Researchers have tested several combinations of ingredients with anti-aging properties. Those combinations, including a 12-ingredient formulation created by NOVOS, helped to reduce DNA damage and oxidative stress in human skin cells in cultures [1].
Fighting multiple Hallmarks of Aging at once
Aging impacts multiple cellular processes, and these impacts can be assessed through biomarkers. The researchers of this paper used human skin cells (keratinocytes) as their targets for assessing the impact of the NOVOS supplement and six other formulations on DNA damage and oxidative stress markers. They believe that since skin is frequently exposed to DNA-damaging agents, such as UV light, it is the right choice for assessing these markers.
The tested supplement formulation created by NOVOS, a New York-based company, is a mix of 12 ingredients: pterostilbene, a resveratrol-related polyphenol derived from blueberries; glucosamine sulfate, a supplement used for osteoarthritis treatment; fisetin, a senotherapeutic; glycine, an amino acid; lithium aspartate, a mineral; calcium alpha-ketoglutarate, a small molecule present in the human body; magnesium malate, a natural substance found in apples; vitamin C, also known as ascorbic acid; L-theanine, an amino acid found primarily in green and black tea; hyaluronic acid; Rhodiola rosea root extract; ginger root extract; and a boost consisting of β-nicotinamide mononucleotide.
These nature-based ingredients, all of which have good safety profiles, were selected based on their anti-aging activity, documented role in counteracting multiple aging processes, or association with aging-related mechanisms. We have previously written about them and their selection process in more detail.
The authors explained that they tested combinations of different compounds because this approach could address multiple aging processes at once. A combination of compounds could also effectively reduce unwanted side effects that can appear when a single compound is used in high concentrations.
Reduction in DNA damage
Even beneficial ingredients can be toxic in excessive concentrations. Therefore, the researchers started their study by assessing the compounds’ highest safe concentrations to use. They followed up by testing the impact of supplement formulation on protecting cells from DNA damage, using tumor p53 binding protein 1 (53BP1) as a DNA damage marker.
The researchers treated 2D cell cultures with the six formulations and NOVOS. Following this treatment, they induced DNA damage with the genotoxic agent neocarzinostatin (NCS).
Data analysis revealed that treating cells with the six different formulations caused mild adverse effects on cells, as evidenced by higher numbers of DNA damage-related foci in some cells. NOVOS treatment did not cause that.
Cells pre-treated with NOVOS were less likely to have many of these foci after NCS administration, which suggests that NOVOS helps alleviate the DNA damage caused by NCS. However, it didn’t bring the damage down to the level of control cells that were not exposed to NCS.
The six different formulations also positively affected cells exposed to NCS. Those formulas “significantly prevented DNA damage, observed as reduced foci numbers, even with a stronger effect compared to the NOVOS’ original formulation itself.”
Based on this statistical analysis and the number of ingredients in each formulation, the researchers chose NOVOS, F1, F2, and F4 for the following experiments.
The first was a test of one more DNA damage marker, γ-H2AX, a marker that reflects double-strand breaks in the DNA. However, they performed it in the 3D skin cell cultures since 3D cultures better reflect the skin microenvironment and ”allow the formation of a cellular structure, like a tissue.” The results of this experiment suggested that all four of these formulations significantly reduced DNA damage compared to cells that were only exposed to NCS.
Notably, the concentration of NOVOS used in this experiment is lower than that of other formulations. Still, it can achieve similar effects in counteracting DNA damage as F1, F2, and F4. The authors suggest that this may be because of some synergistic effects between the NOVOS compounds.
Decreased oxidative stress
In the following test, the researchers aimed to assess the formulations’ ability to prevent oxidative damage to the cells. Intracellular reactive oxygen species (ROS) are difficult to measure. However, since many of them are converted to hydrogen peroxide, hydrogen peroxide can be used as a proxy for intracellular ROS level changes and oxidative stress.
The researchers performed this experiment using 2D and 3D cultures. Those cells were treated with different F1, F2, F4, and NOVOS formulation concentrations. Then, the researchers used the pro-oxidant medication to induce oxidative damage.
F1 and F4 formulations were able to significantly reduce intracellular hydrogen peroxide production following menadione treatment in 2D and 3D cell cultures. NOVOS was able to achieve this in 2D but not 3D culture.
Limitations
This study suggests that NOVOS, along with the F1, F2, and F4 combinations, are able to counteract some aging-related processes in skin cells.
While the researchers discussed the benefits of using a combination of compounds over a single compound, this research lacks an experiment that compares the combinations to single compounds. Such experiments would be very informative in testing whether the observed effects result from the combined effect of the multiple compounds or whether the observed effects come mainly from the action of a single compound and there is a negligible contribution from the remaining compounds, which would allow for simpler supplements. This is notable as the F1, F2, and F4 combinations with half the NOVOS compounds show similar effects as NOVOS in the experiments.
The authors also note that further investigation into specific molecular pathways involved in the observed processes is necessary.
One of the study authors is an employee of NOVOS Labs. However, in the Conflict of Interest, the authors note: ”The funder NOVOS Labs was not involved in the study design, collection, analysis, interpretation of data, of this article or the decision to submit it for publication.”
Disclosure: A portion of the profits and equity from NOVOS are being donated to nonprofits working in the longevity science space, which includes us here at Lifespan.io.
Our Vice President, Dr. Oliver Medvedik, is also a scientific consultant, putting him in good company with Dr. Joao Pedro Magalhaes, Dr. Pamela Maher, Dr. Avi Rosenbaum, and Dr. Matt Kaeberlein, names with whom regular readers may be familiar.
Literature
[1] Punzo, A., Perillo, M., Silla, A., Malaguti, M., Hrelia, S., Diogo Barardo, Cristiana Caliceti, & Lorenzini, A. (2024). Promising Effects of Novel Supplement Formulas in Preventing Skin Aging in 3D Human Keratinocytes. Nutrients, 16(16), 2770–2770.
