Betulinic acid increases lifespan and stress resistance via insulin/IGF-1 signaling pathway in Caenorhabditis elegans

Abstract

Numerous studies reported that betulinic acid (BA), a natural product extracted from birch bark, exhibited various beneficial effects in vitro. However, its pharmacological activities in aging are rarely understood. In this study, Caenorhabditis elegans was deployed as a whole animal model to investigate the impacts of BA on lifespan and stress resistance. Wild-type C. elegans were fed in the presence or absence of BA and tested for a series of phenotypes, including longevity, mobility, reproductive capacity, pharyngeal pumping, heat stress, and oxidative stress. BA at the optimal dose (50 μg/mL) extended the lifespan, improved the healthspan, and significantly evoked the increased oxidative stress resistance in C. elegans. Incorporating the genetic analysis with different types of longevity mutants, DAF-16, the downstream effector of the Insulin/IGF-1 receptor signaling, was revealed to mediate the protective effects of BA on lifespan and antioxidant activity. Together, these data showcased the potential of BA in promoting healthy aging, which shall facilitate its further development in the food and pharmaceutical industries.

Astaxanthin Induces Transcriptomic Responses Associated with Lifespan Extension in Caenorhabditis elegans

“…In this study, the higher concentrations of astaxanthin were less effective for increasing the lifespan of C. elegans . Similar dose-response effects on lifespan were found for other bioactive compounds [ 61 , 62 ]. It is well established that both nutrients and beneficial/toxic chemicals may produce opposite consequences for an organism depending on the doses.…”

Betulinic Acid Increases the Lifespan of Drosophila melanogaster via Sir2 and FoxO Activation

“…Many pharmacological interventions used for their anti-aging effects increase the resistance to environmental stresses [17,18]. A recent study showed that supplementation with BetA increased the resistance to various environmental stresses in C. elegans [10]. To confirm that the beneficial effects of BetA against various stressors were conserved in the current organism model, the effects of BetA treatment on stresses, including heat shock, cold shock, oxidative stress, and starvation stress, were investigated (Figure 4).…”

“…Extensive research in recent years has shown that it has antioxidant, anti-inflammatory, antiviral, and anticancer properties, making it an interesting subject for an investigation into its potential influence on lifespan [2,8,9]. Specifically, a recent study proved that BetA has an effect on longevity with an improvement in the healthspan due to its increased antioxidant activity and through its effects on the insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway in Caenorhabditis elegans, a free-living nematode [10]. However, there is no evidence on whether BetA affects longevity in other organism models.…”

A novel peptide derived fromHaematococcus pluvialisresidue exhibits anti-aging activity inCaenorhabditis elegans viathe insulin/IGF-1 signaling pathway

“…Pharyngeal pumping rates were measured based on previous studies. 23,24 Nematodes were placed on the surface of NGM plates with OP50, and the number of pharynx pumps was observed within 30 s, and counted on days 5, 10, and 15. Approximately 10 nematodes were randomly determined on each plate.…”