are intricate and interconnected, primarily involving the mitigation of oxidative stress, the regulation of apoptotic and autophagic pathways, the enhancement of immune function, and the restoration of gut dysbiosis.

Fig. 4.

Anti-aging mechanisms of fermented foods.

3.1. Mitigation of oxidative stress

Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and the ability of cells to maintain their structural and functional integrity, is a major contributing factor to the aging process and the development of age-related metabolic abnormalities (Luo et al., 2021). While endogenous antioxidants have been shown to counteract this damage, their capacity declines with age. Fermented foods have therefore received significant attention for their potential to mitigate oxidative stress through bioactive compounds derived from fermentation. The fermentation process has been shown to enrich foods with hydrolyzed antioxidant peptides, free amino acids, and free polyphenols. These bioactive compounds function through two distinct mechanisms: (1) Direct Scavenging: These enzymes have been observed to facilitate the chelation of metal ions, engage in the direct scavenging of free radicals through proton or hydrogen donation, and inactivate singlet oxygen (Chen et al., 2023). (2) Enzymatic Regulation: These substances have been shown to modulate the host's endogenous defense systems by stimulating the secretion of key antioxidant enzymes, including SOD, CAT, HO-1, and GSH-Px (Zheng et al., 2023). The mechanisms in question are illustrated by specific fermented products. For instance, in vitro and animal studies suggest that kimchi retards the progression of aging by diminishing the production of free radicals and augmenting antioxidant enzyme activity (Kim et al., 2011). Furthermore, the fermentation of grains (e.g., buckwheat, barley) has been demonstrated to markedly augment phenolic and flavonoid content, consequently enhancing DPPH radical scavenging capacity and FRAP activity in comparison to unfermented controls (Bhanja Dey and Kuhad, 2014).

3.2. Regulation of apoptosis

Apoptosis, a fundamental physiological process, is dysregulated in cases of accelerated tissue aging. Fermented foods have been demonstrated to exert a protective effect against age-related cellular loss by modulating apoptotic signaling pathways. Bioactive components that are enriched during the fermentation process have been shown to safeguard the intracellular environment by restoring the balance between pro-apoptotic and anti-apoptotic factors (Calabrò et al., 2024). In animal models, fermentation-derived metabolites have been demonstrated to directly target the Bcl-2 and Caspase families. Specifically, interventions with fermented products have been shown to downregulate the expression of the pro-apoptotic protein Bax and the executioner protease Caspase-3, while simultaneously upregulating the anti-apoptotic protein Bcl-2. This shift has been demonstrated to impede the cleavage of cellular substrates and to inhibit the initiation of programmed cell death (Q. Y. Gong et al., 2022; Xu et al., 2019). Furthermore, fermentation bioactives have been demonstrated to play a critical role in the SIRT1-p53 axis. In contrast to the age-related decline in sirtuin activity, fermentation-derived polyphenols and peptides have been shown to activate SIRT1, which subsequently deacetylates and inhibits the oncogenic protein p53, thereby decreasing apoptotic susceptibility and extending cellular lifespan (Chen et al., 2017; Ou and Schumacher, 2018). The validation of this mechanism in vivo has been demonstrated by studies that have shown that probiotics, active peptides, and resveratrol, which are enriched in fermented foods, significantly downregulated the mRNA expression of p53, NF-κB, and Caspase-3 in the brain tissue of aged mice. Concurrently, these interventions have been shown to enhance the expression of neuroprotective factors, such as Nrf2 and Bcl-2, thereby effectively mitigating neuronal apoptosis and preserving cognitive function (Y. Wang et al., 2020; Xia et al., 2020).

