+ All Categories
Home > Documents > Caloric Restriction and Longevity

Caloric Restriction and Longevity

Date post: 24-Feb-2016
Category:
Upload: carys
View: 79 times
Download: 3 times
Share this document with a friend
Description:
Caloric Restriction and Longevity. Lisa Cui, Tin Wing ( Faneu ) Liu, Ayumi Tsurushita November 8, 2011. Outline. Introduction Mouse studies of caloric restriction Human studies of caloric restriction Cautions of caloric restriction Conclusion. Introduction. - PowerPoint PPT Presentation
34
Caloric Restriction and Longevity Lisa Cui, Tin Wing (Faneu) Liu, Ayumi Tsurushita November 8, 2011
Transcript
Page 1: Caloric Restriction and Longevity

Caloric Restriction and LongevityLisa Cui, Tin Wing (Faneu) Liu, Ayumi Tsurushita November 8, 2011

Page 2: Caloric Restriction and Longevity

OutlineIntroduction

Mouse studies of caloric restriction

Human studies of caloric restriction

Cautions of caloric restriction

Conclusion

Page 3: Caloric Restriction and Longevity

IntroductionCaloric restriction (CR)– generally defined as 20-40 % of ad libitum consumption with adequate nutrients

First study on mice was done in the 1930s by McCay et al

Showed an increase in mean and maximal lifespan

Other proposed benefits:Decreased CVD risk, later onset of chronic disease, decreased oxidative damage

Page 4: Caloric Restriction and Longevity

Hypothesis of the Mechanism of CR

Decreased energy expenditure

Decreased body weight

Decreased oxidative stress/free radicals

Hormesis - low levels of stress have positive, potentially life- extending effects

Page 5: Caloric Restriction and Longevity

Rodents Study by Sohal et al.

Oxidative Damage during aging and in response to food restriction in the mouse

Oxidative Damage:Inherent inadequacy of antioxidant defensesOxidative stress: imbalance between oxidant fluxes and antioxidant defenses

Aim: to test the relevance and validity of oxidative stress hypothesis of aging in life span extension by CR

Page 6: Caloric Restriction and Longevity

Rodent Study by Sohal et al.

Study Design59 mice aged 9, 16 or 23 months

Ad libitum (AL) fed mice and CR (40% lower in calories) fed mice

Obtaining data of reduced protein oxidation, O2- and H2O2 production in the brain, heart, and kidney.

Page 7: Caloric Restriction and Longevity
Page 8: Caloric Restriction and Longevity

Rodent Study by Sohal et al.

Results:CR rats exhibited a 43% extension in average life spanMitochondrial oxidants production increases with age = biomarkers of agingProtein Oxidative Damage is associated with aging processCR lessens the damage

Page 9: Caloric Restriction and Longevity

Rodents Study by Masoro et al.

Effect of CR on Age-associated DiseasesMale ad lib. Rats and CR rats (60% intake)Common problem with increasing age in male mice: Chronic NephropathyAd lib. –fed rats had more kidney lesions DR rats were much older at the time of death than the ad. lib-ratsDecrease the contribution of pituitary adenoma to death

Page 10: Caloric Restriction and Longevity

Rodents Studies by Masoro et al. The reduction of dietary energy intake but NOT a

specific dietary component is responsible for the anti-ageing action of CR.

Page 11: Caloric Restriction and Longevity

Summary of results of rodent studies

Increase in mean and maximal lifespan

Decrease in oxidative damage

Later onset of kidney disease

Photo Credit rats image by Olga Barbakadze from Fotolia.com

Page 12: Caloric Restriction and Longevity

Human StudiesPubMed

Biosphere 2

CALERIE studies

Epidemiological Study of population in Okinawa

Page 13: Caloric Restriction and Longevity

Biosphere 2Completely closed, self-sustaining ecological system

Subjects: Four women and four men from the ages 27 to 42 years, and one aged 67 years

Biosphere 2 in Oracle, Arizona

Page 14: Caloric Restriction and Longevity

Biosphere 2Study design:

Diet: low-calorie (1750–2100 kcal/d) vegetables, fruits, nuts, grains, and legumes, with small amounts of dairy, eggs, and meat12% calories from protein, 11% from fat, and 77% from complex carbohydratesdaily vitamin and multivitamin supplements.

