A new study from Spain has shed light on a fascinating connection between obesity and epigenetic ageing, revealing how dietary interventions may hold the key to reversing molecular ageing. This research, published in the journal Nutrients, delves into the intricate relationship between obesity and accelerated biological ageing, offering intriguing insights into how a very low-calorie ketogenic diet could potentially turn back the clock at the molecular level.
Epigenetic ageing refers to how the body ages internally, often independent of chronological age. It’s a measurement rooted in molecular changes that influence gene expression without altering the underlying DNA sequence. While chronological age is determined by the number of years a person has lived, epigenetic ageing reflects the wear and tear on the body at a cellular level. When biological age overtakes chronological age, individuals may face heightened risks of chronic diseases and premature mortality. This disparity, often linked to obesity, underscores the importance of strategies aimed at addressing accelerated ageing.
Obesity remains a significant health challenge. Its implications extend far beyond physical appearance, impacting various bodily systems and accelerating processes like inflammation, oxidative stress, and mitochondrial dysfunction. These processes contribute to faster cellular deterioration, hastening biological ageing and increasing vulnerability to chronic conditions such as diabetes, cardiovascular disease, and cancers.
The Spanish study focused on whether nutritional interventions, specifically a very low-calorie ketogenic diet (VLCKD), could mitigate this accelerated ageing. Ketogenic diets, characterised by extremely low carbohydrate intake (typically under 50 grams per day), aim to induce metabolic ketosis—a state in which the body burns fat for energy rather than relying on carbohydrates. Historically employed to manage epilepsy, ketogenic diets have gained popularity for their potential weight-loss benefits. However, their restrictive nature has sparked debate among experts regarding long-term safety and impact on cardiovascular health.
In the study, researchers analysed two distinct cohorts to examine epigenetic ageing patterns: a cross-sectional cohort and a longitudinal cohort. The cross-sectional group consisted of two subgroups—one with individuals of normal weight and the other with individuals classified as obese. Meanwhile, the longitudinal cohort involved obese participants undergoing a VLCKD for 180 days. Blood samples were collected at baseline, after 30 days on the diet, and at the 180-day mark to assess biological age using established age clocks such as Horvath, Hannum, and Levine models.
Initial findings revealed stark contrasts in biological ageing between normal-weight and obese individuals. The normal-weight group exhibited an epigenetic age deceleration of 3.1 years compared to their chronological age—a sign of healthier molecular ageing. Conversely, those with obesity demonstrated an accelerated epigenetic age of 4.4 years above their chronological age. These differences highlight how obesity exacerbates cellular stress and inflammation, driving premature ageing.
Encouragingly, results from the longitudinal cohort offered hope for reversing this trend. At the 30-day mark on the VLCKD, participants showed an average epigenetic age deceleration of 6.1 years—a significant improvement. At the end of the 180-day period, this deceleration was sustained, averaging 6.2 years. Researchers attributed these effects to nutritional ketosis, suggesting that elevated levels of beta-hydroxybutyrate—a ketone body produced during ketosis—might play a role in slowing biological ageing.
Beyond molecular ageing, participants experienced improvements in glucose and insulin levels—critical markers for metabolic health. These findings are especially important given that individuals with obesity face heightened risks for type 2 diabetes and other metabolic disorders.
While these results are promising, experts emphasise caution in interpreting them as definitive evidence that VLCKD alone drives biological age reversal. Weight loss itself has been shown to improve overall health outcomes and extend lifespan across various dietary approaches. The study raises questions about whether ketosis-related mechanisms or general weight reduction underlie these benefits.
The safety and sustainability of VLCKDs also warrant scrutiny. These diets involve severe calorie restriction—typically under 800 kilocalories per day—and high fat intake. Without proper medical supervision, they may pose risks such as nutrient deficiencies, electrolyte imbalances, or even ketoacidosis. Long-term data on their safety remains limited, particularly for vulnerable groups such as older adults or individuals with pre-existing kidney issues.
Experts suggest that further research is needed to validate these findings and explore the broader implications for dietary guidelines. Larger studies could help reinforce the role of ketone bodies in epigenetic regulation and determine whether VLCKDs can be safely integrated into clinical practice. Until then, caution is advised when adopting extreme dietary measures without professional oversight.
Despite its limitations, this study adds to the growing body of evidence connecting obesity with accelerated biological ageing. It underscores the importance of addressing obesity not only for physical health but also for its molecular impacts. While VLCKDs offer intriguing possibilities, balanced approaches to weight management—incorporating diverse food groups and sustainable practices—remain central to promoting long-term health.
As researchers continue to investigate innovative solutions for reversing epigenetic ageing, this study serves as a reminder that nutritional choices can profoundly shape our biological destiny. Whether through ketogenic diets or other interventions, understanding the interplay between diet, metabolism, and molecular ageing presents exciting opportunities for improving health outcomes across populations.
