The study, conducted at the Salk Institute for Biological Studies, examined how the NOVOS Core formulation interacts with cellular models of oxytosis/ferroptosis and inflammation, two biological processes commonly studied in aging research.
For a more technical version of this article, click here.
All NOVOS-related findings described in this article were generated in vitro using cellular models and are intended for research purposes only. These results do not establish effects in humans or relevance to health or disease outcomes.
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Introduction to Ferroptosis
Ferroptosis is a recently identified form of regulated cell death that has been associated with various pathological processes in basic and translational research, including cancer biology, neurodegenerative disease models such as Alzheimer’s and Parkinson’s, and ischemia-reperfusion injury, making it an active area of investigation in fundamental biology (Li et al., 2020; Xie et al., 2016; Stockwell et al., 2017).
(Note: In vitro findings described in this article reflect observations in cellular systems only. Such results are exploratory and do not establish effects in humans or relevance to health or disease outcomes. No claims are made regarding diagnosis, prevention, treatment, or mitigation of any disease. This content is provided for scientific and educational purposes only.)
Introduction to Oxytosis
Oxytosis, on the other hand, is a form of cell death first described over 30 years ago, primarily in nerve cells, that can also induce cell death.
Oxytosis and ferroptosis share several cellular features that are commonly studied in experimental models of neurodegeneration and brain aging.
NOVOS Core Oxytosis/Ferroptosis Study Approach and Results
Scientists utilized two mixtures based on the NOVOS Core formulation: a water-soluble mix and a non-water soluble mix prepared in dimethyl sulfoxide (DMSO), containing fisetin and pterostilbene. These mixtures were tested both separately and combined in assays to assess their protective effects against induced oxytosis/ferroptosis in HT22 mouse hippocampal neuronal cells and their anti-inflammatory activity in LPS-activated BV2 microglial cells. This dual approach was used to observe how the formulation influences cellular stress responses and inflammatory signaling pathways that are widely studied in aging-related research models.
The results from Table 1 demonstrate the efficacy of different mixtures of the NOVOS Core formulation in protecting HT22 mouse hippocampal neuronal cells against cell death induced by glutamate, erastin, and RSL3, which are agents known to initiate the oxytosis/ferroptosis pathway. This pathway is commonly examined in experimental research focused on cellular stress responses associated with aging.
The protection afforded by the mixtures is quantified as the effective concentration (EC50) required to protect 50% of the cells. The total mix of all NOVOS Core ingredients resulted in significantly enhanced protection across all tests. This marked improvement suggests a synergistic interaction between the combined ingredients within the NOVOS Core formulation, resulting in stronger effects on ferroptosis-related cellular markers than individual mixtures under the same laboratory conditions.
NOVOS Core Anti-Inflammatory Study Approach and Results
The results from Table 2 of the study reveal insightful findings regarding the anti-inflammatory activity of the NOVOS Core formulation in BV2 microglial cells treated with lipopolysaccharide (LPS). These outcomes provide insight into how the formulation influences inflammatory signaling in cellular systems commonly used to study aging-related stress responses.
The combined NOVOS Core mix as well as the non-water-soluble DMSO mix of Core’s ingredients both exhibited significant anti-inflammatory activity, as evidenced by their effective concentration (EC50) values of 3.2 μl per 10^5 and 2.4 μl per 10^5 cells, respectively
Commentary on the Study’s Results
Synergistic Reduction in Oxytosis/Ferroptosis
The study’s findings provide insight into how the NOVOS Core formulation influences cellular responses to experimentally induced stressors in neuronal cell models.
The complete NOVOS Core formulation (“total mix”), demonstrated remarkable protective effects against the induction of oxytosis/ferroptosis by glutamate, erastin, and RSL3. The total mix’s enhanced efficacy suggests a synergistic interaction between its components, surpassing the protective capabilities of the separate water-soluble and DMSO-soluble mixes of NOVOS ingredients. This synergy indicates that the formulation’s components work together more effectively than individually, a critical insight into the unique nature of NOVOS Core’s patent-pending combination of ingredients.
