Ashwagandha's many potential benefits for healthy aging

A central feature of cellular aging is the progressive failure of proteostasis, the complex network of pathways that regulate the synthesis, folding, and degradation of proteins. With age, this quality control system becomes less efficient, leading to the accumulation of misfolded, aggregated, and toxic proteins (Labbadia and Morimoto 2015). This proteotoxic stress is a key pathological feature of many age-related neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Ashwagandha has been shown to directly bolster cellular proteostasis. Its bioactive compounds, particularly withanone, can activate heat-shock proteins (HSPs), which act as molecular chaperones to refold damaged proteins and prevent aggregation (Mikulska et al. 2023). Furthermore, they can enhance the function of the ubiquitin–proteasome system, the cell's primary machinery for degrading and clearing out toxic proteins, thereby alleviating the burden of cellular damage that accumulates over time (Ghosh et al. 2017).

Mitochondrial dysfunction is another central pillar of aging. As mitochondria, the cell's powerhouses decline in function, cellular energy production falters, and the output of damaging reactive oxygen species (ROS) increases. This creates a vicious cycle of oxidative stress that damages cellular components, including DNA, lipids, and proteins. Ashwagandha effectively mitigates this age-related mitochondrial decay by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant defense pathway (Basudkar et al. 2024). Nrf2 is a master regulator of cellular redox balance, and its activation by Ashwagandha's withanolides triggers the expression of a broad array of protective antioxidant and detoxification enzymes. This action shields mitochondria from oxidative damage, preserves their integrity, and supports robust cellular energy production, thus countering one of the primary drivers of cellular aging (Saleem et al. 2020).

The aging process is intricately controlled by a set of highly conserved nutrient-sensing pathways that coordinate metabolism with cell growth and repair. Key among these is AMP-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1), which are recognized as central regulators of longevity (Wiciński et al. 2024). Interventions known to extend healthspan, such as caloric restriction, exert their benefits largely by activating these pathways. Emerging evidence indicates that Ashwagandha's influence extends to these critical regulatory hubs. It has been shown to modulate key longevity regulators like AMPK and SIRT1, which in turn orchestrates a pro-longevity program of enhanced cellular repair, improved stress resistance, and reduced inflammation. By engaging these pathways, Ashwagandha can mimic some of the profound cellular benefits of caloric restriction without the need for dietary limitation, positioning it as a potential caloric restriction mimetic (Saha et al. 2024).

By simultaneously addressing proteotoxic stress, metabolic decline, and oxidative damage at a molecular level, Ashwagandha presents a uniquely comprehensive strategy for promoting healthspan. These foundational mechanisms provide a clear biological basis for the wide-ranging physiological, cognitive, and neuroprotective benefits observed in clinical settings, which will be detailed in the subsequent sections.

The aging process is characterized by a gradual decline in physiological function, including reduced muscle mass and strength (sarcopenia), diminished cardiorespiratory endurance, hormonal imbalances, and poor sleep quality. Research indicates that Ashwagandha can significantly mitigate many of these age-related declines.

Preclinical studies in model organisms provided the foundational evidence for Ashwagandha's pro-longevity effects. At a fundamental cellular level, a key marker of aging is the shortening of telomeres, the protective caps on our chromosomes. An extract of Ashwagandha root has been shown in vitro to significantly boost the activity of telomerase, the enzyme responsible for maintaining telomere length (Jacczak et al. 2021). In one study using human cell lines, the extract increased telomerase activity by approximately 45%, suggesting a direct mechanism for promoting cellular longevity (Raguraman et al. 2016). In Caenorhabditis elegans, an extract of Ashwagandha root was shown to extend mean lifespan by approximately 20%, while also improving late life healthspan by enhancing pharyngeal pumping and locomotor activity (Thakkar et al. 2025). Further research in Drosophila melanogaster (fruit fly) demonstrated that withaferin A, a key withanolide, protects against age-related physiological decline, improves stress resistance, and extends lifespan, establishing its geroprotective potential (Koval et al. 2021).

Building on this, human trials have demonstrated tangible benefits. Maintaining muscle mass is critical. A landmark trial found that Ashwagandha (600 mg/day) in adults undergoing resistance training resulted in a significantly greater increase in muscle strength (e.g., a ~ 46 kg increase in bench press 1-rep max vs. ~ 26 kg for placebo) and muscle size (e.g., an 8.6 cm² increase in arm muscle area vs. 5.3 cm² for placebo) (Wankhede et al. 2015). A similar study confirmed these anabolic effects, showing improvements in both upper and lower body strength and a favourable increase in lean body mass (Bonilla et al. 2021). This is complemented by evidence showing a significant reduction in exercise-induced muscle damage, as measured by lower serum creatine kinase levels, suggesting faster recovery (Verma et al. 2025).

