Green Tea Compound EGCG Slows Biological Aging Through Peroxisome Activation

A large analysis of United States national health survey data has linked higher intake of epigallocatechin gallate, the most abundant catechin in green tea, to slower biological aging and lower all-cause mortality, and a new study pairs that epidemiological signal with experiments in worms and mouse liver cells to propose a mechanism centered on a long-overlooked organelle: the peroxisome. The work, published in Aging Cell, reports that EGCG intake was inversely associated with PhenoAge acceleration, a blood-based measure of biological age, and that in laboratory models the compound extended lifespan and health span by promoting peroxisome biogenesis and peroxisomal fatty acid beta-oxidation.

The human side of the study drew on National Health and Nutrition Examination Survey cycles from 2007–2008, 2009–2010, and 2017–2018, covering 10,977 adults aged 20 and older. PhenoAge was estimated from chronological age and nine routine blood biomarkers, including albumin, alkaline phosphatase, creatinine, glucose, C-reactive protein, lymphocyte percentage, mean cell volume, red cell distribution width, and white blood cell count. PhenoAge acceleration, the residual from regressing PhenoAge on chronological age, served as the primary outcome. Among the six dietary catechins assessed, EGCG ranked first in predictive importance for PhenoAge acceleration in both partial least squares regression and random forest modeling, so it was carried forward for analysis.

Dietary EGCG exposure in this population was strikingly low and skewed. Overall, 35.1 percent of participants reported no EGCG intake at all, and the median intake across the full sample was just 0.16 milligrams per day. Tea-based foods and beverages accounted for 99.55 percent of estimated intake, with black tea contributing 41.00 percent, tea of unspecified type 40.18 percent, and green tea 18.03 percent. Because intake among consumers was so right-skewed, the researchers split consumers at the median into low and high groups, at or below 1.42 and above 1.42 milligrams per day, producing three roughly equal-sized categories alongside the non-consumers.

In fully adjusted weighted multivariable linear regression, low and high EGCG intake were each associated with lower PhenoAge acceleration relative to non-consumers, with differences of −0.53 years (95 percent confidence interval −0.99 to −0.08) and −0.62 years (95 percent confidence interval −1.06 to −0.17), respectively. Restricted cubic spline analysis showed a linear inverse association between log10-transformed EGCG intake and PhenoAge acceleration, with an overall p value of 0.003 and no evidence of nonlinearity. The association held in sensitivity analyses that excluded extreme energy intakes, applied propensity score weighting, or modeled intake as a continuous variable, and it was not modified by age, sex, race, poverty-to-income ratio, smoking, alcohol consumption, physical activity, hypertension, or diabetes.

Mortality findings pointed in the same direction. Over a mean follow-up of 7.9 years, during which 1,276 deaths occurred, fully adjusted weighted Cox models yielded hazard ratios of 0.83 (95 percent confidence interval 0.69–0.99) for the low-intake group and 0.82 (95 percent confidence interval 0.68–0.99) for the high-intake group compared with non-consumers. Estimated residual life expectancy at age 45, calculated as the area under the survival curve from age 45 to 100, was higher among EGCG consumers, with estimated differences of 1.22 years (95 percent confidence interval 0.38–2.11) for low intake and 1.27 years (95 percent confidence interval 0.39–2.25) for high intake relative to non-consumers. The authors caution that EGCG estimates came from two self-reported 24-hour recalls, so habitual intake may be misclassified, and residual confounding remains possible.

To test whether EGCG could actually influence aging rather than merely track with it, the team turned to Caenorhabditis elegans. Supplementation with 100 to 300 micromolar EGCG significantly extended worm lifespan, with 200 micromolar producing the maximal effect, a 10.73 percent increase. The extension persisted when worms were fed heat-killed bacteria, indicating the effect did not depend on bacterial metabolism. In aged worms, EGCG also improved health span markers, attenuating age-related declines in pharyngeal pumping and body bending and reducing the accumulation of lipofuscin, an autofluorescent pigment associated with aging. RNA sequencing showed that EGCG enriched transcriptional programs related to longevity regulation, locomotion, and feeding behavior at both young and aged stages.