3.3. Activation of autophagy

Autophagy is a critical cellular renewal process where cells degrade damaged organelles and misfolded proteins to maintain homeostasis. The decline of autophagic capacity is a hallmark of aging, leading to the accumulation of cellular debris, mitochondrial dysfunction, and chronic inflammation (Deretic, 2021). Fermented foods have been shown to intervene in this process primarily by modulating nutrient-sensing signaling pathways. In both animal and cellular models, the anti-aging effects of fermented foods have been demonstrated to be closely linked to the activation of AMPK (adenosine monophosphate-activated protein kinase) (Hofer et al., 2022). AMPK functions as a central energy sensor that, upon activation, triggers autophagy to restore energy homeostasis. A body of research has indicated that specific probiotics and bioactive metabolites isolated from fermented foods can significantly increase AMPK phosphorylation levels (Hor et al., 2019; Jang et al., 2019). This activation promotes autophagic flux, thereby reducing oxidative stress and enhancing metabolic resilience during aging (Wang et al., 2019). Conversely, the mTOR (mammalian target of rapamycin) pathway, which functions as a negative regulator of autophagy, is often hyperactive in aging tissues. Mechanistic studies suggest that fermentation-derived polyphenols can effectively inhibit mTOR signaling (Liu and Sabatini, 2020). The suppression of mTOR and the concomitant activation of AMPK by these bioactive compounds induce a pro-autophagic state, thereby facilitating cellular rejuvenation (R. Gong et al., 2022). Moreover, this regulatory framework frequently intersects with the insulin/IGF-1 signaling (IIS) pathway(Kim and Lee, 2019) and the Sirtuin pathway (Jiang et al., 2025). Collectively, improving autophagic capacity through fermented food interventions represents a vital strategy for maintaining cellular metabolic balance and ameliorating pathological aging.

3.4. Enhanced immunity

Immunosenescence, defined as the gradual decline of both adaptive and innate immunity, plays a substantial role in the development of age-related diseases. Fermented foods have been demonstrated to offer a nutritional strategy to counteract this decline by modulating immune cell activity and cytokine profiles (Salminen et al., 2019; Sanyal and Haldar, 2025). In animal models, probiotics isolated from fermented foods (e.g., Lactobacillus plantarum, Lactobacillus helveticus, and Lactobacillus pentosus) have demonstrated potent immunomodulatory properties. The efficacy of these strains in enhancing the phagocytic activity of macrophages and restoring the homeostatic balance of T lymphocytes has been demonstrated, as evidenced by the increase in the numbers of naïve CD4⁺ and CD8⁺ T cells (J. Wang et al., 2020; You et al., 2020). Mechanistically, these interventions promote the expression of immunostimulatory cytokines (e.g., NO, IL-2, IL-6) while simultaneously suppressing pro-inflammatory mediators like TNF-α, thereby enhancing resistance to pathogens (Agrawal et al., 2017; Wastyk et al., 2021; You et al., 2020). Beyond viable bacteria, bioactive metabolites generated during fermentation play a crucial role. As stated by Badr et al. (2012), an increase in the proliferative capacity of lymphocytes and monocytes in response to antigenic stimuli was observed following the administration of fermented whey protein concentrates. In addition, fermentation-derived polyphenols and polysaccharides have been shown to facilitate the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, and to promote the differentiation of immune-tolerant dendritic cells. These cellular shifts effectively mitigate chronic low-grade inflammation and decelerate organismal aging (Sun et al., 2022; Wang et al., 2024).

