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RESEARCH PAPER / 2026-02-04

Substrate Utilization During Short-Term Fasting in Older Men and Women.

San Wang, Rita H Tsay, Danya Zhang, Naomi K Fukagawa

Laboratory of Human Nutrition and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA.Laboratory of Human Nutrition and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA. · pubmed

Abstract

Older people are prone to involuntary fasting, but systematic assessment of their mobilization and oxidation of the three macronutrients during fasting has not been previously reported. Because of changes in body composition and metabolic regulatory pathways with aging, older people might have different kinetics of utilization of macronutrient stores during fasting than younger people. We measured body composition by dual-energy X-ray absorptiometry and studied the effects of a 36-hour fast on protein mobilization, lipolysis, glucose output, and protein, fat, and carbohydrate oxidation in 10 older (60-81 y) and 10 younger (18-35 y) healthy adults. A 36-hour fast induced a pronounced shift toward fat oxidation: in the postabsorptive state fat oxidation averaged 52-55% of resting energy expenditure (REE) and increased to 63-68% after fasting, with corresponding decreases in carbohydrate oxidation. Protein oxidation decreased with fasting but still contributed 16-18% of REE in older participants. For several metabolic variables (respiratory exchange ratio, glucose Ra, glycerol Ra, urea Ra, urea excretion, and percent of REE from carbohydrate and fat), we observed significant age×fasting interactions (P < 0.01). Younger adults exhibited larger decreases in glucose Ra and greater increases in markers of protein turnover (leucine Ra, urea production) and lipolysis, whereas older adults showed blunted glucose and leucine responses but maintained substantial protein oxidation. These age-related differences suggest that older adults rely relatively more on ongoing protein catabolism during short-term fasting, which may contribute to vulnerability to muscle loss during illness or prolonged inadequate intake.

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Research summary

Older adults exhibit different macronutrient oxidation patterns during short-term fasting compared to younger adults. This study provides insights into metabolic changes in aging, which could inform strategies to mitigate age-related muscle loss and improve healthspan.

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