Lecture 24: Biology of Ageing Part II PDF

BIOLOGY OF AGEING PART II LECTURE 24 Learning Objectives  Describe nutritional intervention for lifespan extension  Discuss nutrients of concern for this age group Food Matters: Nutrition Contributes to Long & Healthy Life Cumulative effects of lifelong dietary habits determine nutrition...

BIOLOGY OF AGEING PART II LECTURE 24 Learning Objectives  Describe nutritional intervention for lifespan extension  Discuss nutrients of concern for this age group Food Matters: Nutrition Contributes to Long & Healthy Life Cumulative effects of lifelong dietary habits determine nutritional status in old age CDC suggest that longevity depends on: 10% __________________ access to health care 19% __________________ genetics 20% __________________ environment 51% __________________ lifestyle How can we extend lifespan? Calorie Restriction - Only non-genetic manipulation that extends lifespan - Maintain proper nutrient intakes Supported by studies in: Mice Rats Flies (drysophila) Dogs Worms (c. elegans) Calorie Restriction for Longevity 30-40% fewer calories vs. full fed mice (6 wks) Extends life span in rodents Modified from Weindruch R et al. J Nutr. 1986 Calorie Restriction for Longevity Start at 1 month Start at 1 year Later the restriction starts in life, lower the life extension in mice Modified from Weindruch R et al. J Nutr. Calorie Restriction in Non-Human Primates Lifespan of rhesus monkey ~27 yrs Study published in 2017 (30% CR) ↓ blood pressure, body temperature, insulin sensitivity ↓ plasma lipids, ↓ incidence of cancer Can be influenced by: - Diet, nutrient composition - Intakes - Genetic background Can Calorie Restriction Extend Human Life? If a 48 yr old male (BMI 20-25) started CR at 30% reduction (2500 kcal to 1750 kcal) and sustained CR for next 30 yrs to the current life expectancy of 78 yr, he would derive a life extension of ~2.8 yrs. What if he waited until he was 55 yrs to start CR at 30% and continued for 23 yrs? He would derive a life extension of 6 wks. Speakman and Humbly (J Nutr 2007:137:1076-86.) What is the takeaway? Calorie Restriction in Humans Centenarians from Okinawa: epidemiological evidence - Low caloric intake in school children - ~10-15% energy deficit from youth to middle-age - Nutrient dense diet - Laborious occupations/daily activities 20% CR in adults residing in Redman. Antioxid Redox Signal. 2011 Okinawa vs mainland Calorie Restriction in Humans – Biosphere study -750 kcal/d unexpected CR during 6 months Confinement inside Percentage change in Biosphere body weight (%) ↓15% Improvements in : Heart Disease Risk measures Total Cholesterol High Density Lipoproteins Low density Lipoproteins Triglyceride Systolic/Diastolic BP 10-15% weight loss Glucose Core temperature Metabolic rate  Calorie Restriction in Humans CALERIE study (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) Prospective, randomized control 2 yr 25% CR (vs ad lib) Non-obese healthy adults Aged 25-45 yr decreased systemic oxidative stress Calorie Restriction in Humans Limitations Practical? 30-40% impractical; 10-15% more feasible Adverse effects - Lack of concentration, amenorrhea Genetic variability in longevity and in response to CR Endpoints? - Biomarkers - Death Will likely never determine effect of CR on lifespan in humans Focus on quality of life? Increased health span? Nutrients of Concern MICRONUTRIENT INTAKES Nutrients of Concern: Age Associated Vitamin A  Plasma levels & liver stores ↑ with age  ↓ clearance from the blood  Vulnerable to toxicity & possible liver damage than deficiency  UL: 3000 mcg  Beta-carotene will not damage the liver Vitamin D, Calciferol  Decreased ability of skin to synthesize Vitamin D  Limited sunlight exposure (institutionalized, winter, clothing, sunscreen)  Medication Nutrients of Concern: Low Dietary Intake Potassium  Major electrolyte; Na+ and K+ control water balance  Adequate intakes can offset negative effects of Na+ intake  Fruits and vegetables excellent sources- DASH diet Vitamin K  Blood coagulation, bone health – Vitamin K  Nutrients of Concern: Low Intake Vitamin B12  Despite adequate intake, have lower serum B12 levels  Bacterial growth of stomach → ↑inflammation and ↓hydrochloric acid & pepsin (from atrophic gastritis) = inability to split B12 from protein carriers  Synthetic or purified B12 is not protein bound and is much better absorbed Fluid  Body water ↓ with age= smaller margin of safety for staying hydrated  Fluid recommendations, 1 mL of fluid/kcal consumed, with a minimum of 1500 mL Summary  Aging is related to changes in cellular structure and metabolic disruption Better way to define old age is by functional status, than chronological status Several physiological changes accompany old age There are multiple theories of aging, but they are theories Calorie restriction can be an effective strategy to reduce age related decline – for animals and humans both