3.5. Relieve inflammation

“Inflammaging,” a term denoting the chronic, sterile, low-grade inflammation associated with the aging process, has been identified as a central driver of organismal degeneration (Picca and Marzetti, 2023). Fermented foods have been demonstrated to intervene in this process by reducing pro-inflammatory cytokines and reinforcing mucosal barriers to prevent systemic immune activation. In human clinical trials, evidence has emerged to support the systemic anti-inflammatory potential of fermented interventions. A meta-analysis by Gui et al. (Gui et al., 2020; Varsha et al., 2022) confirmed that the ingestion of fermented foods significantly enhances NK cell activity, suggesting that this dietary intervention may bolster immune surveillance, thereby preventing chronic inflammatory accumulation. Moreover, the maintenance of epithelial barrier integrity is paramount. As Polo et al. (2023) noted, the incorporation of fermented matrices aids in preserving tight junctions, thereby mitigating the systemic influx of endotoxins (“leaky gut”) that often precipitates inflammation in aged populations. In cellular and animal models, specific fermentation-derived metabolites have been demonstrated to modulate intracellular signaling pathways. As demonstrated by Gabriele et al. (2023), extracts from fermented dough exerted anti-inflammatory effects by activating the Nrf2/HO-1 signaling pathway, effectively coupling antioxidant defense with the suppression of inflammatory mediators. In a similar manner, the consumption of fermented soy products has been demonstrated to impede the generation of pro-inflammatory cytokines, such as MIF and IL-1β, and to diminish the infiltration of inflammatory cells. This effect is achieved through the repression of oxidative stress markers (Das et al., 2022). The bioactive compounds that are enriched during fermentation, including lovastatin and theabrownine in fermented tea, also play a mechanistic role. Deng et al. (2021) reported that these molecules significantly reduce TNF-α expression and promote the apoptosis of pro-inflammatory macrophages, thereby disrupting the vicious cycle of inflammation and senescence.

3.6. Regulate gut microbiota

Aging is frequently accompanied by gut dysbiosis, characterized by a decrease in microbial diversity, a reduction in beneficial genera, and an enrichment of pro-inflammatory pathobionts. This imbalance disrupts intestinal barrier function and accelerates systemic aging (Chao et al., 2025). Fermented foods intervene in this process through a dual mechanism involving the colonization of viable probiotics and the supply of postbiotic nutrients (Funk et al., 2020; Liu et al., 2021; Schluter et al., 2020). In animal models, specific probiotic strains isolated from fermented foods have demonstrated the capacity to reverse age-related dysbiosis. As demonstrated by Bu et al. (2023), the oral administration of Lactobacillus plantarum YRL45 to mice resulted in a substantial remodeling of the gut microbiota composition. Specifically, the intervention led to an enrichment of beneficial taxa, including Akkermansia muciniphila and Mycobacterium anisopliae, while concomitantly suppressing the proliferation of potentially harmful Clostridium spp. This microbial shift was accompanied by an increase in the production of SCFAs (short-chain fatty acids), specifically acetic and propionic acid. These SCFAs have been shown to enhance the phagocytic activity of macrophages and thereby promote resistance to intestinal inflammation (Brasiel & Potente Dutra Luquetti, 2025). Beyond viable bacteria, the fermentation matrix itself, which is abundant in vitamins and exopolysaccharides, plays a critical role in restoring homeostasis. According to Zhang et al. (2017), the consumption of Tibetan kefir in mice resulted in enhanced evenness and diversity of the intestinal flora. The ecological restoration demonstrated efficacy in reducing fecal nitrogen oxide levels and alleviating intestinal oxidative stress. Furthermore, fermentation-derived SCFAs have been shown to reinforce the intestinal mucosal layer and regulate glucose and lipid metabolism, thereby mitigating insulin resistance and metabolic disorders associated with aging (Fantini et al., 2023; Verediano et al., 2021).

3.7. Integrated network and synergistic mechanisms

Despite being presented as discrete biological processes in Sections 3.1–3.6, these mechanisms function within a highly interconnected regulatory network rather than independently. Aging is increasingly recognized as a multifactorial process driven by reciprocal interactions among oxidative stress, chronic low-grade inflammation, and metabolic dysregulation (López-Otín et al., 2023). Consequently, the anti-aging effects of fermented foods are more plausibly attributed to their coordinated modulation of these interdependent signaling pathways, rather than the regulation of any single mechanism alone, as schematically summarized in Fig. 5.

Fig. 5.

Anti-aging mechanism and related signaling pathways of fermented food.

