Skin & Muscle

Caloric Restriction Preserves Muscle Strength Despite Muscle Loss: National Institute on Aging

National Institute on Aging (NIA) researchers show that cutting 12% of calories from the diet over two years results in weight loss, preserved strength, and stimulation of longevity genes.

By Bennett M. Sherman

Key Points:

  • Participants who lowered calorie intake by ~12% over two years showed a 10.4% loss in weight that stabilized after the first year.
  • While muscle mass significantly declined in these participants, they maintained their muscle strength, suggesting improved muscle quality.
  • Calorie restriction was associated with improving mitochondria and reducing inflammation.

Cutting daily dietary calories (calorie restriction) has been shown to increase the lifespan and length of disease-free life (healthspan) in organisms from yeast to non-human primates. Human studies have shown that calorie restriction improves healthspan-related parameters such as enhanced metabolism and reduced inflammation.  However, whether calorie restriction improves healthspan and lifespan via the same cellular pathways in humans and animal models remains unexplored. This is important, because if calorie restriction’s effects on human cellular pathways are similar, findings from calorie reduction studies involving animal models likely have more application to humans.

Now, published in Aging Cell, Ferrucci and colleagues from the NIA show that calorie restriction over a two-year period confers a sustained body weight reduction of 10.4%. Furthermore, while those who underwent calorie restriction lost muscle mass, muscle strength was preserved, suggesting enhanced muscle quality. The researchers also found increased gene activity for longevity-related cellular processes like mitochondrial generation along with reduced gene activity for inflammation, similar to gene pathway profiles in calorie restricted animal models. These findings support that human calorie restriction promotes healthspan, and possibly lifespan, in ways similar to animal models.

“A 12% reduction in calorie intake is very modest,” said study author and NIA Scientific Director Luigi Ferrucci, MD, PhD, in a press release. “This kind of small reduction in calorie intake is doable and may make a big difference in your health.”

Cutting Calories Lowers Weight and Stimulates Longevity Genes

To confirm the prospective weight loss-related benefits of calorie restriction, Ferrucci and colleagues measured the body weight changes of 19 young and middle-aged study participants in the Comprehensive Assessment of Long Term Effects of Reducing Intake of Energy (CALERIE) study. These adults went through a ~12% restriction in dietary calorie intake over a two-year period. The researchers found that body weight significantly declined over the first 12 months of the dietary intervention and then stabilized over the second twelve-month period. These findings confirm that even a modest calorie intake reduction of ~12% can substantially lower one’s body weight, which is sustained thereafter.

(Das et al., 2023 | Aging Cell) Calorie-restricted adults exhibit significantly lowered body weight over the first year that stabilizes thereafter. In calorie-restricted adults (CR), body weight (Weight [Kg]) declines after 12 months (12mo) and remains stable through 24 months (24mo). Adults who eat a standard diet (AL) display no such weight loss.

Since weight loss is typically associated with muscle loss, Ferrucci and colleagues measured muscle mass in those who’d undergone calorie restriction for two years. While muscle mass significantly declined in the study participants, they interestingly exhibited preserved muscle strength as shown with a knee extension force measurement. These results show that while muscle mass declines with a calorie restricted diet, muscle strength is preserved, suggesting enhanced muscle quality.

(Das et al., 2023 | Aging Cell) Calorie-restricted adults show reduced muscle mass but preserved muscle strength. Left) Calorie-restricted adults (CR) exhibit significantly reduced muscle mass (DeltaMass) after two years of the dietary intervention. Right) A knee extension force measurement shows that calorie-restricted adults (CR) don’t have reduced muscle strength (Muscle strength [N.m]) compared to adults who eat a standard diet (AL).

To gain a better understanding of the cellular pathways facilitating enhanced muscle performance, the NIA researchers performed muscle biopsies on 90 study participants — 57 who underwent calorie restriction and 33 who ate a standard diet. Following the biopsies, Ferrucci and colleagues measured the abundance of mRNA, precursor molecules for protein synthesis, to measure gene activity related to multiple longevity-related pathways.

They found that calorie restriction enhanced gene activity for numerous pro-longevity pathways like mitochondrial production and autophagy — the cell’s waste disposal process. At the same time, calorie restriction reduced activity for genes related to inflammation. These gene activity modulations relate to pathways altered in animal models that undergo calorie restriction. As such, these data support the potential for calorie restriction studies in animals like rodents and non-human primates applying to humans.

Cutting the Optimal Quantity of Calories

With studies done in rodents, calorie restriction has been shown to extend lifespan by 35% to 65%, depending on the quantity of calories cut from the diet. Moreover, a study done in non-human primates showed that a calorie-restricted diet extends lifespan modestly but still significantly. Along those lines, by showing that calorie restriction modulates the activity of pro-longevity genes in humans related to pathways influenced in animal models, the possibility that a calorie-restricted diet may extend lifespan in humans remains. These findings may hold more promise for those who consume a high-fat and sugar-loaded Western diet since such a diet increases the likelihood of age-related heart disease.

Another study utilizing data from the CALERIE participants showed that a calorie-restricted diet slows the pace of biological aging and reduces mortality risk. As such, a slower pace of aging and reduced mortality risk may confer lifespan extension. However, more research is needed to confirm this.

With calorie restriction’s beneficial effects on body weight and modulation of longevity genes, researchers need to identify the optimal quantity of calories to cut from the diet. It’s possible that certain people, like those who have particular age-related diseases, would benefit from cutting more than 12% of calories from their diet to potentially enhance calorie restriction’s benefits. Moreover, researchers haven’t determined how much calorie restriction people can undergo before experiencing intolerable discomfort. More research needs to be done to address these issues.

Model and Dosage

Model: Young and middle-aged nonobese adults included in the CALERIE study

Dosage: Reducing calorie intake by ~12% over a two-year period


Das, J. K. et al. Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study. Aging Cell e13963 (2023) doi:10.1111/acel.13963.


López-Lluch, G. & Navas, P. Calorie restriction as an intervention in ageing. J Physiol 594, 2043–2060 (2016).


Mattison, J. A. et al. Caloric restriction improves health and survival of rhesus monkeys. Nat Commun 8, 14063 (2017).


Oikonomou, E. et al. Western Dietary Pattern Is Associated With Severe Coronary Artery Disease. Angiology 69, 339–346 (2018).


Weindruch, R. The retardation of aging by caloric restriction: studies in rodents and primates. Toxicol Pathol 24, 742–745 (1996).


Waziry, R. et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nat Aging 3, 248–257 (2023).

To The Top