Cardiorespiratory fitness (VO2 max) is a strong predictor of longevity. A trial with healthy athletic adults demonstrated that 12 weeks of supplementation (300 mg twice daily) significantly enhanced VO2 max by 13.6% compared to 9.7% in the placebo group and improved self-reported quality of life scores on the WHOQOL-BREF scale (Strasser and Burtscher 2018). Another study corroborated these findings in elite cyclists, who showed a 12% improvement in time-to-exhaustion on a treadmill test after eight weeks (Shenoy et al. 2012).

The herb's benefits also extend to skin health, a visible marker of aging. In a randomized, double-blind, placebo-controlled clinical trial on healthy adults with photoaged facial skin, the topical application of a lotion containing 8% standardized Ashwagandha root extract for 60 days led to significant improvements. Compared to the placebo, the Ashwagandha group showed greater improvements in skin hydration (20.66% vs 9.5%), elasticity (16.34% vs 3.73%), and a reduction in trans-epidermal water loss. Physician assessments also noted significant reductions in wrinkles and pore size (Narra et al. 2023).

Hormonal balance is also crucial. A systematic review and meta-analysis concluded that Ashwagandha supplementation significantly increased testosterone levels, with a pooled effect size showing an average increase of 145.7 ng/dL in male participants (Lopresti et al. 2019). Specific trials confirmed its efficacy in improving semen parameters (sperm concentration, motility) in infertile men (Mutha et al. 2025) and boosting testosterone by 14.7% and the anti-aging hormone DHEA-S by 18% in overweight, aging males (Lopresti et al. 2019). In perimenopausal women, an 8-week RCT showed that Ashwagandha significantly reduced menopausal symptoms, as measured by the Menopause Rating Scale (MRS), and improved hormonal balance (Gopal et al. 2021). A clinical trial involving healthy women also found significant benefits for female sexual well-being. Participants showed statistically significant improvements across multiple key domains of the Female Sexual Function Index (FSFI), covering both subjective experience and physiological response (Ajgaonkar et al. 2022).

Finally, sleep quality and stress management are foundational to healthy aging. A comprehensive review found Ashwagandha has a significant beneficial effect on overall sleep (Haber et al. 2024). A trial in healthy older adults (65–80 years) showed improved sleep quality, a significant increase in mental alertness upon waking, and better quality of life scores (Kelgane et al. 2020). Its adaptogenic effects are highlighted by its ability to significantly reduce levels of stress hormone cortisol. A key study on chronically stressed adults reported a 27.9% reduction in serum cortisol levels after 60 days of supplementation, which correlated with dramatic reductions in scores on perceived stress scales (Chandrasekhar et al. 2012). This cortisol-modulating effect is a cornerstone of its anti-aging action, as chronically elevated cortisol accelerates cellular aging (Gómez Afonso et al. 2023).

Cognitive decline is one of the most feared aspects of aging. Ashwagandha has emerged as a promising nootropic and neuroprotective agent, with a growing body of clinical evidence supporting its efficacy in ameliorating these changes.

A pivotal 8-week RCT in adults with mild cognitive impairment (MCI) found that Ashwagandha root extract (300 mg twice daily) led to significant improvements in both immediate and general memory, as assessed by the Wechsler Memory Scale-III. Sub-scales such as logical memory and verbal paired associates showed marked improvement. Furthermore, participants demonstrated enhanced executive function, sustained attention, and a faster information-processing speed compared to the placebo group (Choudhary et al. 2017). A more recent 12-week trial in adults with MCI further confirmed these findings, showing significant enhancements in working memory and general memory with a standardized extract (Gopukumar et al. 2021). Another RCT highlighted its ability to improve recall memory and reduce error rates in cognitive tasks, underscoring its potential for those with memory complaints (Leonard et al. 2024).

The benefits extend to healthy populations. A trial in healthy individuals found that Ashwagandha improved reaction time and performance on various attention-based tasks, suggesting a role in maintaining peak cognitive performance (Puttaswamy et al. 2025). Its utility has also been explored in conditions with cognitive deficits, such as bipolar disorder, where an 8-week trial showed it improved auditory-verbal working memory, reaction time, and social cognition (Xing et al. 2022). A systematic review concluded that Ashwagandha intake could indeed improve cognitive function across various populations, including the elderly and those with MCI (Ng et al. 2020).

