Tree Bark Polysaccharides Slow Aging in Worms and Flies Through FOXO and Nrf2 Pathways

A natural compound extracted from the bark of an African rainforest tree appears to slow the biological machinery of aging, according to new research published in the journal Biogerontology. Scientists at Heilongjiang University of Chinese Medicine report that polysaccharides isolated from Pausinystalia macroceras (K. Schum.) Pierre, a species related to the yohimbe tree of Central Africa, extended lifespan and improved healthspan in two of biology’s most widely used aging models: the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. The findings place this largely overlooked tree species alongside a growing roster of plants whose complex carbohydrates show genuine longevity-modulating activity, and they trace the effect to two of the most conserved stress-response circuits in animal biology.

The appeal of plant polysaccharides in aging research lies partly in their safety profile. Unlike synthetic pharmacological candidates such as rapamycin or metformin, which raise long-term safety and dosing questions for otherwise healthy people, polysaccharides are typically low in toxicity and highly biocompatible. Yet their mechanisms have remained stubbornly opaque. The new study set out to close that gap by testing whether polysaccharides from P. macroceras, abbreviated PMP by the researchers, could delay aging without compromising growth, feeding, or reproduction — a critical distinction, since simply poisoning an organism or starving it can also lengthen life at a devastating cost to vitality.

Across the experiments, PMP delivered a coherent anti-aging signature. Supplemented worms and flies lived longer than untreated controls, and importantly, the extra days were healthy ones. Treated animals retained better locomotor performance, preserved physiological fitness, and did not suffer measurable harm to feeding behavior or reproductive output. This combination — lifespan extension alongside maintained healthspan — is the benchmark that gerontologists look for when judging whether a compound is a true aging modulator rather than a narrow toxicological artifact. The researchers also observed that PMP-treated animals withstood a range of environmental stresses more effectively than their peers, a hallmark of enhanced cellular resilience.

Zooming into the cell, the study documented the biochemical details of that resilience. Aging tissues accumulate reactive oxygen species, the chemically unstable byproducts of metabolism that damage DNA, proteins, and membranes. Aging is also marked by the failure of proteostasis, the cellular system that folds, repairs, and disposes of proteins, allowing damaged molecules and aggregates to pile up. In PMP-supplemented animals, intracellular reactive oxygen species accumulation dropped, the age-pigmented waste product lipofuscin accumulated more slowly, and polyglutamine protein aggregation — the same class of clumping implicated in Huntington’s disease — was attenuated. Redox balance and protein homeostasis, two pillars of cellular youth, were thus demonstrably shored up.

The mechanistic core of the paper concerns two transcription factors that sit at the top of animal longevity networks. In C. elegans, DAF-16 is the worm equivalent of the mammalian FOXO family, a set of transcription factors long known to govern lifespan in response to insulin-like signaling. SKN-1 is the worm’s version of Nrf2, the master regulator of antioxidant and detoxification gene expression in animals from worms to humans. The study found that PMP treatment enhanced signaling through both pathways, and that this activation propagated downstream: levels of the antioxidant enzymes SOD-3, a superoxide dismutase, and GST-4, a glutathione S-transferase, increased in treated animals. In other words, the compound did not merely mop up free radicals chemically; it appeared to switch on the animals’ own genetic antioxidant defense programs.

This distinction matters for how the research community interprets the result. Many antioxidant molecules fail in translation because scavenging reactive species directly is a blunt instrument that can interfere with the beneficial signaling roles these molecules play. Compounds that instead engage the Nrf2 and FOXO transcriptional circuitry, prompting cells to upregulate their own coordinated defensive machinery, are considered more plausible candidates for safe intervention. The authors frame PMP within this mechanistic tradition, connecting it to a body of work in which other plant polysaccharides — from species including Lycium barbarum, Dendrobium officinale, Angelica sinensis, and lentinan-producing mushrooms — have been shown to act on the same conserved pathways.

Beyond oxidative stress and proteostasis, the study reached into metabolism, an increasingly central theme in aging biology. Using metabolic profiling, the researchers found that PMP alleviated age-associated metabolic disturbances, modulating amino acid metabolism, carbohydrate metabolism, and energy metabolism in treated animals. Metabolic drift — the gradual erosion of the finely tuned balance of metabolites that sustains physiological function — is one of the quiet engines of aging, and interventions that preserve this homeostasis are thought to support the entire edifice of healthspan. The finding suggests PMP’s effects are systemic rather than confined to a single stress-response module, coordinating longevity signaling, stress resistance, and metabolic regulation simultaneously.

The choice of two model organisms strengthens the case considerably. C. elegans, a millimeter-long soil nematode, and Drosophila melanogaster, the vinegar fly, separated by hundreds of millions of years of evolution, nevertheless share the core signaling modules that control aging, including insulin/IGF-1 signaling, FOXO transcription factors, and Nrf2-type stress responses. When a compound produces consistent, mechanistically aligned effects in both species, the probability that the finding reflects a general biological principle rather than a quirk of one organism’s physiology rises sharply. It also builds confidence for the long road toward mammalian studies, where any putative anti-aging intervention must ultimately prove itself.

The work also carries conservation and ethnopharmacology dimensions. Pausinystalia macroceras grows in the forests of Central Africa, where its relative Pausinystalia johimbe has long been harvested for bark containing yohimbine. The present study shifts attention from the tree’s alkaloids to its polysaccharides, high-molecular-weight carbohydrates whose biological activities in aging contexts are only beginning to be catalogued. If such compounds continue to demonstrate longevity benefits with minimal toxicity, they could become attractive starting points for nutraceutical or functional food development — though the researchers and the field at large are careful to note that effects in worms and flies do not guarantee equivalent outcomes in humans, and that the dose-response relationships, bioavailability, and long-term safety of PMP remain to be established.

For now, the study offers something the aging research community prizes: a natural molecule, a reproducible phenotype across species, and a plausible molecular mechanism anchored in the DAF-16/FOXO and SKN-1/Nrf2 axes, with downstream antioxidant, proteostatic, and metabolic consequences. As the global population ages and the burden of age-related disease grows, the search for interventions that extend not just lifespan but healthspan has become a research priority. Compounds like PMP — drawn from traditional botanical sources, interrogated with modern molecular genetics, and validated across evolutionary distant models — represent one of the most active frontiers in that search. The next steps, extending this work into vertebrate systems and dissecting the structure-activity relationships of the polysaccharides themselves, will determine whether the modest worm and fly in the laboratory have once again pointed the way toward something medically meaningful.

Subject of Research: Aging-modulatory effects of Pausinystalia macroceras polysaccharides acting through DAF-16/FOXO and SKN-1/Nrf2 signaling in C. elegans and Drosophila aging models

Article Title: Aging-modulatory effects of Pausinystalia macroceras (K. Schum.) Pierre polysaccharides are associated with DAF-16/FOXO and SKN-1/Nrf2 signaling in multiple aging models

Article References: Aging-modulatory effects of Pausinystalia macroceras (K. Schum.) Pierre polysaccharides are associated with DAF-16/FOXO and SKN-1/Nrf2 signaling in multiple aging models. (n.d.). https://doi.org/10.1007/s10522-026-10509-x

Image Credits: AI Generated

DOI: 10.1007/s10522-026-10509-x

Keywords: Pausinystalia macroceras, polysaccharides, aging, longevity, DAF-16/FOXO, SKN-1/Nrf2, Caenorhabditis elegans, Drosophila melanogaster, oxidative stress, proteostasis, healthspan, antioxidant defense