How to slow down the ticking clock

Arthur Clément, longevity specialist from the Healthy Longevity Medicine Society, discusses evidence-based interventions to extend healthspan.

The average lifespan is steadily increasing worldwide [1]. However, healthy life expectancy hasn’t kept pace [2], resulting in longer periods of morbidity and increased social and economic burden [3]. So these extra years come at the cost of declining health, function, and independence [4].

My motivation is clear: to empower both patients and practitioners with actionable solutions, backed by the best science, to improve healthspan.

When should we start ?

Aging does NOT progress in a straight line. Science indicates there are three “peaks” or critical periods in the aging trajectory, starting as early as age 30 [5], where interventions might have especially strong impacts. This means good habits, initiated from your 30s, are more than just advisable, they’re transformative. Small, consistent improvements accumulate.

As per Lehallier, B., Gate, D., Schaum, N. et al. Undulating changes in human plasma proteome profiles across the lifespan.

A good physician in longevity medicine is more than a knowledge source, it’s a trusted partner who can inform, inspire, guide, motivate and support patients throughout their journey.

What can be done to measure where we individually stand?

Even if there is widespread advice, confusion persists about what actually works in slowing down biological aging. And in longevity medicine, patient involvement is not just helpful, it’s essential. So, before we can intervene effectively, we first need accurate ways to measure where we stand!

Aging is a complex phenomenon driven by at least 12 biological hallmarks, with epigenetic alterations being one of them and playing a central role [6].

Epigenetic clocks, biomarkers tracking DNA methylation changes, have proven themselves to be accurate at predicting biological age [7]. These clocks outperform traditional markers, like telomere length or frailty indices, in predicting health outcomes and mortality risk [8,9].

First-generation epigenetic clocks, developed from 2013 such as the Hannum and Horvath clocks and then the Zbieć-Piekarska clock, efficiently measure chronological age by analyzing specific DNA methylation patterns and are highly accurate across multiple tissues and cell types. Next-generation clocks, such as PhenoAge, GrimAge or DunedinPACE, were trained to predict health outcomes, disease risk, and mortality beyond simple chronological measurement [10].

The gap between biological and chronological age reflects risk factors that can be modified. This is why clocks and any reliable tool that can track biological age and improvements are so promising. These tools have the unique power to engage patients meaningfully, a necessity in longevity medicine.

Epigenetic clocks are an efficient way that allow patients to measure where they stand and improve their mortality risk.

How can we efficiently slow or reverse biological aging to potentially extend the years we live in good health?

Despite widespread advice about healthy living – diet, exercise, stress management – there remains confusion among both patients and practitioners about what actually works to slow the biological aging process. That’s why the goal of this piece is simple: to bring clarity.

By reviewing the current evidence in the latest literature and clinical experience behind biological aging markers – particularly epigenetic clocks – and evaluating how different interventions affect them, we can start to separate promising strategies from hopeful hype.

Dietary and lifestyle interventions

Comprehensive diet & lifestyle programs: An 8-week plant-rich diet, exercise, optimized sleep, stress management, and targeted supplements reduced Horvath DNAmAge by 3.23 years in healthy men [11] and 4.60 years in women [12].
Mediterranean Diet: A 24-month intervention reduced GrimAge by 0.66 years [13], with significant rejuvenation effects in specific subgroups like Polish women and epigenetically older individuals [14].
Polyphenol-rich foods, fasting, probiotics: These strategies reduced epigenetic age using Horvath clock by an average of -1.21 years [15].
Caloric restriction (reducing energy intake by 25% below their individual baseline for a duration of two years in healthy, non-obese adults) : Slowed DunedinPACE – another measure of biological aging – though not all clocks changed significantly [16].

Pharmacological Interventions

Vitamin D3 supplementation: Doses of 2,000–4,000 IU/day over 16 weeks decreased Horvath DNAmAge by nearly 2 years in overweight African Americans [17].
Growth hormone (0.015 mg/kg body weight daily) + metformin (500 mg twice daily) + DHEA (50 mg daily): A 12-month protocol reversed Horvath/PhenoAge/GrimAge clocks by over two years in older adults [18].
Metformin alone (500mg / day for at least 5 years): Associated with slower epigenetic aging (Hannum/Horvath) by up to 3.43 years in male diabetes patients [19].
Combined supplementation during 12 weeks showed significant effects on epigenetic age in older adults with accelerated aging [20].
Vitamin D (2000 IU/day), Omega-3 (1 g/day), Exercise Combinations (3x/week 30 min strength training) : Additive benefits on PhenoAge, highlighting the importance of synergy in intervention [21].

Exercise, weight loss, relaxation

Physical activity: Regular exercise correlates with slower Horvath/GrimAge acceleration (p 22,23].
Structured weight loss: An 18-month program reduced epigenetic aging (Horvath/GrimAge) by 7.1 months, particularly in older men [24].
Bariatric surgery: Demonstrated significant molecular changes in severely obese individuals [25].
Relaxation training showed a non-significant trend toward reduced aging using the Zbieć-Piekarska clock [26].

Depending on where you stand as a patient, there are some personalized interventions that can extend your healthspan.

What are the challenges remaining?

Even with the remarkable promise shown by epigenetic clocks, practical challenges remain:

Regulatory status: Epigenetic clocks are not yet standardized as regulatory biomarkers. This poses challenges for trial design, funding, and patient access – especially in jurisdictions where aging is not classified as a treatable condition.
Variability: Results can differ by clock type, genetic background, age, sex and exhibit intra-individual variability that can affect the reliability of tracking changes over time.
Short-duration studies: Most research runs less than two years; durability needs confirmation from longer Randomized Control Trials like CALERIE.
Clinical application: While drops in epigenetic age are promising, definitive links to lower morbidity/mortality need more data.
Standardization and personalization: We need standardized clock methodologies and tailored approaches that account for individual differences.
Multi-faceted interventions research: There is a need for more research exploring multi-faceted interventions (such as combining diet with senolytics) to understand additive or synergistic effects.

Above all, it’s crucial to develop tools that both patients and clinicians can confidently rely on, enabling people to track their progress and maintain motivation.

What is the ideal direction?

The growing momentum in aging science is bringing us closer to a future where everyone, regardless of background, can benefit from these advances. For the field to reach its potential, expanding accessibility is key. By developing clear clinical guidelines, scalable care models, and cost-benefit analyses, we can ensure that effective personalized interventions are accessible to all.

Bridging the gap between emerging biomarkers and practical longevity care will be a defining challenge of the coming decade

Imagine a world where every patient can confidently track their own health trajectory and witness the tangible benefits of evidence-based actions to extend their healthspan.

Conclusion

Epigenetic clocks represent the most accurate tools available today to assess biological age, disease and mortality risk. Consistent reductions through personalized interventions show real potential to extend healthy years. Experts need to help make these tools available to as many patients as possible by working on regulatory frameworks in countries where they are not yet widespread and improving accessibility in others.

About Arthur Clément

Dr Arthur Clément is a French Medical Doctor with over a decade of clinical and laboratory leadership experience. He is the director of Laboratoire Clément in Paris, a high-complexity diagnostic and IVF network of medical laboratories. After training in Paris and New York – including a fellowship at Weill Cornell Medicine – Dr Clément has had an extensive publication record and now advises clinics, diagnostics labs and health-tech startups across Europe and the UAE. He is also a member of the Healthy Longevity Medicine Society, and he is deeply committed to translating the science of aging and healthspan into practical strategies that improve patient outcomes.

How to slow down the ticking clock

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