The modulation of the gut ecosystem appears to function as a pivotal upstream regulatory event. The enrichment of beneficial microbial taxa, such as Lactobacillus and Akkermansia, in conjunction with the enhanced production of SCFAs, contributes to the reinforcement of intestinal epithelial barrier integrity. This, in turn, limits the translocation of bacterial endotoxins, particularly lipopolysaccharide, into systemic circulation. This effect attenuates a major initiating factor of chronic low-grade inflammation and, indirectly, reduces peripheral oxidative stress (Franceschi et al., 2018; Vaiserman et al., 2017). Research has demonstrated that bioactive compounds derived from fermented foods possess the capacity to disrupt the self-amplifying cycle between oxidative stress and inflammation. At the mechanistic level, direct scavenging of ROS, in conjunction with the activation of Nrf2-dependent antioxidant defenses, results in the suppression of downstream activation of the pro-inflammatory NF-κB signaling pathway. Concurrently, the attenuation of inflammatory cytokine production has been shown to reduce intracellular ROS generation, thereby disrupting the feed-forward loop that drives cumulative cellular damage during aging (Gao et al., 2022). Metabolic signaling also serves as a critical interface linking redox homeostasis to cellular quality control mechanisms. Fermentation-derived bioactive compounds, including polyphenols and bioactive peptides, have been demonstrated to modulate central energy sensors such as AMPK and SIRT1. The activation of these pathways has been shown to suppress mTOR signaling, thereby promoting autophagy-mediated clearance of damaged organelles. Concurrently, this process limits premature apoptosis through SIRT1-dependent deacetylation of p53 (Yang et al., 2025).

In summary, the evidence suggests that the consumption of fermented foods may offer benefits that contribute to a healthier, longer life. These effects appear to be the result of a coordinated, multi-target mode of action, encompassing modulation of the gut ecosystem to limit systemic inflammatory triggers, attenuation of the reciprocal amplification between oxidative stress and inflammation, and regulation of cellular longevity pathways via key metabolic sensors.

4. Current challenges and limitations

A mounting body of evidence suggests that the consumption of fermented foods may offer benefits that promote healthy aging. However, it is imperative to address the challenges and safety concerns associated with this practice to ensure that any potential benefits are not outweighed by unintended risks. Of particular concern are the presence of antinutritional factors and fermentation-associated byproducts. Fermentation has been demonstrated to be an effective method for reducing antinutritional components, such as phytates, trypsin inhibitors, and tannins, that are present in raw legumes and cereals (Sharma, 2021). However, the efficiency of antinutritional factor degradation is contingent upon the microbial strains employed, the nature of the substrate, and the specific fermentation conditions. Suboptimal or insufficiently controlled fermentation processes may therefore lead to the persistence of residual antinutritional components, which can compromise mineral bioavailability and protein digestibility. This is a particularly salient issue for older adults with compromised gastrointestinal function (Salim et al., 2023). Furthermore, spontaneous or uncontrolled fermentation has been shown to increase the risk of contamination by undesirable microorganisms, potentially leading to the formation of mycotoxins (e.g., aflatoxins) or excessive accumulation of biogenic amines such as histamine and tyramine (Saha Turna et al., 2024). Elevated concentrations of these amines, frequently reported in aged cheeses and certain fermented soy products, have been linked to adverse physiological responses, including headaches, elevated blood pressure, and pseudo-allergic reactions. Such effects may pose additional concerns for older individuals, particularly those with pre-existing cardiovascular susceptibility.

The high sodium content of many traditional fermented foods represents a significant limitation. A considerable proportion of products, including pickled vegetables (e.g., kimchi and sauerkraut) and fermented condiments such as soy sauce, depend on elevated salt concentrations to ensure microbial stability and product safety during fermentation and storage (Fitsum et al., 2025). Excessive sodium intake is a well-recognized risk factor for hypertension, cardiovascular disease, and gastric disorders. In the context of aging populations, the prolonged ingestion of high-salt fermented foods has the potential to mitigate their anticipated health benefits, thereby augmenting the cardiovascular strain. Consequently, the development and validation of low-salt or salt-reduced fermentation strategies have emerged as a significant technological and nutritional priority for the sustainable application of fermented foods in healthy aging.