The mechanistic core of the paper emerged from transcriptomic comparisons. The researchers first identified genes whose expression declined with age in untreated worms, finding enrichment in terms related to locomotion, feeding behavior, lipid homeostasis, fatty acid beta-oxidation, and the peroxisome. They then asked whether EGCG reversed this decline. On adult Day 2, EGCG induced 3,158 differentially expressed genes, and on Day 8, 464. Trend analysis isolated a conserved set of 1,130 genes whose expression progressively fell in control worms but was restored by EGCG at both time points. KEGG analysis ranked the peroxisome pathway as the top-enriched pathway among these genes, and gene set enrichment analysis independently confirmed peroxisome pathway activation at both stages. Protein-protein interaction prioritization of peroxisome-annotated genes yielded a 20-gene network spanning peroxisomal beta-oxidation and peroxisome biogenesis, with hub genes including maoc-1, dhs-28, acox-1.1, acox-3, prx-5, and prx-19.

Functional tests then established that these transcriptional shifts matter for longevity. EGCG increased peroxisome abundance in intestinal reporter worms and upregulated ten peroxisome biogenesis genes, including prx-5 and prx-19, whose protein levels also rose. When the researchers knocked down prx-5, which mediates import of matrix proteins into peroxisomes, the punctate peroxisomal reporter signal became diffuse, consistent with impaired peroxisome formation, and crucially the knockdown abolished EGCG’s lifespan extension and its maintenance of pharyngeal and locomotor performance during aging. Similarly, EGCG upregulated nine peroxisomal beta-oxidation genes, increased acox-1.2 transcriptional activity and ACOX-3 protein levels, and shifted the lipid profile of worms toward reduced very-long-chain and long-chain fatty acids and acylcarnitines alongside increased short- and medium-chain acylcarnitines, a pattern consistent with enhanced peroxisomal beta-oxidation flux. Knockdown of dhs-28 or acox-1.2 likewise eliminated EGCG’s lifespan and health span benefits, and acox-1.2 knockdown or co-treatment with the antioxidant N-acetylcysteine blunted both the EGCG-induced transient hydrogen peroxide increase and the lifespan extension.

To probe whether the mechanism extends beyond worms, the team induced senescence in AML12 mouse hepatocytes with doxorubicin, a DNA-damaging agent. EGCG treatment reduced the fraction of senescence-associated beta-galactosidase-positive cells and lowered p21 and p16 protein levels. It also increased peroxisome abundance measured by PMP70 immunofluorescence and EGFP-SKL imaging, and raised protein levels of PEX5, PEX19, ABCD1, PMP70, and the beta-oxidation enzymes ACOX1, HSD17B4, EHHADH, and ACAA1. When Pex5 or Acox1 was knocked down by siRNA, EGCG’s ability to suppress p21 and p16 and reduce senescence-associated beta-galactosidase positivity was diminished, suggesting that peroxisome biogenesis and beta-oxidation contribute to the anti-senescent effect in mammalian cells as well.

The authors are careful about what these findings do and do not establish. Worm and cell results cannot be directly extrapolated to human aging, and experimental EGCG doses cannot be translated to human intakes given major interspecies differences in absorption and metabolism. Whether intact EGCG or metabolites produced by worms or their gut microbes mediate the effects remains unresolved, and the upstream link between EGCG and the peroxisomal program, potentially involving NHR-49/PPARα signaling, awaits genetic testing. Still, the convergence of population-level associations with loss-of-function evidence in two model systems makes a coherent case that peroxisome biogenesis and peroxisomal fatty acid beta-oxidation are functionally important components of the anti-aging response to EGCG, and it flags peroxisomal pathways as a plausible target for compounds aimed at promoting healthy aging.

Subject of Research: Association of dietary EGCG intake with biological aging and its peroxisome-centered geroprotective mechanisms in worms and mouse hepatocytes

Article Title: The Dietary Polyphenol Epigallocatechin Gallate Delays Biological Aging by Activating Peroxisome Biogenesis and Peroxisomal Fatty Acid β‐Oxidation

Article References: Huang, X., Yang, Y., Huang, F., Lin, W., Li, Q., Yuan, Y., & Zhu, P. (2026). The Dietary Polyphenol Epigallocatechin Gallate Delays Biological Aging by Activating Peroxisome Biogenesis and Peroxisomal Fatty Acid β‐Oxidation. Aging Cell, 25(11), Article e70795. https://doi.org/10.1111/acel.70795

Image Credits: AI Generated

DOI: 10.1111/acel.70795

Keywords: EGCG, green tea, biological aging, PhenoAge, peroxisome, fatty acid beta-oxidation, C. elegans, lifespan, cellular senescence, NHANES, AML12 hepatocytes, longevity