Calorie restriction reduces biomarkers of cellular senescence in humans

• Published in: Aging cell Vol. 23; no. 2; pp. e14038 - n/a
• Main Authors: Aversa, Zaira, White, Thomas A., Heeren, Amanda A., Hulshizer, Cassondra A., Saul, Dominik, Zhang, Xu, Molina, Anthony J. A., Redman, Leanne M., Martin, Corby K., Racette, Susan B., Huffman, Kim M., Bhapkar, Manjushri, Khosla, Sundeep, Das, Sai Krupa, Fielding, Roger A., Atkinson, Elizabeth J., LeBrasseur, Nathan K.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-02-2024; John Wiley and Sons Inc
• Subjects: Adipose tissue; Aging; Biomarkers; Body mass index; CALERIE; caloric restriction; Calories; Chronic illnesses; Females; inflammation; Insulin resistance; Intervention; Long-term effects; Machine learning; Metabolic rate; Metabolism; Nutrient deficiency; Overweight; Senescence; senescence‐associated secretory phenotype; caloric restriction; inflammation; biomarkers; metabolism; CALERIE; aging; senescence-associated secretory phenotype
• ISSN: 1474-9718; 1474-9726; 1474-9726
• DOI: 10.1111/acel.14038

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young‐to‐middle‐aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging‐related conditions. Using plasma specimens from the Comprehensive Assessment of Long‐term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change in HOMA‐IR and insulin sensitivity index at 12 and 24 months, and the change in resting metabolic rate residual at 12 months. Finally, using adipose tissue RNA‐sequencing data from a subset of participants, we observed a significant reduction in a senescence‐focused gene set in response to CR at both 12 and 24 months compared to baseline. Our results advance the understanding of the effects of CR in humans and further support a link between cellular senescence and metabolic health.
Using samples from the CALERIE™ study, we demonstrate that calorie restriction (CR) significantly reduced the concentrations of several circulating biomarkers of cellular senescence compared to an ad libitum diet. Changes in biomarker concentrations were important predictors of the change in HOMA‐IR and insulin sensitivity index, and the change in resting metabolic rate residual. Using adipose tissue RNA‐sequencing data from a subset of participants, we also observed a significant reduction in a senescence‐focused gene set in response to CR. Our results advance the understanding of the effects of CR in humans and further support a link between cellular senescence and metabolic health.