The limited standardization and reproducibility of fermented foods constitute additional barriers to their translational application as anti-aging interventions. It is well established that traditional fermentation processes are inherently variable, often exhibiting pronounced batch-to-batch differences in microbial composition and metabolite profiles. This variability can lead to inconsistent bioactive properties (Tamang et al., 2017). This variability leads to inconsistent concentrations of bioactive compounds, which complicates the definition of standardized intake levels, the establishment of clear dose–response relationships, and the reproducibility of reported health outcomes. Collectively, these limitations hinder the incorporation of fermented foods into evidence-based nutritional guidelines and clinical recommendations (Hernández-Velázquez et al., 2024).

5. Conclusion and prospect

The deliberate extension of health span has long been a central objective in biomedical and nutritional research. In the context of a rapidly aging global population, there has been an increasing focus on food-based strategies, with fermented foods emerging as a particularly promising category. The evidence synthesized in this review indicates that the consumption of fermented foods may exert anti-aging effects primarily through the attenuation of oxidative stress, modulation of inflammatory responses and immune function, preservation of cellular homeostasis, and regulation of gut microbiota composition. The beneficial effects of this process are largely attributed to the synergistic actions of viable microorganisms and fermentation-derived bioactive compounds, including organic acids, phenolic metabolites, polysaccharides, and bioactive peptides.

Despite these encouraging findings, the extant evidence base remains heterogeneous, and a comprehensive understanding of how fermented foods influence aging processes is still incomplete. In light of the strengths and limitations identified in this review, the following research priorities are proposed for future investigation:

• (1)Mechanistic Elucidation via Multi-Omics. Future research should prioritize causal mechanistic validation by integrating genetic manipulation with multi-omics approaches to clarify how fermentation-derived components regulate key longevity-related pathways, particularly Nrf2-driven antioxidant defense, AMPK-mediated metabolic control, and sirtuin signaling (SIRT1/SIRT3).
• (2)Deciphering interactions within complex food matrices. Fermented foods are intricate matrices in which peptides, phenolics, and microbes interact. It is imperative to methodically examine whether these components manifest synergistic or antagonistic effects on aging endpoints through component fractionation and recombination experiments, as opposed to studying isolated compounds in a vacuum.
• (3)Strengthening translational and clinical evidence. These trials must incorporate validated aging biomarkers, such as oxidative stress indices, inflammatory cytokines, and cognitive functional endpoints, while accounting for inter-individual variability in metabolism.
• (4)Cautious advancement toward personalized nutrition. Despite the nascent state of personalized nutrition research, future studies may integrate dietary interventions with microbiota and metabolic profiling to identify response patterns. This integration has the potential to inform stratified rather than universal dietary recommendations.
• (5)Evidence-guided innovation in fermentation technology. The potential of synthetic ecology advancements should be exploited to enhance the efficacy of starter cultures. The objective is to enhance product consistency and safety by mitigating risk factors (e.g., biogenic amines, excessive salt) while maximizing the bioavailability of anti-aging bioactives.

In summary, the consumption of fermented foods is associated with numerous health benefits, including the potential to support healthy aging. To realize this potential, a shift toward mechanism-driven research, rigorous clinical validation, and evidence-based technological innovation is necessary. This will establish a solid scientific foundation for the rational development of fermented food–based strategies for healthy aging.

Data availability statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

CRediT authorship contribution statement

Hongyu Mu: Writing–original draft. Yeyan Yao: Methodology. Yongqiang Gong: Writing–review & editing. Tao Yang: Supervision.

Funding

Postgraduate Scientific Research and Innovation Project, Central South University of Forestry and Technology (2025CX01110).

Declaration of competing interest

The authors declare that they have no conflicts of interest to disclose. All authors have approved the final version of the manuscript for submission.

Handling Editor: Professor Alejandro G.Marangoni