Aging Interventions

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Aging Interventions

• Altering Aging

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SuperlongevityFact or Fiction ?
Fountain of Youth ??? Anecdotal evidence of
superlongevity Caucasia, Pakistan, Ecuador, over
150 years? rural villages high
altitiude usually men cultural reverence for
age Current Oldest Gertrude Baines Los Angeles,
CA born 1894 (115)
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Anti-Aging Interventions
Experimentally Proven Lab Interventions Caloric
Restriction - Rats
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NP - ad lib (113 Kcal/wk) N/R40 - 40Kcal/wk N/R50
- 50Kcal/wk N/N85 - 85 Kcal/wk N/R50lopro - low
protein 50Kcal/wk
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Calorie Restriction
Healthy or Sick and Feeble ?? Age-Related
Pathologies Delayed Onset Decrease
Inflammation Decreased Endocrine
Hyperplasias Decreased tumors slower
growth Incidence of some cancers increase (live
longer) Decreased Exposure to carcinogens?? Exp
erimental exposure Fewer tumors in calorie
restricted
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Calorie Restriction
Effect on Immune Function ?? Enhanced cell
mediated immunity Decreased Antibody
Production delayed onset of autoimmune diseases
in susceptible strains Delay in Age-Related
Physiological Changes e.g. reproductive
senescence loss of lens crystallin decline in
learning ability
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Calorie Restriction
CR - affects directly or indirectly a fundamental
process(es) involved in regulating biological
aging Physiological Response to CR - amount of
body fat total food or calories eaten decreased
intake of toxins
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Restricted Normal and Restricted Obese - Same
Longevity Despite 3.5X the Body Fat ! Longevity
Related to Food Consumption not body composition
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Caloric Restriction
Developmental Stage - Restricting Calories at
mid life ? Mice at 1 year, restricted to 50 ad
lib live significantly longer
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Caloric Restriction
What is the mechanism ?
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Caloric Restriction
Effects on Metabolism- Lowers Body
Temperature Shift from Fat Synthesis to
Glucose lower than normal met. Rate before
eating higher than normal after
eating decreases metabolic end
products oxidative stress and
damage Increased Metabolic Efficiency lower
blood glucose Reduces Accumulation of AGEs
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Caloric restriction
Evidence in Humans ? NIA study - Weindruch, U.
Wisconsin begun 1987 w/ rhesus monkey long-term
longitudinal study half on 30 calorie
restriction CR have nutrient supplements such
that only calories vary biomarkers immune
system, glucose, insulin, body composition,
metabolic rate
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Normal Reduced Diet Intake
(cal.) 662 488 Body weight (lbs.) 31.5 20.5
Lean Body Mass 21.6 18.9 REE
(BMR) 2.05 1.65 REE/FFM 0.21 0.19 glucose
(mg/dl) 74 53 insulin (uM/ml) 44 10 Leptin
(ng/ml) 5.8 1.0 survivors () 78.3 90
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Humans?

• CR Society
• http//www.cbsnews.com/stories/2005/12/30/eveningn
  ews/main1172297.shtml

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Metabolic Rate
Inverse relationship between Metabolic rate and
Life Span Experimental manipulation of Metabolic
Rate within a species Homeotherms - Rat reared
at 48F increase metabolism to thermoregulate ate
44 more food, but had lower mass no difference
in mortality Poikilotherms - Drosophila life
span increased at low temp.
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Exercise
Rate-of-Living Theory ? Results confounded by
weight loss and/or stunted development when
controlled for exercise increases average life
span BUT no change in max. longevity caloric
restriction exercise, inc. max. longevity
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What can you Do?
Avoid Premature Death Tobacco 400,000
Diet/Exercise 300,000 Alcohol 100,000 Microb
ial 90,000 Toxic Agents 60,000 Firearms 35,00
0 Sexual Behavior 30,000 Motor Vehicles
25,000 Drug Use 20,000 Est. deaths 1990 in
U.S.
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Nutrition in Humans
Caloric Restriction no hard data evidence from
protozoa, spiders, guppies, rodents CR
Society population studies French
(Mediterranean) Paradox high fat diet, high
incidence of smoking, but longer life span low
animal fat (cheese, fish, olive oil) fresh
fruits and vegetables, legumes red
wine Vegetarian Diet- 11 yr longitudinal study
in Germany vegetarian mortality from all causes
½ that of carnivores
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Dietary cancer chemopreventive compounds
LycopeneTomato Lycopersicon esculente, Solanaceae
DaidzeinSoya beans Glycine max, Leguminosae
ResveratrolGrape and red wine Vinca vinifera
CoumestrolSoya beans Glycine max, Leguminosae
SilymarinMilk thistle,Silybum marianum,
Compositae
QuercitrinBlueberryVaccinium myrtillus,
Ericaceae
Folate
Vitamin K1
CurcuminTurmeric Curcuma domestica, Zingiberaceae
SulforaphaneBroccoli, Brasica oleracea Cruciferae
Sinalbin White mustard Sinapis alba, Cruciferae
Sinigrin Black mustard Brassica nigra, Cruciferae
(-)Epigallocatechin-3-O-gallate EGCGGreen
tea Camellia sinensis, Theaceae
Glucobrassicin Horseradish Armoracia rusticana,
Cruciferae
Indole-3-carbinol Cruciferous vegetables Crucifera
e
GenisteinSoya beans Glycine max, Leguminosae
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Human Nutrition
Micronutrients Vitamins and Minerals Antioxidan
ts Vit. C, E, Selenium, Quercetin Resveratrol
Leutein, Lycopene, Beta-Carotene
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NRC Recommendations

• Reduce fat intake to 30 of calories (or less),
  Sat.Fat 10 or less
• 5 or more servings of fruits and vegetables, 6 or
  more complex carbs
• Maintain mederate protein intake
• Balance food intake with exercise to maintain
  approp. Weight
• Limit alcohol to 1 ounce pure alcohol/day (24 oz.
  Beer, 10 oz. Wine)
• Limit salt to 6g or less (1/4 oz.)/day
• Maintain adequate Calcium intake
• Avoid dietary supplements in excess of RDA
• Maintain fluoride intake esp. during tooth
  formation and growth.