Does Obesity Speed Up Aging and Does Calorie Deficit Slow It Down? New Evidence and Rethinking Old Dogma

While some scientists are looking for the "secret of longevity" in calorie restriction, others show that long-term obesity pushes the aging clock much more strongly. JAMA Network Open published a commentary by Antonello Lorenzini, who carefully lays out on the shelves what we know for sure about the effect of calorie restriction (CR) and do not know about humans, and how this picture is changed by new studies - for example, a study from Chile on biomarkers of aging in 28-31-year-olds with long-term obesity.

The author reminds us that in animal models, CR consistently slows down aging, but for humans there is no direct evidence of “an increase in life years” yet – and here the discussion rests on methodology, safety and the difference between reasonable calorie restriction without deficits and malnutrition, which, on the contrary, accelerates the decline of functions. The tone of the commentary is conciliatory: it is worth arguing less about “who is right”, and looking more at the trajectories of body weight throughout life and how long years of obesity “rebuild” the body at the molecular level.

Background of the study

The idea of “slowing down aging” through calorie restriction (CR) comes from the biology of aging: in yeast, worms, flies, and mice, a sustained reduction in energy intake without protein and micronutrient deficiency prolongs life and delays age-related diseases. In humans, the evidence is more modest: CR improves cardiometabolic markers (insulin resistance, blood pressure, lipids, inflammation), but there is little direct data on life extension and long-term safety. At the same time, there is a risk of “going too far”: excessive calorie restriction threatens muscle and bone loss, nutrient deficiencies, menstrual cycle and mood disorders - especially in the elderly, where muscle preservation is critical for longevity.

In parallel, it has become clear in recent years that the “downside” of energy balance – long-term obesity – can accelerate biological aging more than the theoretical benefits of moderate CR slow it down. Ectopic fat and macrophages that support chronic low-symptom inflammation (“inflammaging”) accumulate in adipose tissue, IL-6/CRP levels increase, insulin sensitivity and IGF-1/insulin signals change, oxidative stress and mitochondrial dysfunction increase. The earlier excess weight begins and the longer it persists, the greater the “area under the curve” of metabolic load – and the more pronounced the shifts in biomarker panels, epigenetic “clocks” and clinical risks by young adulthood.

It is against this background that the current debate is unfolding. On the one hand, CR in humans is a potential tool for improving health, requiring personalization (adequate protein, strength training to protect muscles/bones, micronutrient control). On the other hand, for population “anti-aging,” the key is the prevention of long-term obesity from childhood/adolescence: healthy weight, exercise, sleep, stress management, and nutrition with an emphasis on whole foods, fiber, and omega-3. Modern cohort studies with “signs of aging” panels complete the picture: they do not prove causality, but they show that long-term exposure to excess energy leaves a molecular trace of premature physiological decline by the age of 30. As a result, the focus shifts from the debate on “how many calories to cut” to a more pragmatic question: how to prevent

What exactly is being discussed in the comment?

• CR as an idea and as a practice. In invertebrates and rodents, energy restriction without nutrient deficiency slows the signs of aging; in humans, the evidence base is softer and more heterogeneous, but CR consistently improves a range of cardiometabolic parameters. The question of “cost” is the risk of muscle loss, bone density, and nutrient deficiencies with excessive dietary restriction.
• The role of obesity. There is growing evidence that it is the duration of obesity (and not just the fact of excess weight) that is associated with the "signature" of premature aging - inflammatory and hormonal markers, metabolic disorders, shortening of telomeres, etc.
• Author's conclusion: Shift the focus from "CR as a panacea" to prevention of chronic excess energy and excess weight from an early age; in the clinic - individualize calorie reduction so as not to harm muscles and bones, especially in the elderly.

At the same time, the same issue of the journal published a paper by a Chilean group (Santiago Longitudinal Study), which became an important context for the discussion: in young adults aged 28-31, long-term obesity "since adolescence" and especially "since childhood" turned out to be associated with a pronounced shift in a whole set of biomarkers related to "signs of aging". This is not about wrinkles - it is about molecular signals and systemic processes.

What the Chilean study showed (briefly about the design and results)

• Comparison subjects: 205 cohort participants:
  - normal BMI trajectory (healthy weight throughout life) - 43%;
  - persistent obesity since adolescence - 21%;
  - persistent obesity since childhood - 36%. Average “duration” of obesity - ≈13 and ≈27 years in groups 2 and 3.
• What was measured: a panel of biomarkers reflecting “antagonistic” and “integrative” signs of aging: highly sensitive CRP, IL-6, FGF-21, IGF-1/IGF-2, apelin, irisin, etc.
• What they found: Long-term obesity was associated with a more unfavorable profile of these markers by age 30; the effect was large in magnitude. The authors are cautious in their conclusion: the data point to a “premature physiological decline” in long-term obesity.

It’s important to understand the boundaries: the Chilean study is not an RCT, and it’s not “measuring aging in years.” These are biomarkers, not clinical events, and the design (a nested case-control study) doesn’t prove causality. But it fits in well with the logic of the JAMA Network Open commentary: even if CR is a useful tool in individual groups, the most reliable “anti-aging” for a population is to avoid long-term obesity.

What does this mean in practice?

• Start early and gently. Childhood and adolescence are “windows” when it is easier to prevent a trajectory of persistent obesity than to correct it later for decades.
• Individualize calorie restriction. Reduce energy - only without protein/micronutrient deficiencies, with muscle and bone tissue protection; especially carefully - in the elderly.
• Look beyond calories. Sleep, stress, activity, diet quality (fiber, fish, vegetables, whole grains) are factors that change "biological age" no worse than a calorie counter.
• Don't confuse CR with starvation. "Less is younger" doesn't work: undernourishment accelerates loss of function. Balance is more important than extremes.

Limitations and what to check next

• Commentary is an Opinion/Commentary, not a meta-analysis: it provides a framework for debate and priorities, but does not replace direct human testing with "hard" outcomes.
• More longitudinal data is needed on biomarkers: to what extent do early “signatures” really predict disease and mortality?
• CR in humans requires clear safety protocols (muscle/bone preservation) and 'response' criteria - possibly using panels of aging biomarkers.

Summary

The “CR slows aging” vs. “obesity speeds up” debate in 2025 leans toward pragmatism: avoiding long-term obesity is more important than chasing extreme calorie deficits; and if you restrict, do it smartly, safely, and personally.

Source: Lorenzini A. Calorie Restriction, Obesity, and the Aging Process. JAMA Network Open. 2025 Jul 1; 8(7):e2522387. doi:10.1001/jamanetworkopen.2025.22387