Could the age old search for the 'fountain of youth' be as accessible and simple as cutting down on caloric intake?

Cutting just 25% of calories over 2 years slowed biological aging and improved health for healthy adults, reports a new study in Nature Aging.^[1] The findings provide more evidence that mild long-term calorie restriction can partially reverse molecular damage accumulation underlying age-related disease.  

The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) trial aimed to test effects of calorie restriction (CR), defined as lessening food intake without deprivation of essential nutrients.^[2] CR consistently extends healthspan and lifespan in animal models by slowing metabolic processes and molecular dysfunction.^[3] Researchers speculated similar impacts might benefit humans, protecting against chronic illness.^[4]  

The phase 2 CALERIE trial enrolled 220 healthy, non-obese adults aged 21-50 years old. Participants were randomized to 25% CR or maintain regular eating for 2 years. Adherence was quantified through periodic doubly labeled water analysis, which precisely measures calorie expenditure and intake changes.^[5]

The CR group achieved ~11% average restriction, with some reaching over 20%. They experienced sustained weight loss and broad cardiometabolic improvements, like reduced blood pressure and fasting glucose.^[1] Now researchers analyzed blood cell epigenetic aging measures, which estimate biological decline by profiling DNA methylation patterns.

One measure called DunedinPACE indexes multi-system physiological trajectory, predicting collapse decades before disease onset.^[6] DunedinPACE decreased significantly for the CR group compared to controls, indicating slowed aging pace. However other methylation clocks showed no difference between groups. Still, since modest slowing accumulates exponentially,^[7] even small changes could greatly impact population morbidity.^[8]

The findings demonstrate CR feasibility for Western populations chronically overfed on processed foods yet undernourished. Simple sustained calorie reduction reversed biological age progression in just two years for midlife adults. With epidemic obesity and diabetes, these results should compel policy makers to further evaluate CR's disease prevention and healthspan extension potential.

As risks grow from poor nutrition and sedentary living, CR's restorative effects suggest environmental and behavioral adjustments providing sustainable solutions. Heeding CALERIE's lesson to eat less could help individuals seeking to live longer reach their goal by choosing wiser dietary habits.  

For more information on the benefits of fasting and/or caloric restriction, visit our database on the subject here. For an in-depth masterclass on how to regenerate your body, improve longevity, and incorporate an ancestral dietary approach which is lower in high-calorie, low nutrition carbohydrates, enroll for the Regenerate Yourself Masterclass here. Or, read or listen to the book which inspired it here: REGENERATE: Unlocking Your Body's Radical Resilience Through the New Biology.

References

1. Waziry R, Ryan CP, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging. 2023;3:248-257. https://doi.org/10.1038/s43587-022-00357-y

2. Speakman JR, Mitchell SE. Caloric restriction. Mol Aspects Med. 2011;32(3):159-221. 

3. Anderson RM, Weindruch R. Metabolic reprogramming, caloric restriction and aging. Trends Endocrinol Metab. 2010 Mar;21(3):134-41.

4. Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015 Mar 26;161(1):106-18. 

5. Racette SB, Das SK, Bhapkar M, et al. Approaches for quantifying energy intake and %calorie restriction during calorie restriction interventions in humans: the multicenter CALERIE study. Am J Physiol Endocrinol Metab. 2012;302(5): E441-E448.

6. Belsky DW, Caspi A, et al. Quantification of biological aging in young adults. Proc Natl Acad Sci USA 2015; 112(30):E4104-E4110.

7. Kirkwood TBL. Understanding ageing from an evolutionary perspective. J Internal Med. 2008;263:117-127.

8. Goldman DP, Cutler D, Rowe JW, et al. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Aff. 2013;32:1698-1705.