Obesity as a 'time accelerator': Molecular signals of premature aging found in 30-year-olds

Is it possible to “age” at the cellular level before you’re 30? A study in JAMA Network Open using data from a Chilean cohort shows that long-term obesity since childhood or adolescence in young people aged 28–31 is associated with a whole bunch of biomarkers of accelerated aging, from epigenetic clocks and telomere shortening to chronic inflammation. On average, the epigenetic age of “long-lived obese people” was 15–16% ahead of their passport age, and up to 48% ahead of their passport age in some participants.

Background of the study

Obesity increasingly begins not in adulthood, but in childhood and adolescence, turning from a “state of the here and now” into a long-term exposure. The longer the body lives in conditions of excess weight, the more metabolic and inflammatory stress accumulates, the so-called allostatic load is formed. In this context, the question is no longer just about kilograms and the risk of diabetes in a decade, but about whether long-term obesity accelerates the biological processes of aging themselves - long before clinical diagnoses.

In recent years, tools have emerged that allow us to test this quantitatively. These include epigenetic “clocks” (age assessment based on DNA methylation patterns), telomere length (a marker of cell division/stress), and a panel of “inflammatory aging” features (hs-CRP, IL-6, etc.). A number of studies in middle-aged adults have shown a link between increased BMI and metabolic syndrome and acceleration of these markers. But data in young adults are limited: these are often cross-sectional studies and short observations, where it is difficult to separate the effect of the duration of obesity from the current weight.

This is why longitudinal cohorts, followed from birth, are critical. They allow us to reconstruct body mass trajectories – when obesity began, how many years it lasts – and compare them with several “anchor” biomarkers of aging. This approach moves away from reduction to a single indicator and provides a systemic view: if the epigenetic clock is “fast”, telomeres are shorter, and inflammatory markers are higher already at 28-31 years, this is a strong argument in favor of the hypothesis of accelerated biological aging in long-term obesity.

The practical motivation is obvious. If the length of the “obesity” exposure predicts the “gap” between the passport and biological age in youth, then the window for prevention is childhood and adolescence. Early interruption of the obesity trajectory can not only reduce cardiometabolic risks, but also “synchronize the clock” - slow down the accumulation of biological wear and tear, which would otherwise manifest itself as chronic diseases already in the third or fourth decade of life.

What exactly did the scientists do?

• They took participants from the oldest Chilean cohort, the Santiago Longitudinal Study: 205 people aged 28-31 years, equally divided between men and women.
• They were divided into three groups according to their BMI (body mass index) trajectory from birth:
  1. Always healthy BMI (n=89)
  2. Obesity since adolescence (n=43; average duration ≈13 years)
  3. Obesity from early childhood (n=73; ≈27 years duration)
• Venous blood was collected, immune system cells were isolated and analyzed:
  • Epigenetic clock (Horvath and GrimAge) - based on methylation patterns of >850,000 DNA sites.
  • The length of telomeres (the end caps of chromosomes).
  • Panel of inflammatory cytokines, growth/metabolism hormones (IGF-1/2, FGF-21, GDF-15), adipo- and myokines (leptin, apelin, irisin, etc.).
  • Plus the “classic” risks: waist, blood pressure, insulin and HOMA-IR, lipids, arterial stiffness (PWV), liver (steatosis), etc.

Why trajectories and not a one-time BMI? Because the body reacts to the duration of the load. Ten years of obesity ≠ one year of obesity - this is a different "experience" for cells.

What is the epigenetic clock and telomeres

• Imagine DNA as a book, and methylation as stickers-bookmarks. Over the years, their pattern changes quite predictably. Mathematical models (Horvath clock, GrimAge) estimate biological age based on these "bookmarks".
• Telomeres are the protective tips of chromosomes. With each cell division, they shorten slightly. On average, shorter → older (although this is just one stroke of the portrait).

What they found: "clocks are running fast," shorter telomeres, higher inflammation

1) Epigenetic age is significantly ahead of passport age

• In people with long-term obesity:
  • Horvath age is higher than chronological age by ≈+4.4 years (≈+15%) for onset in adolescence and ≈+4.7 years (≈+16%) for onset in childhood.
  • For some participants, the difference reached +48% (!).
• Those who have been at a healthy weight their entire lives have an epigenetic age close to their passport age.

2) Telomeres are shorter

• Average values: 8.01 kb (healthy weight) versus 7.46-7.42 kb (long-term obesity).

For statisticians: Cohen's f effect sizes are large (≈0.65-0.81) for the epigenetic clock and telomeres.