Blood samples were drawn from the eight crew members to monitor biological markers.

Page 15: Caloric Restriction and Longevity

Biosphere 2Results:

Decrease in BMI of the men decreased by 19%, and the BMI of the women by 13%. Decrease in fasting blood sugar decreased by 21%Decrease in fasting insulin by 42%Decrease in cholesterol by 30%.Decline in LDL:HDL rati

Page 16: Caloric Restriction and Longevity

Biosphere 2Strength of the study:

Length (2 years)Subjects were humanCalorie closely monitored, and caloric restriction maintained

Weakness of the study:Small sample sizeNo control group Other confounding variables such as the daily physical exercise

Page 17: Caloric Restriction and Longevity

CALERIE Study 1Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals

6 months of calorie restriction

Randomized controlled trial of healthy, sedentary men and women (N=48)

Page 18: Caloric Restriction and Longevity

CALERIE StudyResult:

reduced weight, fat mass, fasting serum insulin levels, and core body temperature in caloric restriction groupscalorie restriction results in a decline in DNA damageNo strong evidence for reduced oxidative damage

Page 19: Caloric Restriction and Longevity

CALERIE StudyCalorie restriction or exercise: effects on coronaryheart disease risk factors. A randomized, controlledtrial

Length: 1-yr

Randomized, controlled trial in middle- aged lean and overweight men and women

Group 1: 20% increase in energy expenditure alone

Group 2: 20% decrease in energy intake alone on metabolic risk factor

Page 20: Caloric Restriction and Longevity

Result:improves CHD risk profile loss of 10% of body weight.reduced triacylglycerolreduced LDL-Cfavorable changes in blood pressure

Page 21: Caloric Restriction and Longevity

CALERIE studyImprovements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial

Sedentary men and women aged 50 – 60 y with a body mass index (kg/m2 ) of 23.5–29.9 were randomly assigned to 1 of 2 weight- loss interventions [12 mo of exercise training (EX group; n = 18) or calorie restriction (CR group; n =18)] or to a healthy lifestyle (HL) control group (n =10).

decrease calorie intake by 16% during the first 3 mo and by 20% during the remaining 9 mo.

improves glucose tolerance and insulin action

Page 22: Caloric Restriction and Longevity

Result:improves glucose toleranceInsulin sensitivity

Page 23: Caloric Restriction and Longevity

Summary of Human Studies

reduced weight, fat mass, fasting serum insulin levels, and core body temperature in caloric restriction groupscalorie restriction results in a decline in DNA damageNo strong evidence for reduced oxidative damageimproves CHD risk profile (TG, LDL-C, BP)loss of 10% of body weight.improves glucose toleranceInsulin sensitivity

Page 24: Caloric Restriction and Longevity

Epidemiological study of the Okinawa population

Life expectancy86.0 years for Okinawan women77.6 years for Okinawan men

Caloric restriction due totraditional Okinawa diet is low in calories but nutritionally dense a result of periodic crop failures and marginal food supply that occurred post WWII until the 1960s

Page 25: Caloric Restriction and Longevity

Epidemiological study of the Okinawa population

Low incidence ofCHDLymphoma, prostate cancer, breast cancer, and colon cancer are remarkably low in age-matched Okinawans versus other Japanese and Americans

life-long low BMI

extended mean and maximum life span

Page 26: Caloric Restriction and Longevity
Page 27: Caloric Restriction and Longevity

Cautions Regarding Calorie Restriction

Bone Loss and Bone Fracture

Decreased Aerobic Capacity

Changes in immune function

Menopause and low estrogen can cause bone loss…but usually it’s much slower and less severe

Page 28: Caloric Restriction and Longevity

CR Induces Bone Loss and Bone Fracture?

