Ginseng
What is Panax Ginseng?
Panax ginseng (Asian ginseng) is a perennial herb whose root and other parts contain bioactive ginsenosides, polysaccharides, peptides and antioxidants (Su et al., 2023). Traditionally called the “king of herbs,” P. ginseng has been used in East Asia as an adaptogen and longevity tonic. Its active components (especially ginsenosides) exhibit multiple pro-health effects: antioxidant and anti-inflammatory actions, enhanced cellular repair and neuroprotection, and improvements in metabolism and organ function (Su et al., 2023). Modern research suggests that ginseng may slow aspects of systemic aging by acting on key longevity pathways. For example, ginseng extract has been reported to “slow down the aging process through DNA protection achieved by reduction in oxidative stress”(Su et al., 2023). This review details how Panax ginseng influences longevity-related mechanisms (e.g. stress-response, mitochondrial health, autophagy, inflammation, DNA repair, metabolism, cognition) and extends lifespan in model organisms, based on recent preclinical and clinical studies.
Antioxidant and stress-response pathways
Panax ginseng activates cellular antioxidant defenses to counter age-associated oxidative stress. Its ginsenosides and polysaccharides upregulate the Nrf2–Keap1 pathway, a master regulator of antioxidant gene expression (Su et al., 2023). Under stress, Nrf2 dissociates from its inhibitor Keap1 and translocates to the nucleus, promoting enzymes like glutathione S-transferase, superoxide dismutase and heme oxygenase-1 (Su et al., 2023). Ginseng compounds (e.g. ginsenoside Rg1) have been shown to activate PI3K/Akt signaling, leading to Nrf2 phosphorylation and increased antioxidant enzyme levels (Su et al., 2023). In animal studies, red ginseng extract raised brain and liver levels of endogenous antioxidants (GSH, SOD) and reduced markers of lipid peroxidation (Su et al., 2023 ; Lee et al., 2019). Ginseng also scavenges free radicals directly. In cultured cells and rodents, ginsenosides inhibit reactive oxygen species (ROS) generation and protect mitochondria from oxidative damage (Lee et al., 2019). By bolstering redox defenses, ginseng may prevent ROS-induced cellular senescence and tissue damage that accumulate with age (Ayu Silfia Budiasih, K., & Eka Handrean, G., 2025).
Mitochondrial function and energy regulation
Healthy mitochondria are central to longevity, and ginseng supports mitochondrial biogenesis and function via several pathways. Ginseng stimulates the NAD⁺-dependent sirtuins (especially SIRT1 and SIRT3), which deacetylate metabolic regulators to enhance mitochondrial health (Su et al., 2023). Major ginsenosides promote aerobic respiration and SIRT1-mediated mitochondrial biogenesis in heart and neuronal cells (Ziętara et al., 2023). SIRT1 activation improves oxidative metabolism and may mimic caloric restriction. Ginseng can also activate the energy sensor AMPK (adenosine monophosphate-activated protein kinase), although direct evidence in longevity models remains under study. Through SIRT1 and AMPK, ginseng enhances PGC-1α activity, improving mitochondrial turnover and ATP production.
Forkhead box O (FoxO) transcription factors are another nutrient-sensing longevity axis. Ginseng has been found to upregulate FoxO3 (the mammalian FOXO homolog) by inhibiting PI3K/Akt signaling (Su et al., 2023). FoxO3 in turn induces expression of antioxidant enzymes and mitochondrial quality-control genes. In rodent models, ginsenoside treatment preserved mitochondrial membrane potential and reduced neuronal apoptosis, effects consistent with FoxO3 activation (Su et al., 2023 ; Ziętara et al., 2023). Overall, ginseng shifts cells toward an energy-efficient, stress-resistant state by engaging SIRT and FoxO pathways.
Cellular Senescence and Proteostasis
Cellular senescence – permanent growth arrest – contributes to tissue aging via the senescence-associated secretory phenotype (SASP) and loss of repair capacity. Ginseng appears to delay senescence and promote proteostasis. In cultured cells, ginseng extracts reduced expression of p53/p21 and β-galactosidase, markers of senescence (Su et al., 2023). Mechanistically, ginsenosides can upregulate sirtuins (especially SIRT1 and SIRT6) that antagonize senescence-inducing pathways (Su et al., 2023). For example, the lignan syringaresinol (found in ginseng) activates SIRT1 and extended endothelial cell lifespan (Ayu Silfia Budiasih, K., & Eka Handrean, G., 2025). By maintaining NAD⁺ pools (via SIRT1/3/6 induction) and deacetylating p53/FoxO, ginseng reduces cell cycle arrest signals (Su et al., 2023).