The mechanisms behind these cognitive benefits are multifaceted and are actively elucidated through preclinical research. In a mouse model of scopolamine-induced amnesia, Ashwagandha was shown to reverse memory deficits by inhibiting the enzyme acetylcholinesterase (AChE), thereby increasing acetylcholine levels in the brain, a mechanism like that of many dementia medications (Gautam et al. 2016). Other animal studies have shown that withanolides can promote the regeneration of neurites and the reconstruction of synapses, directly countering the age-related decline in synaptic plasticity (Kuboyama et al. 2005). In a mouse model of cerebral ischemia, Ashwagandha reversed neuronal impairment and cognitive deficits by restoring cerebral blood flow and reducing inflammation (Zhang et al. 1997). Furthermore, it enhances spatial memory by promoting neurogenesis and increasing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, the brain's primary memory centre (Er et al. 2025). It also appears to protect against glutamate-induced excitotoxicity, a common pathway of neuronal damage in both acute injury and chronic disease (Kataria et al. 2012).

Inflammaging, the chronic, low-grade inflammation that accompanies aging, is a primary driver of most age-related diseases. Ashwagandha possesses potent anti-inflammatory and immunomodulatory properties that directly counter this insidious process.

Clinical studies provide direct evidence of its anti-inflammatory action. A foundational study in chronically stressed adults found that Ashwagandha supplementation significantly decreased C-reactive protein (CRP), a key biomarker of systemic inflammation, by over 30% (Guo and Rezaei 2024). A meta-analysis of multiple RCTs later confirmed that Ashwagandha consistently lowers CRP levels (Raut et al. 2024). Another systematic review highlighted its ability to also reduce levels of other pro-inflammatory cytokines like interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) (Arshad et al. 2025). This is further supported by research showing its ability to modulate oxidative stress, significantly reducing the lipid peroxidation marker malondialdehyde (MDA) while boosting levels of endogenous antioxidants like superoxide dismutase (SOD) (Paul et al. 2021).

Ashwagandha demonstrates efficacy in managing specific inflammatory conditions. In an RCT on patients with knee joint pain, Ashwagandha significantly reduced pain scores on the Visual Analog Scale (VAS) and improved physical function (Ramakanth et al. 2016). Its benefits in rheumatoid arthritis have also been documented, where it helped reduce disease activity scores. Preclinical research using animal models of arthritis has shown it can reduce pro-inflammatory cytokines, suppress cartilage degradation by inhibiting matrix metalloproteinases, and alleviate pain (Samy et al. 2025). Mechanistically, its active compounds, particularly withaferin A, are known to inhibit the master inflammatory transcription factor NF-κB by blocking the activation of its upstream kinase, IKKβ (Heyninck et al. 2014).

In addition to curbing inflammation, Ashwagandha modulates the immune system to counter age-related immune senescence. A landmark research study in healthy adults demonstrated that supplementation significantly increased the activity of Natural Killer (NK) cells, the body's first line of defence against viral infections and tumours. The study also noted an increase in the activation of T-cell subsets, indicating a broad-spectrum enhancement of adaptive and innate immunity (Alanazi and Elfaki 2023). A more recent trial confirmed these effects, showing a significant increase in CD4 + T helper cells, CD8 + T cytotoxic cells, and NK cells after 30 days of supplementation, bolstering the body's surveillance capabilities (Mikolai et al. 2009). This dual ability to suppress chronic inflammation while enhancing protective immune responses makes it a powerful tool for managing the immunological challenges of aging (Della Porta et al. 2023).

The COVID-19 pandemic introduced novel health challenges, including the management of post-viral syndromes like "long COVID." Long COVID is defined as "an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems". Beyond multiple diagnosable conditions, long COVID symptoms may include shortness of breath, cough, persistent fatigue, post exertional malaise, difficulty concentrating, memory changes, recurring headache, lightheadedness, fast heart rate, sleep disturbance, problems with taste or smell, bloating, constipation, and diarrhea. The established properties of Ashwagandha led researchers to investigate its potential in the contexts of COVID-19 and long COVID.

