American Study Finds That the Herb Centella Asiatica Promotes Healthy Aging by Inducing Distinct DNA Methylation Changes

Medical News: A recent study conducted by researchers from the Oregon Health & Science University (OHSU), including the BENFRA Botanical Dietary Supplements Research Center and the Knight Cardiovascular Institute, has revealed groundbreaking insights into the potential of Centella asiatica, an ancient herbal remedy, in promoting healthy aging. The researchers investigated how a water extract of Centella asiatica (CAW) influences DNA methylation - a vital epigenetic mechanism - in aged mice. This work may lay the groundwork for innovative approaches to mitigating age-related health challenges, offering a potential therapeutic pathway for enhancing longevity.


American Study Finds That the Herb Centella Asiatica Promotes Healthy Aging by Inducing
Distinct DNA Methylation Changes

Exploring the Science Behind Aging
Aging is a complex process influenced by various biological factors, including epigenetic modifications that alter gene expression without changing the DNA sequence itself. One such modification, DNA methylation, is increasingly recognized as a key biomarker of aging. With the global population aging rapidly, understanding and intervening in these processes has become a critical focus for researchers worldwide. This Medical News report delves into how Centella asiatica - a plant long revered in traditional Ayurvedic medicine for its neuroprotective and cognitive-enhancing properties - might impact aging processes at the molecular level.
 
The study’s authors aimed to uncover epigenetic changes induced by CAW in peripheral blood, which could serve as a minimally invasive biomarker for tracking its effects. Male and female mice, aged 18 months (equivalent to about 60 human years), were treated with CAW for five weeks. Using reduced representation bisulfite sequencing (RRBS), the team identified genome-wide DNA methylation changes, providing detailed insights into the herb’s biological impact.
 
Significant Gender-Based Differences
One of the most intriguing findings was the pronounced difference between male and female mice in their response to CAW. Males exhibited a significantly higher number of differentially methylated regions (DMRs) - nearly ten times more than females. This gender-based divergence highlights the nuanced nature of epigenetic responses and suggests that future therapeutic strategies involving Centella asiatica may need to be tailored by sex.
 
In male mice, most DMRs were hypomethylated, particularly in genes related to antioxidant pathways, mitochondrial function, and energy homeostasis.
 
Hypomethylation is often associated with increased gene expression, which could explain the herb’s reported ability to enhance cognitive function and reduce oxidative stress. These changes align with previous studies demonstrating Centella asiatica’s role in improving memory and executive function while alleviating anxiety.
 
Conversely, in female mice, the study identified hypermethylation in pro-inflamm atory genes and hypomethylation in anti-inflammatory genes, such as Il10, an anti-inflammatory cytokine. This dual regulation suggests that CAW might help balance inflammatory responses, a critical factor in healthy aging and disease prevention.
 
Pathways Enriched by CAW Treatment
The researchers identified several biological pathways influenced by CAW treatment, shedding light on the herb’s mechanisms of action:
 
-Oxidative Stress Response: In males, genes involved in the antioxidant response - such as those regulating glutathione metabolism - were hypomethylated. This finding reinforces the herb’s ability to bolster the body’s defenses against oxidative stress, a key contributor to aging.
 
-Energy and Mitochondrial Homeostasis: The study revealed hypomethylation in genes tied to mitochondrial function and energy regulation, which could underlie Centella asiatica’s reported effects on boosting cellular energy and improving metabolic health.
 
-Inflammatory Regulation: In females, pathways associated with inflammation showed significant changes, with hypermethylation in genes promoting inflammation and hypomethylation in those reducing it. This dual action may contribute to the herb’s anti-inflammatory properties observed in previous research.
 
-Calcium Signaling and Circadian Rhythm: Both males and females exhibited changes in genes regulating calcium homeostasis and circadian rhythm, processes essential for maintaining cellular health and overall well-being.
 
Transcription Factors and Gene Regulation
The study also examined transcription factor binding motifs within the identified DMRs, revealing sex-specific differences. In males, binding motifs for Kruppel-like factors (KLFs) were enriched. These transcription factors are involved in genomic integrity, cellular reprogramming, and systemic inflammation - all critical processes in aging. Notably, KLF14 and KLF3, which were highlighted in the study, have been previously linked to longevity and cognitive resilience.
 
In females, transcription factors from the ETS and IRF families were predominant. These are known to regulate immune responses and inflammatory pathways, which play significant roles in neurodegenerative diseases and age-related health decline. The enrichment of these motifs underscores the herb’s potential to modulate key regulatory networks involved in aging.
 
Implications for Future Research and Applications
The findings suggest that CAW induces distinct DNA methylation changes reflective of its broader biological effects, such as enhancing antioxidant defenses, modulating inflammation, and supporting metabolic health.
 
Importantly, these changes were observed in peripheral blood, suggesting that blood-based biomarkers could be used to track the herb’s effects in clinical settings. This approach could offer a practical and non-invasive way to monitor therapeutic outcomes in future human studies.
 
While these results are promising, more work is needed to establish a direct link between the observed methylation patterns in blood and similar changes in brain tissue. Such studies would provide critical validation for using peripheral blood as a surrogate marker for brain health, a key step in developing Centella asiatica as a therapeutic agent.
 
Conclusions
This study provides compelling evidence that Centella asiatica can influence epigenetic regulation in ways that align with its known health benefits. By modulating DNA methylation patterns, the herb appears to enhance pathways involved in antioxidant defenses, mitochondrial health, and inflammatory balance. These findings add to a growing body of research supporting the potential of Centella asiatica as a natural intervention for promoting healthy aging.
 
As the global population continues to age, the search for effective strategies to mitigate age-related decline has never been more critical. This research not only highlights the promise of Centella asiatica but also underscores the importance of considering gender-specific responses in therapeutic development. Future studies should aim to explore the long-term effects of CAW and its potential applications in human health.
 
The study findings were published in the peer-reviewed journal: Biology.
https://www.mdpi.com/2079-7737/14/1/52
 
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