Phytoene increases lifespan, reduces oxidative stress and amyloid toxicity

By Dr. Liji Thomas, MDReviewed by Lily Ramsey, LLMSep 30 2024

New study reveals how microalgae extracts and phytoene combat aging, protect against Alzheimer’s toxicity, and extend lifespan.

Study: Phytoene and Phytoene-Rich Microalgae Extracts Extend Lifespan in C. elegans and Protect against Amyloid-β Toxicity in an Alzheimer’s Disease Model. Image Credit: Nguyen Anh Mai/Shutterstock.com

Antioxidants play a vital role in promoting health. A recent study published in Antioxidants highlights the protective benefits of microalgae extract and phytoene, showing they reduce oxidative stress, combat beta-amyloid toxicity, and extend lifespan in a worm model.

About carotenoids

Carotenoids are important compounds found in many plant and animal foods. They give bright colors to many fruits and vegetables, and they are also present in egg yolk, dairy, and some seafood. Another rich carotenoid source is the microalgae.

Carotenoids are metabolized to apocarotenoids, and both groups participate in many key plant physiological processes, including photosynthesis, plant communication, seed dispersal agents, and regulatory pathways.  

Carotenoids reduce the risk of many chronic disorders, including cancer, cardiovascular disease, cognitive impairment, metabolic disorders, and diseases of the skeletal system, skin, and eye. They maintain glowing skin by contributing to skin color and health as well.

This has led to the rollout of carotenoid-containing products of all kinds, including nutraceuticals and supplements, herbal foods, cosmeceuticals, and functional foods.

Microalgae

Microalgae are responsible for half the total global CO2 fixation. Besides carotenoids, microalgae are a rich source of other bioactives, polyunsaturated fatty acids (PUFAs), and essential amino acids.

Microalgae are a potentially sustainable source of healthful nutrition as they do not need farmland, grow 10-50 times faster than plants, and are easy to cultivate.

They adapt to a range of environments, including high and low temperatures, poor nutrient status, high salt content, and pollution. They do not need herbicide or pesticide application and thrive on much less water and nutrient supply.

Phytoene

Carotenoid synthesis in cells occurs by the conversion of geranylgeranyl pyrophosphate to phytoene via phytoene synthase. Phytoene is a colorless compound and is considered to lack bioactivity. As such, it has been ignored in most epidemiological studies on nutrition.

However, its daily intake is far above that of most other carotenoids. It is found in both plasma and urine at high levels, indicating significant bioavailability and bioaccumulation.

Phytoene is converted via lycopene to alpha- and beta-carotene. These are the sources of xanthophyll carotenoids, such as lutein and zeaxanthin. Zeaxanthin is an important precursor of other common microalgae-derived carotenoids, including violaxanthin and neoxanthin.

Study findings

In the current study, the researchers selected extracts from the microalgae Dunaliella bardawil and Chlorella sorokiniana. These species accumulate carotenoids, especially phytoene, and are widely used in commercial production.

The addition of norflurazone to growth media enriched their phytoene content to 45% and 47% for C. sorokiniana and D. bardawil extracts, respectively.

The investigators examined these extracts for bioactivity in comparison with pure phytoene in the model organism Cenorhabditis elegans.

Normal growth and development

Firstly, the researchers established that C. elegans continued to grow normally after treatment with phytoene or the extracts. Food availability was not affected. There was no inhibition of normal larval development to adulthood either.

Antioxidant potency

Next, they exposed the animal to juglone, a mitochondrial toxin that produces superoxides (negatively charged radicals). This was followed by treatment with pure phytoene and the extracts. This led to C. elegans survival by up to 53% compared to controls.

This demonstrated the ability of phytoene/microalgae extracts to enhance resistance to oxidative stress within a living system.

Protection against beta-amyloid toxicity

Thirdly, they used an engineered C. elegans model that produces human beta-amyloid (amyloid-β₄₂), causing proteins to clump and form amyloid plaques, characteristic of Alzheimer’s disease. In the worm, this protein is found in the body wall muscle, and its aggregation causes muscle dysfunction, resulting in paralysis.

Phytoene reduced paralysis from 62% in the controls to 37% and 40% in the animals treated with the D. bardawil and C. sorokiniana extracts, respectively, vs 43% with pure phytoene. This indicates that phytoene reduces protein toxicity due to amyloid-β₄₂ by 30% to 40%.

Increased lifespan

Fourthly, treatment with phytoene increased the lifespan by 10% and 18.6% (when treated with D. bardawil and C. sorokiniana extracts, respectively), compared to controls and by 15.5% with pure phytoene.

The findings thus indicate that phytoene treatment protects against oxidative stress and beta-amyloid toxicity, as well as extending the lifespan. Both microalgae-derived extracts provided similar levels of protection as pure phytoene.

This corroborates earlier research showing better health outcomes linked to higher carotenoid-rich food consumption like tomatoes. However, it also raises the question as to whether the conventional view that holds lycopene responsible is right. Alternatively, could lycopene be simply a marker for other phytochemicals that bring about this effect?

Phytoene may directly scavenge free radicals and promote the production of other scavengers, thus preventing oxidative damage. This explains why carotenoids are associated with a lower risk of cancer, diabetes, atherosclerosis, obesity, arthritis, and cognitive impairment.

An earlier study concluded that phytoene had a higher antioxidant capacity per double bond than expected vs. lycopene, though its fewer double bonds meant a lower overall antioxidant capacity.

Secondly, carotenoids not only scavenge reactive oxygen species but inhibit other pro-inflammatory response pathways while simultaneously activating antioxidant and detoxification enzyme cascades.

The net result is lower systemic inflammation and oxidative stress, with reduced prevalence and progression of chronic diseases like cancers and neurodegeneration.

Conclusions

“Our findings demonstrate for the first time in this model that phytoene has bioactivity and protects against aging, and suggest that phytoene-containing microalgae can be utilized to produce foods or supplements that promote healthy aging.”

The results also seem to indicate a biological role for phytoene even without conversion to other carotenoids, as shown by the similar outcomes obtained with the extracts as compared to pure phytoene. This may be the first time an increase in lifespan has been demonstrated with phytoene supplementation.