Obesity fast-forwards your biological clock—but science now shows a strict keto diet can roll it back. This breakthrough study reveals how shedding weight with VLCKD can actually slow or even reverse epigenetic aging by over six years.
Study: Epigenetic Aging Acceleration in Obesity Is Slowed Down by Nutritional Ketosis Following Very Low-Calorie Ketogenic Diet (VLCKD): A New Perspective to Reverse Biological Age. Image Credit: Shutterstock AI Generator / Shutterstock.com
A recent Nutrients study determines the association between obesity and epigenetic acceleration of biological age and the role of a very-low-calorie ketogenic diet (VLCKD) in modulating biological aging through epigenetic mechanisms.
Obesity and epigenetic aging
Oxidative stress, low-grade chronic inflammation, and mitochondrial dysfunction are observed in both obesity and aging. Obesity also influences epigenetic patterns of aging and may accelerate this process at both the molecular and cellular levels.
The epigenetic clock, which is based on DNA methylation patterns, is considered the most accurate predictor of biological age. This approach has evolved from the first-generation clocks of Horvath and Hannum to the second-generation PhenoAge, which is capable of quantifying any potential differences between biological and chronological age.
Clarifying the molecular mechanisms shared by accelerated aging and obesity may facilitate the development of more personalized and effective therapies to decelerate or reverse this process.
About the study
The current study's researchers investigated whether following a VLCKD could decelerate obesity-induced biological aging.
Horvath, Hannum, and Levine's epigenetic clocks were used to quantify biological age. The difference between chronological age (ChronoAge) and estimated biological age (DNAmAge) was used to reflect epigenetic acceleration (AgeAccel). The association between body mass index (BMI) and other metabolic parameters and epigenetic age was also determined.
The obesity and normal-weight groups comprised 28 and 20 study participants, respectively. A longitudinal cohort of 10 obese study participants who followed a VLCKD for six months was also included in the analysis.
Blood samples were collected at baseline, (BL), day 30, which was designated as nutritional ketosis (NK), and the endpoint on day 180 (EP) to perform epigenetic analysis.
Obesity accelerates epigenetic aging
Higher DNAmAge was observed in obese individuals as compared to normal-weight participants. The discrepancies between ChronoAge and DNAmAge in the groups were similar when comparing men and women.
AgeAccel was significantly higher in the obese group. The average deceleration of epigenetic age among normal-weight individuals was −3.1 years, compared to an average AgeAccel of +4.4 years for the obese group.
A statistically significant positive correlation was observed between AgeAccel and BMI, thus suggesting the existence of a relationship between accelerated biological aging and obesity. These findings confirm the role of obesity in epigenetic aging and how epigenetic clocks could be used as biomarkers for predicting health risks related to obesity.
How VLCKD reverses epigenetic aging
Among obese patients following a VLCKD, reduced DNAmAge, which was estimated using the Horvath, Hannum, and Levine epigenetic clocks, was observed. A significant reduction in DNAmAge was also observed in the NK and EP phases.
The average body weight loss in the NK and EP phases was nine and 20 kg, respectively. These results were consistent across genders at all time points. As in the cross-sectional cohort, the DNAmAge of obese patients at baseline was higher than their ChronoAge.
During the NK phase, the VLCKD group experienced an average deceleration in epigenetic age of -6.1 years. This deceleration persisted during the EP phase at -6.2 years, with similar benefits observed between men and women. This partial reversal of AgeAccel significantly correlated with BMI changes.
At the NK phase, β-hydroxybutyrate (β-OHB) levels were measured, following which a significant negative correlation was observed between lower AgeAccel and higher ketonemia. Thus, the observed deceleration in epigenetic aging could be associated with increased activity of ketone bodies during the NK phase.
AgeAccel attenuation was also associated with improved glucose, insulin, total cholesterol, and triglyceride levels in obese patients following a VLCKD.
Our findings underscore the therapeutic potential of VLCKD in the treatment of obesity, beyond body weight loss, as this nutritional strategy provides metabolic, anti-inflammatory, and antioxidant benefits.”
Conclusions
The study findings indicate the important role of epigenetic clocks in monitoring epigenetic aging associated with obesity. Furthermore, obese patients following a VLCKD experienced a deceleration in estimated biological age that was associated with metabolic parameters, BMI, and ketonemia.
Nevertheless, future studies with longer follow-up times and larger sample sizes are needed to confirm these observations and clarify the role of ketone bodies in the epigenetic regulation of aging.
Journal reference:
- Izquierdo, A. G., Lorenzo, P. M., Costa-Fraga, N., et al. (2025). Epigenetic Aging Acceleration in Obesity Is Slowed Down by Nutritional Ketosis Following Very Low-Calorie Ketogenic Diet (VLCKD): A New Perspective to Reverse Biological Age. Nutrients 17(6) 1060. doi:10.3390/nu17061060