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Calorie Restriction Retards the Aging Process

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified October 2012 by MARIA PIA DE LA MAZA, University of Chile.
Recruitment status was:  Recruiting
Information provided by (Responsible Party):
MARIA PIA DE LA MAZA, University of Chile Identifier:
First received: January 6, 2012
Last updated: October 20, 2012
Last verified: October 2012
Calorie restriction is the only experimental manipulation that prolongs longevity in experimental animals. The life prolonging effects of calorie restriction are related to a lower incidence of tumors and less inflammation, but more importantly, a lower generation of reactive oxygen species (ROS). This effect is related to the overexpression of two groups of enzymes. One is a group of (NAD+)‐dependent deacetylases called sirtuins whose main actions are to increase free fatty acid flow from adipose tissue, improve insulin secretion and promote mitochondrial biogenesis in muscle. The other group corresponds to uncoupling proteins (UCP), specially UCP 3 that reduces the mitochondrial production of ROS. On the other hand, an effect of calorie restriction that is always reported, is a decrease in resting energy expenditure. A reduction in the activity of UCP1 in brown adipose tissue could be a mechanisms to explain this effect. However sirtuins apparently increase the expression of UCP1.Recently PET CT scans have emerged as a non invasive methodology to recognize brown adipose tissue activity and indirectly, UCP1 activity. Also measurement of telomere length in peripheral blood mononuclear cells has consolidated as a good marker of aging. Two possible models of calorie restriction can be studied in humans. One is a retrospective model in which adults are separated in those that have maintained a stable weight during adulthood in a manner analogous to the weight clamp model of calorie restriction in non human primates. This model is only reliable if there are objective records of the weight that the studied subjects had 20 or more years ago. In the retrospective part of this project the investigators propose to study adults whose weight was recorded previously. The investigators pretend to compare telomere length and expression of SIRT1 and 6 in PBMC, plasma 8 isoprostanes and carotid intima media thickness between weight maintainers and weight gainers. The investigators hypothesis is that weight maintainers will have a better aging profile than weight gainers. In the prospective part of the project the investigators will study a human model of calorie restriction prescribing a 25% reduction in calorie intake during 3 months and comparing groups according to weight loss. At baseline and the end of the study period, UCP3 and SIRT1 expression in muscle biopsies, SIRT1 and 6 expression in PBMC and brown adipose activity, assessed by 18fluorodeoxyglucose uptake using PET/CT will measured. The investigators hypothesis is that individuals subjected to calorie restriction will experience an increase in the expression of UCP3, SIRT1 and SIRT6 and a reduction in brown adipose tissue activity. Simultaneously, these subjects will experience a reduction in oxidative stress markers in muscle and plasma.

Condition Intervention
Obesity Behavioral: energy restricted mediterranean-type diet Behavioral: 25 % calorie restriction

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Calorie Restriction Retards the Aging Process by Inducing Sirtuins and Uncoupling Protein 3, Thereby Reducing the Production of Reactive Oxygen Species.

Further study details as provided by MARIA PIA DE LA MAZA, University of Chile:

Primary Outcome Measures:
  • UCP3 mRNA expression in vastus lateralis after energy restriction [ Time Frame: 3 months ]
    The main outcome measure will be UCP3 mRNA expression in vastus lateralis, which will be measured before and after the 3 month intervention period. This enzyme is the last link in the chain of events that occur after calorie restriction. Millet et al reported a value for UCP3 mRNA of 15 ± 1.5 amol/ìg total RNA in 18 subjects. Expecting a 60% increase over baseline in the expression of the enzyme, 17 subjects per group are required to obtain results with an á of 0.05 and a power of 0.8. Considering attrition rates, we must study 24 subjects per group.

Secondary Outcome Measures:
  • Brown adipose tissue (BAT) activity, indicating UCP1 expression after calorie restriction [ Time Frame: 3 months ]
    Active BAT and its activation with cold exposure in humans, was demonstrated measuring 18 fluorodeoxyglucose uptake using PET‐CT and colocalized the areas of 18F‐FDG uptake to the expression of UCP1 thus for practical purposes it is a non invasive and reliable method to detect the presence of the tissue and the activity of UPC1, whic is downregulated by energy restriction.

Estimated Enrollment: 48
Study Start Date: May 2012
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Calorie restricted
25 % calorie restriction respect measured total energy expenditure, using a Mediterranean diet
Behavioral: energy restricted mediterranean-type diet
Prescription of diet 25 % lower than actual total energy expenditure in overweight or moderately obese premenopausal women
Other Names:
  • Calorie restriction
  • Energy restriction
  • Mediterranean diet
Behavioral: 25 % calorie restriction
25 % calorie restriction respect total energy expenditure

  Show Detailed Description


Ages Eligible for Study:   25 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • overweight or obese premenopausal women aged 25 - 40 years

Exclusion Criteria:

  • diabetes,
  • chronic diseases,
  • extreme physical exercise,
  • drugs affecting energy expenditure
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01508091

Contact: Maria Pia de la Maza, MD 5629781502
Contact: Daniel Carlos Bunout, MD 5629781495

Clinica Alemana de Santiago Recruiting
Santiago, Region Metropolitana, Chile
Contact: Pablo Lavados, MD   
Contact: Claudio Mizon, MD    56996321586   
Sub-Investigator: Claudio Mizon, MD         
Sponsors and Collaborators
University of Chile
  More Information

Responsible Party: MARIA PIA DE LA MAZA, MD, University of Chile Identifier: NCT01508091     History of Changes
Other Study ID Numbers: FONDECYT 1110035
Study First Received: January 6, 2012
Last Updated: October 20, 2012

Keywords provided by MARIA PIA DE LA MAZA, University of Chile:
ageing processed this record on September 18, 2017