Autophagy, the lysosomal clearance of damaged proteins and organelles, is vital for cellular health and longevity. Ginseng promotes autophagy in multiple models. Studies report that Korean red ginseng increases levels of autophagy markers (e.g. LC3-II) in aged tissues, enhancing clearance of dysfunctional components (Budiasih and Handrean, 2025; Du et al., 2025). In C. elegans, ginseng volatile oils extended lifespan by upregulating the autophagy receptor p62 (Su et al., 2023). Specific ginsenosides (e.g. Rg2) maintain mitochondrial function and delay neuronal aging by stimulating autophagy and degradation of p62 (Su et al., 2023). Inhibition of mTOR (a negative regulator of autophagy) is also observed: ginsenoside Rg3 downregulates PI3K/Akt and mTOR signaling, thereby inducing autophagy and reducing ROS (Su et al., 2023). In sum, ginseng enhances proteostasis by activating cellular recycling programs, counteracting the proteotoxic stress of aging (Budiasih and Handrean, 2025).
Inflammation and Immune Modulation
Chronic low-grade inflammation (“inflammaging”) accelerates aging and age-related diseases. Ginseng exhibits broad anti-inflammatory effects by targeting NF-κB and pro-inflammatory cytokines. The extract and active peptides of Panax ginseng have been shown to inhibit nuclear factor kappa B (NF-κB) activation, a key transcription factor for inflammatory genes (Su et al., 2023). For example, treatment with red ginseng extract or ginseng peptides lowered levels of IL-1β, IL-6 and TNF-α in multiple tissues of aged mice(Su et al., 2023). Ginsenoside Rc specifically suppresses the TBK1–IRF3 axis, thereby reducing TNF-α, IL-1β, and interferon production (Su et al., 2023). By dampening SASP factors, ginseng limits chronic inflammation and the accompanying ROS load.
Clinically, ginseng intake has been associated with modest anti-inflammatory benefits. Randomized trials indicate that ginseng supplementation can lower serum IL-6 and C-reactive protein in overweight or diabetic subjects, possibly by improving metabolic control. Moreover, ginseng polysaccharides have immunomodulatory effects – for example, enhancing macrophage phagocytosis and natural killer cell activity which may contribute to healthier aging (Ayu Silfia Budiasih, K., & Eka Handrean, G., 2025). Overall, ginseng’s anti-inflammatory actions (via NF-κB inhibition and cytokine reduction) relieve tissue stress and may protect against age-related inflammatory diseases.
DNA Repair and Genomic Stability
DNA damage accumulation is a fundamental hallmark of aging. Ginseng’s components promote DNA repair pathways and protect genomic integrity. Active ginsenosides enhance base excision and nucleotide excision repair by upregulating DNA glycosylases (e.g. NEIL1/3)(Su et al., 2023). In rodent studies, ginsenoside Rd increased neural NEIL1/3 expression and reduced DNA strand breaks (Su et al., 2023). Crucially, ginseng stimulates sirtuin-family DNA repair: SIRT6 binds and activates PARP1 to facilitate double-strand break repair (Su et al., 2023)(Su et al., 2023). Ginsenoside Rc increases SIRT6 deacetylase activity and thereby boosts PARP-mediated repair of oxidative lesions (Su et al., 2023)(Su et al., 2023). These effects accelerate resolution of DNA lesions, lowering pro-senescence signals.
Ginseng also appears to inhibit innate immune DNA-sensing pathways that drive inflammation. By blocking the cGAS–STING axis, ginseng ingredients prevent cytosolic DNA from triggering interferon responses (Su et al., 2023). This reduces chronic DNA-damage signaling and further protects cells from inflammatory DNA-sensing pathways. In sum, by enhancing repair enzymes (glycosylases, SIRTs, PARPs) and suppressing aberrant DNA-signaling, Panax ginseng helps maintain genomic stability during aging.
Metabolic and Endocrine Regulation
Aging is often accompanied by insulin resistance and metabolic dysregulation. Panax ginseng exerts beneficial metabolic effects that may support longevity. Clinical trials and meta-analyses show that ginseng modestly improves glycemic control. For example, a meta-analysis of 16 trials found that ginseng supplementation significantly lowered fasting plasma glucose (mean difference ~0.31 mmol/L) in people with or without diabetes (Shishtar et al., 2014). Some studies also report modest reductions in HbA1c and improved insulin sensitivity with long-term ginseng use (Shishtar et al., 2014). These effects likely arise from ginseng’s ability to activate AMPK and enhance insulin signaling in muscle and liver, as well as anti-inflammatory actions that improve metabolic homeostasis (Shishtar et al., 2014).
