The stakes are considerable. Skeletal muscle is the body’s largest protein reservoir and its principal site of glucose disposal, and its maintenance underpins metabolic health and healthy aging. After the age of 50, muscle mass typically declines by 1 to 2 percent per year and strength by 1.5 to 3 percent, a loss that culminates in sarcopenia, a condition linked to disability and increased mortality. With the global population aged 65 and over projected to exceed 1.5 billion by 2050, sarcopenia has become a leading public health concern. What is changing the field, however, is the recognition that chronological age is not the only driver. Environmental exposures, particularly endocrine-disrupting chemicals, are increasingly implicated in the premature onset of muscle degeneration, and human studies have associated the burden of these chemicals with lower muscle mass, reduced strength, and even acceleration of biological age.

BPA is among the most prevalent of these chemicals. It leaches continuously from polycarbonate plastics, epoxy-resin can linings, thermal paper receipts, and medical devices, making human exposure effectively unavoidable. Experimentally, BPA reproduces three features of degenerative muscle aging. It promotes mitochondrial dysfunction and excess generation of reactive oxygen species, which damage macromolecules including DNA. It impairs the proliferation and differentiation of C2C12 myoblasts, a widely used mouse muscle cell line, and reduces myotube formation, the cellular process by which individual muscle cells fuse into functional fibers. And chronic exposure shortens survival and impairs locomotor performance in model organisms. These three axes are not independent: redox imbalance itself modifies myogenic differentiation and anabolic signaling, which means an intervention acting on the antioxidant response could plausibly influence the entire muscle-building program.

The Thai team, led by Woorawee Inthachat and colleagues at Mahidol University, began with the peel itself. Pomelo, Citrus maxima, is the largest of the citrus fruits, and its peel is rich in flavonoids such as naringin, hesperidin, and neohesperidin, along with phenolic acids and coumarins. Rather than using conventional hours-long solvent extraction, the researchers applied microwave-assisted extraction optimized through a Box-Behnken design and response surface methodology, testing 15 combinations of ethanol concentration, microwave power, and extraction time. The winning condition, 70 percent aqueous ethanol at 600 watts for just 60 seconds, yielded a total phenolic content of 21.98 milligrams of gallic acid equivalent per gram of dry weight, notably higher than the 15.79 milligrams obtained from the same peel with a four-hour water bath extraction in earlier work. The microwave’s internal superheating ruptures plant cell walls and accelerates mass transfer, compressing a process that once took hours into a single minute and cutting energy consumption in the bargain.

Chemical profiling by liquid chromatography with tandem mass spectrometry revealed that naringenin dominated the extract after acid hydrolysis, reaching 2,722.60 micrograms per gram of dry weight, with smaller amounts of apigenin and isorhamnetin. Because these aglycones appeared only after hydrolysis, the flavonoids in the native peel exist mainly as glycosides. The extract also showed strong antioxidant activity, particularly in the oxygen radical absorbance capacity assay, which registered 1,198.39 micromoles of Trolox equivalent per gram of dry weight. Armed with this characterization, the team turned to whole organisms, feeding the extract to Canton-S fruit flies at 125 and 250 micrograms per milliliter, alongside two positive controls: resveratrol, a well-characterized anti-aging compound, and naringenin at the dose corresponding to its concentration in the higher extract dose.

The fly results were striking. Chronic exposure to 0.05 millimolar BPA slashed median survival from about 28 days to 19 days in females and 17 days in males, a roughly 40 percent reduction. Co-supplementation with the pomelo peel extract at 250 micrograms per milliliter pushed median survival back to 24.33 days in females and 22.00 days in males, an effect statistically comparable to the positive controls. A feeding assay confirmed the benefit was not an artifact of caloric restriction or food avoidance. BPA also devastated climbing ability, a functional proxy for neuromuscular integrity, but flies receiving the extract maintained climbing indices close to unexposed controls through day 14. At the molecular level, BPA induced the antioxidant genes Cat, Sod1, and Gstd1, the master redox regulator Cnc, the fly homolog of mammalian Nrf2, and the DNA repair gene Ogg1, all hallmarks of a systemic oxidative stress response. The extract returned these transcripts toward baseline and lowered measured reactive oxygen species, while also normalizing Him, a gene whose product inhibits the myogenic transcription factor Mef2 and whose overexpression promotes muscle degeneration.