The finding aligns with previous research emphasizing the importance of multifactorial approaches in combating complex pathways like ferroptosis, where cellular iron homeostasis and lipid peroxidation play significant roles (Li et al., 2020; Xie et al., 2016).
Anti-inflammatory Activity of NOVOS Core
The formulation reduced nitric oxide (NO) production in LPS-stimulated microglial cells, a commonly used experimental model for studying inflammatory signaling pathways in laboratory settings. This finding is consistent with the growing body of literature that identifies neuroinflammation as a critical target in the prevention and treatment of diseases like Alzheimer’s and Parkinson’s (Mirzoeva et al., 1999; Ngo et al., 2012).
Low Doses Are Highly Effective
The substantial reduction in EC50 values with the combined NOVOS Core formula across all inducers—glutamate, erastin, and RSL3—highlights the formulation’s robust neuroprotective capacity at potentially low doses, demonstrating measurable effects at low concentrations within this experimental system.
Chronic inflammation is a hallmark of aging and is implicated in the progression of neurodegenerative diseases. The ability of the NOVOS Core formulation to reduce LPS-induced NO production in microglial cells highlights its relevance for further mechanistic research in cellular aging models. Targeting microglial activation and the subsequent inflammatory cascade can be crucial in developing strategies to mitigate the impact of aging on the brain and prevent or slow the progression of neurodegenerative diseases (Heneka et al., 2015). The results from the anti-inflammatory activity assay provide valuable insights into the components of the NOVOS Core formulation that are most effective in reducing neuroinflammation.
In summary, the results of this study not only affirm the NOVOS Core formulation’s cellular stress–response and inflammatory signaling effects but also emphasize the synergistic potential of combining water-soluble and lipid-soluble components. This multifaceted approach to neuroprotection and neuroinflammation mitigation stands out in the field of longevity research.
Contextualizing the Findings in Aging and Aging Research
This study conducted on NOVOS Core by the Salk Institute’s neuroscientist, Dr. Pamela Maher, provides mechanistic evidence of how the formulation interacts with cellular processes commonly studied in aging-related research.
Addressing the Complexity of Aging
Aging is a multifactorial process characterized by the gradual decline in physiological functions, including the brain’s ability to maintain homeostasis and respond to stress. The NOVOS Core formulation’s ability to protect against oxytosis/ferroptosis and reduce neuroinflammation touches on two pivotal aspects of aging at the cellular level: the accumulation of damage due to oxidative stress and the chronic inflammation often referred to as “inflammaging” (Franceschi and Campisi, 2014). By targeting these pathways, the NOVOS Core formulation may contribute to preserving neuronal integrity and function, potentially delaying the onset or progression of age-related cognitive decline.
Synergistic Approach to Neuroprotection
The study highlights the importance of a synergistic approach to neuroprotection, resonating with the complexity of aging-related cellular damage pathways. The enhanced efficacy of the complete NOVOS Core formulation suggests that a multi-targeted strategy may be more effective in countering the broad range of challenges faced by aging cells. This aligns with current trends in aging research, which advocate for interventions that can simultaneously address multiple aging hallmarks (Kennedy et al., 2014).
Implications for Neurodegenerative Disease
Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, are among the most daunting challenges of aging, significantly affecting quality of life. The demonstrated in vitro protective effects of the NOVOS Core formulation against cell death and inflammation provide a foundation for further basic research into how multi-ingredient formulations influence cellular stress and inflammatory pathways. (Cummings et al., 2016).
Conclusion
This NOVOS Core study represents a step forward in the quest to intervene in the aging process and its associated neurodegenerative conditions. By providing evidence of protection against oxidative stress-induced cell death and inflammation, this research contributes to a growing body of evidence supporting the unique multi-pathway cellular effects observed in this in vitro study. As aging research continues to evolve, studies such as this underscore the potential for innovative, synergistic formulations to address the complex challenges of aging, offering hope for healthier, more resilient aging populations.