Initial research on COVID-19 and Ashwagandha focused on computational and in-vitro studies. Molecular docking simulations suggested that withanone, a key compound, could inhibit the SARS-CoV-2 main protease, an enzyme essential for viral replication, by binding to its active site (Kandagalla et al. 2022). These simulations also proposed that Ashwagandha's components could interfere with the virus's ability to bind to host cell receptors like ACE2, potentially blocking viral entry (Balkrishna et al. 2021). Another in-silico study proposed that Ashwagandha compounds could modulate the inflammatory cytokine storm by inhibiting key signalling pathways like JAK/STAT, which is often dysregulated in severe COVID-19 (Singh et al. 2022).

These promising preclinical findings paved the way for human trials. An early pilot study in patients with mild COVID-19 suggested Ashwagandha as an adjunct therapy could contribute to faster recovery and resolution of symptoms, likely by mitigating the hyper-inflammatory response (Singh et al. 2023). A larger randomized controlled trial investigated it as a prophylactic and found that while it did not significantly reduce the incidence of infection, it was associated with a higher self-reported quality of life during the pandemic period and showed a trend towards promoting faster recovery in those who did get infected (Kulkarni-Munshi et al. 2025).

Regarding long COVID, a large-scale, randomized, placebo-controlled clinical trial, the "APRIL Trial," was initiated in the UK to formally assess the efficacy of Ashwagandha in promoting recovery (Mallinson et al. 2025). While results from this major trial are pending, the investigation represents a modern application of its traditional use as a restorative tonic. Providing early clinical support, a published case report has already documented significant improvements in fatigue, sleep, and cognitive symptoms in a long COVID patient after supplementation with Ashwagandha, suggesting its therapeutic potential for this complex post-viral condition (Smith et al. 2023).

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's, are among the most devastating age-related conditions. Ashwagandha has shown remarkable potential in preclinical models of these diseases, suggesting it could play a role in slowing or halting their progression by targeting multiple pathological pathways.

In Alzheimer's disease (AD), a groundbreaking study in a mouse model found that an Ashwagandha root extract induced a liver protein (lipoprotein receptor-related protein 1, or LRP1) that facilitated the clearance of amyloid-beta (Aβ) from the brain. This led to a significant reduction in Aβ plaque burden and a reversal of associated behavioural deficits (Sehgal et al. 2012). Another key study showed withanolide derivatives could promote the reconstruction of both pre- and post-synaptic terminals, directly countering the synaptic loss that underlies cognitive decline in AD (Kuboyama et al. 2005). Furthermore, Ashwagandha protects neurons from Aβ-induced toxicity by reducing oxidative stress, preserving mitochondrial function, and inhibiting apoptosis (Tancreda et al. 2025). It has also been shown to inhibit the enzyme acetylcholinesterase, a mechanism like some existing AD drugs (Idrees et al. 2023).

For Parkinson's disease (PD), which involves the loss of dopamine neurons, Ashwagandha has also shown promise. In a mouse model of PD, treatment with Ashwagandha extract was found to significantly improve motor function, reduce neuroinflammation by modulating microglial activation, and protect dopaminergic neurons from degeneration (RajaSankar et al. 2009). The mechanisms involve the upregulation of key antioxidant pathways like Nrf2, which boosts cellular defences (Kim et al. 2025), and protection against MPTP-induced neurotoxicity by restoring levels of dopamine and its metabolites in the striatum (RajaSankar et al. 2009).

The herb's neuroprotective effects extend to other conditions. In a mouse model of Huntington's disease, an inherited neurodegenerative disorder, Ashwagandha extract improved motor performance, reduced the size of toxic protein aggregates (striatal inclusion bodies), and extended survival (Mohd Sairazi and Sirajudeen 2020). In models of cerebral ischemia (stroke), it has protected brain tissue from damage and improved functional recovery by reducing inflammation and apoptosis in the ischemic penumbra (Raghavan and Shah 2015). Studies have also shown its potential in models of chemotherapy-induced cognitive impairment (chemo brain) and in mitigating neuronal damage following traumatic brain injury (Singh et al. 2024). A systematic review concluded that Ashwagandha holds significant therapeutic potential for a range of neurodegenerative diseases, though it emphasized the urgent need for well-designed human clinical trials to translate these robust preclinical findings into effective therapies (Sandhir and Sood 2017).

The extensive body of research synthesised here highlights Ashwagandha's remarkable potential as a multifaceted agent for promoting healthy aging. From enhancing physical strength and cognitive function to modulating the intricate pathways of inflammation and neurodegeneration, its traditional status as a Rasayana is strongly supported by modern scientific evidence. However, significant challenges remain in translating this promise into mainstream clinical practice which are discussed in the next sections.