Ginseng also favorably influences lipid metabolism: supplementation tends to lower triglycerides, total and LDL-cholesterol in humans, though data are more variable. In animals, ginsenosides inhibit key enzymes of lipogenesis and promote fatty acid oxidation. By improving glucose and lipid profiles, ginseng may reduce metabolic stress on organs (Ayu Silfia Budiasih, K., & Eka Handrean, G., 2025) Moreover, ginseng can attenuate age-related adiposity and nonalcoholic fatty liver pathology in rodents via SIRT1/AMPK-mediated pathways. Collectively, these metabolic improvements can mitigate insulin/IGF-1 dysregulation, a known driver of aging aligning with the view that ginseng acts as a dietary-restriction mimetic (Shishtar et al., 2014).
Neurocognitive and organ-specific benefits
Panax ginseng exerts neuroprotective actions relevant to healthy brain aging. Ginsenosides penetrate the brain and influence multiple pathways: they enhance cholinergic neurotransmission, promote synaptic plasticity, and reduce neuroinflammation (Lho et al., 2018 ; Lho et al., 2018). In vitro and animal models of neurodegeneration, ginsenosides (e.g. Rb1, Rg1) inhibit Aβ aggregation and tau hyperphosphorylation, while upregulating neurotrophic factors. In human studies, long-term ginseng use is linked to better cognitive performance in the elderly (Lho et al., 2018). For instance, a Korean cohort study found that ≥ 5 years of ginseng intake was associated with higher cognitive test scores compared to nonusers. Controlled trials in Alzheimer’s patients suggest modest cognitive improvements with red ginseng, though results are mixed (Lho et al., 2018). Mechanistically, these cognitive benefits may derive from reduced neural oxidative stress, enhanced neuronal autophagy and synaptogenesis, and neurovascular protection by ginseng.
Aside from the brain, ginseng supports other organs’ resilience. In rodents, Panax ginseng promotes skin collagen synthesis and wound healing by activating growth factors and stimulating fibroblast proliferation. It also preserves muscle function by countering oxidative damage and by modulating myocyte IGF signaling, potentially slowing sarcopenia. In cardiovascular models, ginsenosides improve endothelial function via SIRT1 activation and eNOS modulation, protecting against age-related vascular stiffness. Thus, while not all organ-specific effects are fully mapped, available evidence indicates that ginseng helps maintain homeostasis in diverse tissues through its systemic antioxidant and metabolic actions (Ayu Silfia Budiasih, K., & Eka Handrean, G., 2025).
Longevity and lifespan studies in model organisms
Multiple preclinical studies indicate that Panax ginseng and its components can extend lifespan in invertebrate and vertebrate models. In the nematode C. elegans, supplementation with ginsenosides or ginseng peptides increased median lifespan by ~5-20% (Lee et al., 2019). For example, total ginseng saponins (300 μg/mL) extended worm lifespan and improved stress resistance; ginsenoside Rc was identified as a key active molecule (Lee et al., 2019). The longevity effect in worms depended on DAF-16/FoxO and SKN-1/Nrf2 pathways. Similarly, fermented ginseng extracts delayed aging markers in C. elegans via activating sir-2.1 and autophagy.
In fruit flies, Korean red ginseng (KRG) significantly prolonged lifespan on a full diet, primarily through nutrient-sensing pathways. A study found that KRG’s pro-longevity effect was abrogated in dSir2 (SIRT1) and insulin-like signaling mutants (Lee et al., 2019). In essence, ginseng mimicked dietary restriction by activating fly Sir2 and downregulating insulin/IGF-1 signaling, without reducing feeding or fertility (Lee et al., 2019). Likewise, It was reported life-extension in worms by purified ginsenosides. These cross-species results suggest ginseng’s anti-aging effects are evolutionarily conserved. However, mammalian longevity trials are limited. A 1979 study in mice reported no lifespan change with ginseng (Bittles et al., 1979), indicating that solid evidence in mammals is still lacking.
Conclusion
Panax ginseng engages a network of molecular targets known to influence aging. By activating antioxidant (Nrf2, FoxO3), sirtuin (SIRT1/3/6), and energy-sensing (AMPK) pathways, ginseng enhances mitochondrial function and reduces oxidative damage (Su et al., 2023 ; Ziętara et al., 2023). It suppresses chronic inflammation via NF-κB inhibition and cytokine reduction, and promotes proteostasis through autophagy and DNA repair (PARP/SIRT6) (Su et al., 2023). Together, the evidence supports a systemic anti-aging potential for Panax ginseng, warranting further clinical trials to define its long-term efficacy and optimal use.