In parallel, the researchers tested the extract in C2C12 mouse myoblasts differentiating in the presence of 40 micromolar BPA, a concentration chosen because it substantially impairs muscle cell function without causing generalized cytotoxicity. BPA alone left the cells predominantly triangular and mononuclear, with little conversion into elongated, multinucleated myotubes. Co-treatment with the extract at 30 to 50 micrograms per milliliter significantly restored the fusion index, the proportion of nuclei incorporated into multinucleated myotubes, and recovered muscle fiber diameter to values comparable to or slightly above the differentiated control. Western blotting showed that BPA reduced the myogenic transcription factors myogenin and MEF2A, and that the extract significantly increased MEF2A at 20 and 30 micrograms per milliliter. The extract also reactivated the Akt/4E-BP1 anabolic signaling axis, a key regulator of muscle protein synthesis that BPA is known to suppress, raising phospho-Akt at three doses and phospho-4E-BP1 at an intermediate dose.

One nuance deserves attention. The extract was not biologically inert in healthy flies. In males, supplementation alone caused a mild but statistically significant reduction in median lifespan of roughly 13 to 15 percent, without a clear dose-response pattern. The authors interpret this through the lens of mitohormesis: low levels of reactive oxygen species serve essential signaling functions in unstressed organisms, and excessive antioxidant activity can suppress these beneficial signals. The pattern also reflects sexual dimorphism in fly metabolism and detoxification, and possibly the estrogenic activity of naringenin, which can bind both subtypes of the mammalian estrogen receptor and influence muscle cell differentiation. Fruit flies lack classical estrogen receptor signaling, so the fly and cell results may arise through partly different mechanisms. The practical implication is that pomelo peel extract is better regarded as a protective intervention under conditions of oxidative stress or pollutant exposure than as a general lifespan-promoting supplement for healthy individuals, and formal safety margins would need to be established before any functional-food development.

The study also has honest limits. The concentrations used are proof-of-concept exposures rather than human-equivalent doses, although the estimated naringenin levels fall within the low-micromolar range measured in human plasma after citrus consumption. Humans are exposed to complex mixtures of endocrine disruptors, not a single chemical, and the researchers did not measure direct oxidative DNA damage, antioxidant enzyme activities, or canonical atrophy markers such as MuRF1 and Atrogin-1. Notably, the extract did not reduce BPA-induced reactive oxygen species in the differentiating muscle cells even as it restored myogenesis, suggesting the cellular protection may operate through redox-sensitive signaling rather than direct radical scavenging, a distinction that remains to be tested directly.

Even with those caveats, the convergence of evidence is compelling: a one-minute microwave extraction of an agricultural waste product, optimized by statistical design, extended survival and preserved muscle function in BPA-poisoned flies while rebuilding muscle fibers and anabolic signaling in poisoned muscle cells. If further validation in mammalian models holds up, the humble pomelo peel, currently composted or burned by the ton, could become a nutraceutical resource for mitigating the muscle-wasting and accelerated aging that our chemical environment increasingly imposes. It is a vivid example of circular economy science at its most concrete: turning trash into a shield against the toxic legacy of the plastics age.

Subject of Research: Protective effects of optimized pomelo peel extract against bisphenol A-induced oxidative stress, premature aging, and impaired muscle cell differentiation

Article Title: Valorization of microwave-assisted optimized pomelo peel extract mitigates bisphenol A–induced oxidative stress and premature aging in Drosophila and disruption of myogenesis in C2C12 cells

Article References: Inthachat, W., Wudtiwai, B., Umsumarng, S., Buacheen, P., Thangsiri, S., Suttisansanee, U., Pitchakarn, P., & Temviriyanukul, P. (2026). Valorization of microwave-assisted optimized pomelo peel extract mitigates bisphenol A–induced oxidative stress and premature aging in Drosophila and disruption of myogenesis in C2C12 cells. Journal of Agriculture and Food Research, 31, Article 103318. https://doi.org/10.1016/j.jafr.2026.103318

Image Credits: AI Generated

DOI: 10.1016/j.jafr.2026.103318

Keywords: pomelo peel, bisphenol A, endocrine disruptors, oxidative stress, sarcopenia, Drosophila, C2C12 myoblasts, naringenin, microwave-assisted extraction, antioxidants, myogenesis, healthy aging