3) "Inflammatory Aging" and Signaling Failure

• Inflammation: hs-CRP and IL-6 are significantly higher in obese groups (this is the so-called inflammaging).
• Nutrient signaling and mitostress: FGF-21 and GDF-15 are elevated (often increase with mitochondrial stress), IGF-1/IGF-2 are reduced (in young people, their lower levels are usually not good).
• Adipo-/myokines: higher levels of leptin, apelin, irisin - signs of problems in muscle-fat "negotiations" with other organs.
• TNF-α, GDF-11 - no significant differences.

4) Clinical background of 29-year-olds with long-term obesity

• Larger waist, higher systolic pressure, PWV, insulin, HOMA-IR/HOMA-β, lower HDL, more frequent liver steatosis (median Hamaguchi score ≈4).
• Interestingly, the groups “obesity since adolescence” and “since childhood” are almost indistinguishable in terms of damage – the key factor is duration, not the exact age of onset.

Why Obesity Can "Age" Cells

Briefly about the “ageing hallmarks” that emerged in the analysis:

1. Epigenetic changes - obesity is accompanied by hormonal and metabolic shifts that “rearrange the bookmarks” on DNA.
2. Telomere dynamics - chronic inflammation and oxidative stress accelerate shortening.
3. Chronic inflammation - visceral fat, as an endocrine organ, releases pro-inflammatory molecules.
4. Mitochondrial stress - the cell's energy stations operate in a "dirty" mode; FGF-21, GDF-15 increase as "distress signals".
5. Intercellular communication failure - changes in leptin/irisin/apelin, etc. distort the dialogue between muscles, fat, liver, brain, and blood vessels.
6. Disruption of nutrient signaling - the insulin/IGF axis, sensitivity to nutrient signals, autophagy - are all key levers of aging.

What does this mean in practice?

The bad news: with long-term obesity, the “biological clock” actually runs faster in some people – and already by the age of 30.

The good news: These clocks are sensitive to lifestyle. In other studies, improved sleep, reduced fat (especially visceral fat), regular physical activity, and calorie- and quality-controlled diets reduce inflammation and improve metabolic and epigenetic markers.

What is most often recommended (discuss with your doctor, especially for chronic diseases):

• Calorie deficit + diet quality: less ultra-processed, more whole foods, protein, fiber; control added sugar.
• Movement: combine aerobic (endurance) and strength (muscles = endocrine organ, myokines!). Even 150-300 min of moderate load/week + 2-3 strength sessions is already a lot.
• Sleep and Stress: Lack of sleep and chronic stress fuel systemic inflammation and cravings for high-calorie foods.
• Medical monitoring: blood pressure, lipids, glucose/insulin, liver. If indicated, discuss drug-induced weight loss (including modern drugs) and comorbidities.
• Sequence > ideality: the body cares about the sum of weeks and months in the “green zone”, not one “ideal” month.

Strengths and limitations of the work

Strengths:

• Real BMI trajectories from birth, not a one-time snapshot.
• A broad panel of molecular markers, not just one or two indicators.
• Large effect sizes (not statistically significant).

Restrictions:

• Observational study: shows association, not proven causation.
• Cohort from Chile: environment/ethnicity/diet - their own; transferability of conclusions requires caution.
• BMI is a crude metric (it does not show fat distribution), although it is practical.
• We don’t know what appeared first - the senile signatures or the metabolic failure (although for some without obvious comorbidities the “clock” was already running fast).

What should science test next?

• Randomized trials: can we "rewind" the epigenetic clock through weight loss (diet/exercise/medication) and reduced inflammation?
• The role of visceral fat and sarcopenia (muscle mass) in biological age.
• Multiomics + organ visualization (liver, vessels) for precision mechanisms.
• Effect on offspring (epigenetic heritability in people of reproductive age).

Conclusion

In young adults, long-term obesity is associated with the fact that their cells demonstrate accelerated biological aging - by the epigenetic clock, telomeres and a whole cascade of signals (inflammation, mitostress, hormones/myokines). The duration of excess weight is decisive. The good news is that biological age is plastic: the sooner we reduce inflammation and visceral fat, strengthen muscles, sleep and metabolic control, the higher the chance to slow down the "clock".

Source: Correa-Burrows P., Burrows R., Albala C., et al. Long-Term Obesity and Biological Aging in Young Adults. JAMA Network Open. 2025;8(7):e2520011. Full text available (PMC). doi:10.1001/jamanetworkopen.2025.20011