Pennington Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Research Team

Subject: young, overweight individuals

Duration: 6 month

Result: 2 of the 3 biomarkers for longevity—fasting insulin concentrations and core body temperature—were reduced with CR

Possible mechanism: significant reductions in fasting concentrations triiodothyronine and leptin

Page 29: Caloric Restriction and Longevity

Reduction in Bone Mineral DensityWashington CALERIE Study

Subject: middle-aged, non-obese adults aged 50 through 60

Duration: 12 months

Results: reduction in bone mineral density (BMD) (approximately 1.5% overall) at the lumbar spine, total hip, femoral neck, and intertrochater was correlated to weight loss in the CR group

Page 30: Caloric Restriction and Longevity

Decreased Aerobic Capacity

Washington University School of Medicine CALERIE

Subject: Healthy 50 to 60 year old nonobese men and women

Duration: 12 months of CR

Results: significant reductions in absolute thigh muscle mass, knee flexor strength, and VO2 max, whereas a similar 1-yr energy deficit induced by exercise completely preserves thigh muscle mass and strength and improves VO2 max.

Page 31: Caloric Restriction and Longevity

Don’t Like Bone Loss and Decreased Aerobic Capacity?

Changes in bone mass and/or turnover are less pronounced when the same energy deficit is achieved by combining CR with structured aerobic exercise

Aerobic classes (step dancing)

Treadmills

Exercise bicycles

Ski machines

Air gliders

Jogging

Page 32: Caloric Restriction and Longevity

ConclusionThere are both benefits and cautions to prolonged caloric restriction

CR may be improved if combined with exercise

Long term studies are necessary to assess relationship between caloric restriction and aging

Page 33: Caloric Restriction and Longevity

ReferenceHeilbronn, L. K., de Jonge, L., Frisard, M. I., DeLany, J. P., Larson-Meyer, D. E., Rood, J., et al. (2006). Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: A randomized controlled trial. JAMA : The Journal of the American Medical Association, 295(13), 1539-1548.

Lefevre, M., Redman, L. M., Heilbronn, L. K., Smith, J. V., Martin, C. K., Rood, J. C., et al. (2009). Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis, 203(1), 206-213.

Masoro, E. J. (1995). McCay's hypothesis: Undernutrition and longevity. The Proceedings of the Nutrition Society, 54(3), 657-664.

Sohal, R. S.; Ku, H. H.; Agarwal, S.; Forster, M. J.; Lal, H. Oxidative damage, mitochondrial oxidant generation and anti- oxidant defense during aging and in response to food restriction in the mouse. Mech. Ageing Dev. 74:121-133; 1994.

Page 34: Caloric Restriction and Longevity

ReferenceTrepanowski, J. F., Canale, R. E., Marshall, K. E., Kabir, M. M., & Bloomer, R. J. (2011). Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: A summary of available findings. Nutrition Journal, 10, 107.

Villareal, D. T., Fontana, L., Weiss, E. P., Racette, S. B., Steger-May, K., Schechtman, K. B., et al. (2006). Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: A randomized controlled trial. Archives of Internal Medicine, 166(22), 2502-2510.

Walford, R. L., Mock, D., Verdery, R., & MacCallum, T. (2002). Calorie restriction in biosphere 2: Alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. The Journals of Gerontology.Series A, Biological Sciences and Medical Sciences, 57(6), B211-24.

Weiss, E. P., Racette, S. B., Villareal, D. T., Fontana, L., Steger-May, K., Schechtman, K. B., et al. (2007). Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss. Journal of Applied Physiology (Bethesda, Md.: 1985), 102(2), 634-640.

Willcox, B. J., Willcox, D. C., Todoriki, H., Fujiyoshi, A., Yano, K., He, Q., et al. (2007). Caloric restriction, the traditional okinawan diet, and healthy aging: The diet of the world's longest-lived people and its potential impact on morbidity and life span. Annals of the New York Academy of Sciences, 1114, 434-455.


Recommended