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Calorie restriction studies
- McCay et al: rats increased MEAN and MAXIMUM lifespans
- Weindruch: tested chordates and invertebrates showing rate of aging lower vs controls
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calorie restriction effects
- 1 tissue integrity PRESERVED
- 2 tumor incidence and severity DELAYED
- 3 carcinogen toxicity REDUCED
- 4 Immuno aging DELAYED
- 5 Age at REPRODUCTIVE maturity DELAYED
- 6 learning ability impairment and loss of proteins in lense of eye DELAYED
- 7 Age at onset of reproductive decline DELAYED
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Physiological response to calorie restriction
- body fat DECLINES
- switching from ad libitum to calorie restricted can increase lifespan significantly even midlife
- calorie restricted to ad libitum early in life shows worse effects than late life
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3 hypotheses to explain calorie restriction on lifespan
- 1. developmental: McCay suggested calorie restriction increases lifespan by DELAYING SEXUAL MATURITY
- 2. fat content: inicreased BODY FAT decreases life expectancy
- 3. metabolic rate: calorie restriction DECREASES metabolism
- 4. also proposal that calorie restriction increases lifespan by decreasing both FREE RADICAL production and COLLAGEN glycation (Kristal & Yu)
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disposable soma and calorie restriction
- r-selected (prodigal): when resources abundant, animals lead to ad libitum feeding to go for MAX reproductive effort
- k-selected (prudent): when resources scarce, animals cal restricted and maximize survival @ cost of reprod.
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toxicity
- related to calorie restriction
- so...started using cal restricted as controls
- found that control mice sacrificed longevity for increase in reproductivity
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metabolic rate with aging
- Richard Cutler: showed correlation to support
- Raymond Pearl: rate of living theory, supported by...
- 1. Homeotherms (warm blooded): environmental manipulations can cause INCREASE in metabolic rate and SHORTENED lifespan in rats in fridge.
- 2. hibernating animals show increased lifespan when allowed to hibernate
- 3. Poikilotherms (cold blooded): allow body to equilibrate to outside temp, so in Dros. and fish when cold temperatures had longer lifespan vs warmer temp.
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Steven Austad with metabolism
- said body size is correlated to metabolic rate and longevitiy.
- With cal. restriction, brain to body weight ratio is gonna be higher
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melatonin and aging
- melatonin secretion by pineal gland associated with DEEP sleep
- when lack of sleep, may lack melatonin
- hibernating animals may increase longevity vs non-hibernators b/c of high melatnonin secretion
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Roger McCarter with exercise and cal restriction
- exercise in housefly: caused DECREASE in lifespan
- Exercise in homeotherms: INCREASE in MEAN lifespan, NOT in maximum lifespan (may be thru collagen glycation, NOT free radical quenching)
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gene therapies
- Orr & Sohal with gene therapy: Increasing superoxide dismutase and catalase gene copy numbers can INCREASE lifespan
- p53 gene into humans showed REGRESSION of tumor cells
- Leptin gene (regulates body fat) may allow for longer lifespan thru cal restriction
- dopamine receptor genes: viral delivery may help patients with Parkinson's
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Melatonin
- Russel Reiter: suggested melatonin as anti-oxidant..and free radical quenching by high melatonin could be how cal. restriction increases lifespan
- may be signal for onset of puberty: when declines during growth spurt in childhood, lowers INHIBITION of GnRH, FSH and LH
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pituitary gland
hypothysectomy resulted in longer lifespan (if removed prior to sex maturity)
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Transplantation
- intrinsic to the TRANSPLANTED tissue: taken from young tissues into old animals
- seen intrinsic to recipient with young ovaries to old, in which old body can't respond to increased estrogen with FSH or LH
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Leading causes of Death in elderly (1990 US stats)
- Cardiovascular diseases
- pneumoniamalignant neoplasms
- obstructed pulmonary disease
- diabetes
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Leading causes of death in adolescents and young adults (US 1990 Stats)
- accidents
- homocides
- suicides
- HIV
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Exercise beneficially influences for age-related parameters
- Vital capacity
- body mass index
- HDL to toal cholesterol ratio
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Growth hormone
- Dan Rudman showed elderly with growth hormone showed: increased bone density, skeletal mass, skin thickness, and hand grip strength
- Systolic BP elevated thou :(
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DHEA
found to increase lifespan of rodents, possibly thru calorie restriction
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Retin-A
- derivative of Vitamin A
- Shown to stimulate cell proliferation and collagen production
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