Wormwood Whips Up Fat Storage to Increase Roundworm Lifespan
Aging and longevity are intimately linked to fat, as fat tissue seems to be a pivotal organ in the aging process and in the determination of lifespan. What remains unclear is how much fat is too much or too little. On the one hand, too much fat can lead to medical conditions that significantly shorten lifespan. On the other, too little fat can lead to frailty. Therefore, hitting the fat tissue sweet spot appears to be a trait often seen in centenarians.
Researchers from Louisiana State University show that a botanical extract that promotes fat storage and metabolic resiliency in mice also extends the lifespan of the nematode C. elegans by up to 40%. Published in The Journals of Gerontology, lead author Bhaswati Ghosh and colleagues show that a type of wormwood (Artemisia scoparia) can modify fat regulation, adding to growing evidence indicating that elevated fat can support healthy aging and longevity in some circumstances. Importantly, animals treated with this natural product are not only long-lived but also show improved stress resistance in late adulthood, suggesting that this fat-promoting intervention may enhance some aspects of physiological health in older age.
"Usually people think of fat as 'bad,' but in these cases, it seems good and actually pro-longevity," said Adam Bohnert, senior author and Assistant Professor at the LSU Department of Biological Sciences."Artemisia scoparia could have some exciting potential as a dietary supplement."
Fighting Fate With Fat
The majority of animal lifespan processes converge on metabolism. In the biology of aging, fat regulation, in particular, plays a complicated function that is very dependent on the context. Increased intake of various dietary fats, particularly saturated fats (such as butter), can contribute to age-related metabolic diseases. On the other hand, fat molecules, scientifically known as fatty acids, are essential components and regulators of cellular design, homeostasis, and signaling in biological systems.
As a result, not all fat is bad. Unsaturated fat-rich diets can improve metabolic health and lifespan in animal models, as have techniques that stimulate the manufacture of unsaturated fatty acids or inhibit their breakdown. While fat has become a prominent player in longevity regulation, tweaking relevant signaling pathways remains somewhat mysterious. Finding therapies that increase the accumulation of good fats might pave the path for new anti-aging medicines.
Au Naturale Adipose Augmentation
Natural products that modify core metabolic parameters, including fat content, may provide entry points to extend animal lifespan and promote healthy aging. Natural medicines produced from plants have a long and good track record of treating metabolic diseases. In animals, some varieties of the herbaceous plant Artemisia have properties that affect the regulation of sugar sensing in the blood, which is key to metabolism. Artemisia scoparia, which triggers fat-cell maturation in mice and has been claimed to increase insulin sensitivity by boosting fat storage, is a particularly fascinating and therapeutically promising example. This form of wormwood's favorable effects on fat storage and metabolic health implies that it may also aid in healthy aging. However, it is unknown if Artemisia scoparia can affect fat control in order to promote healthy aging and longevity.
Artemisia scoparia Supports Lifespan Extension in Roundworms
In this study, Ghosh and colleagues assessed the effects of this wormwood variety on lifespan and fat regulation using the roundworm C. elegans as a model organism. "The reason this study made so much sense to do in worms is because worms live for only about three weeks, so in a month or two, we had definite results," said Bhaswati Ghosh, an LSU student. "Also, the simple fact that an organism is short, fat, and slow-moving does not necessarily qualify it as in poor health. These [characteristics] must be considered in the full context of other parameters, including lifespan."
The LSU research team found that Artemisia scoparia treatment produced fatty animals that were long-lived. Remarkably, the lifespan extension with Artemisia scoparia supplementation was around 40% when initiated on the first day of adulthood. Additionally, significant lifespan extension and resiliency to multiple stressors were achieved when Ghosh and colleagues applied the botanical extract at later ages. This raised the exciting possibility that this plant-derived compound may provide an entry point to counter age-related disorders if given to older individuals.
Notably, this lifespan extension and resiliency depends significantly on the effects of Artemisia scoparia on fat. When treated with the wormwood variety, these treated worms exhibited heightened levels of unsaturated fat. And when Ghosh and colleagues inhibited fat-synthesizing enzymes called desaturases, it prevented the fat accumulation and lifespan extension promoted by this botanical extract.
"Until recently, it wasn't really known how aging could be modified through diet or how core metabolic signaling pathways influence longevity," Bohnert said. "What we've been able to show is that a natural extract can come in and influence these pathways in much the same way a genetic mutation would. Importantly, it gives us a therapeutic standpoint," Bohnert said. "We know age is the primary risk factor for many [medical conditions], but if you think of aging as a treatable disease, you can actually treat many diseases at once."
A Cacophony of Catchy Compounds
When compared to existing anti-aging medicines that have proceeded to trials in mammals, Artemisia scoparia has extraordinary impacts on roundworm longevity. Metformin, a botanically derived medication that modulates glucose metabolism, and rapamycin, a modulator of a nutrient-sensing pathway called mTOR, both enhance the longevity of C. elegans by 15-30%. Despite their promise, many medications have inevitable adverse effects, indicating the need for suitable alternatives. Importantly, our data show that the botanical extract is just as good as, if not better than, metformin and rapamycin in extending C. elegans longevity, as well as other lifespan-promoting plant extracts.
While Artemisia scoparia is presently unavailable commercially, this description of its pro-longevity properties, as well as previous studies suggesting its beneficial impacts on metabolic health, warrant further research and commercialization of this botanical extract as a pro-health dietary supplement.
Several bioactive chemicals from Artemisia scoparia have recently been found, including chlorogenic acid, which has been demonstrated to extend roundworm lifetime, but to a smaller amount than the botanical extract overall. While chlorogenic acid appears to have some lifespan-extending properties, it is inadequate to stimulate fat accumulation in animals. This suggests that other undiscovered chemicals may function in tandem with chlorogenic acid and other components in Artemisia scoparia-treated C. elegans to boost fat and longevity. It will be fascinating to see if this wormwood variety or its bioactive components may promote lifespan and good aging in animals in the future.
Ghosh B, Guidry HJ, Johnston M, Bohnert KA. A fat-promoting botanical extract from Artemisia scoparia exerts geroprotective effects on C. elegans lifespan and stress resistance. J Gerontol A Biol Sci Med Sci. 2022;glac040. doi:10.1093/gerona/glac040