Calorie Restriction Retards the Aging Process

NCT01508091 | Unknown

• 1 other identifier: FONDECYT 1110035
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity

Keywords

Obesity; ageing

Outcome Measures

Primary Outcomes (1)

• UCP3 mRNA expression in vastus lateralis after energy restriction

  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.

  3 months

Secondary Outcomes (1)

• Brown adipose tissue (BAT) activity, indicating UCP1 expression after calorie restriction

  3 months

Study Arms (1)

Calorie restricted

EXPERIMENTAL

25 % calorie restriction respect measured total energy expenditure, using a Mediterranean diet

Behavioral: energy restricted mediterranean-type diet; Behavioral: 25 % calorie restriction

Interventions

energy restricted mediterranean-type diet BEHAVIORAL

Prescription of diet 25 % lower than actual total energy expenditure in overweight or moderately obese premenopausal women

Also known as: Calorie restriction, Energy restriction, Mediterranean diet

Calorie restricted

25 % calorie restriction BEHAVIORAL

25 % calorie restriction respect total energy expenditure

Calorie restricted

Eligibility Criteria

• Age: 25 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• overweight or obese premenopausal women aged 25 - 40 years

You may not qualify if:

• diabetes,
• chronic diseases,
• extreme physical exercise,
• drugs affecting energy expenditure

Sponsors & Collaborators

• University of Chile: lead

Study Sites (1)

Clinica Alemana de Santiago

Santiago, Santiago Metropolitan, Chile

RECRUITING

MeSH Terms

Conditions

Obesity

Interventions

Caloric Restriction; Diet, Mediterranean

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet, Plant-Based

Central Study Contacts

Maria Pia de la Maza, MD

CONTACT

5629781502; mpmaza@inta.uchile.cl

Daniel Carlos Bunout, MD

CONTACT

5629781495; dbunout@inta.uchile.cl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 6, 2012
• First Posted: January 11, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: June 1, 2013
• Last Updated: October 23, 2012

Record last verified: 2012-10

Locations

CL (1)