Notes from the American Aging Association Meeting of June, 2010
*Growth hormone causes aging. Both IFG1 and GH signaling harmful to longevity. GH- and IFG- are like caloric restriction.
*What is aging? Metabolism causes damage, damage causes pathology. Aging is multifaceted – genes extend life 10x, environment 3x, stochastic events 20x. Key identified factors include ROS, telomeres, inflammation, DNA damage, TOR, Inslin/IGF signaling. Three major causes with additive effects from damage – 1. Insulin/IGF (FOXO factors) 2. caloric restriction (FOXA factors) 3. Reduced function of mitochondria (DVL-1 factors). 70% of death is caused by infection/inflammation; 16-30% by traumatic sepsis; 1-10% by age alone. Squirrel lives 40 yrs, rat lives 3, but same size
*AGE-1 gene in C. elegans extends life 10x. Equivalent gene in humans is HSP1.
TOR pathway controls expression of S6K gene, major cause of inflammation that causes chronic disease. Rapamycin is an anticancer drug in humans that blocks TOR.
Main causes of alzheimers – iron, zinc, copper, (esp in amygdala and hippocampus), bad mitochondria, all relate to ROS. PBT2 is new drug, ionophore vs chelator, pushes Zn and Cu back into neurons so they do not bind to amyloid plaque
*LIFESPAN – Human life expectancy has increased 2.5yrs each decade since 1850.
50% of 21st century births will live past 100. Life expectancy at age 70 rose from 6 to 17 years between 1970-1992. Atherosclerosis begins before birth. Future hazards from global warming – infectious disease, air quality, ozone, insect vectors, ticks. Air pollution causes brain aging; get direct transport of toxins from nose to brain; nanoparticles inhibit neurite growth, DHA is protective. ; risk of obesity is as bad as smoking; by 2030, 1 in 8 will be over 65; by 2013, 20% will be obese
1) Normal life curve people die often when relatively young, some live to near maximum lifespan
2) With antioxidants and exercise, health span extended greatly, most life to near maximum lifespan
3) with CR, maximum lifespan substantially increased, 30-50%
*History of Caloric restriction-reduce calories 30% below ad libitum -
1980-90 – how it works
2000-09 – human trials
10-present – CR mimetics – NIH testing about 4 at a time
Round 1 – aspirin helps healthspan, not lifespan
Round 2 – rapamycin is good for anti-cancer, not heart; moderate exercise increases healthspan, excessive exercise does not
Round 3 – Resveratrol does not extend lifespan
Round 4 – testing green tea, curcumin, oxaloacetate, acarbase that blocks weight gain
*2-deoxyglucose (DG) in clinical trials, blocks ATP production, CR mimetic; 0.4% of diet is effective dose. 0.02% inhibits tumor growth. But trials halted, kills the heart.
*Resveratrol – in mice, mimics CR, reduces cataracts, helps bone, Glaxo bought Sirtis with Resveratrol for $720 million
*New mimetic – manoheptulose – from unripe avocadoes; reduces glycolysis, increases mitochondrial biogenesis; no toxicity
*TELOMERES = Healthy centenariams have longer telomeres; shortening correlates with alzheimers, osteoporosis, ox-LDL causes T-cell senescence, telomeres restore t-cell health
*lipid rafts are key to signaling; vit E improves rafts
*ROS Theory – antioxidants are key only in a stressed environment where ROS occur
*MEchanism of cancer better understood, aspirin helps block cancer
*Size of cortex of thymus shrinks with age, so unable to produce naïve T-cells necessary to fight novel antigens. Size of cortex is 2.5 in control, 4 with vitamin C, 4.5 with N-acetyl cysteine, so supplement substantially preserves ability to fight disease.
*Coenzyme Q is likely to be harmful as supplements, except for users of statins with leg discomfort
*Inflammatory gene IL-6 and CRP overproduced with age
*NEUROGENESIS 1 cup of blueberries per day substantially reduces inflammation, esp. in brain; inflamasome causes inflammation, found esp. in abdominal fat. Blueberries and spirulina improve cognition in old animals; they maintain neurogenesis. Blueberry, Green Tea, vitamin D3, increase neurogenesis; 85% become neurons
*Nutritional interventions for inflammation – wolfberry (CHinese herb for diabetes), curcumin, fish oil, caloric restriction
*Brain trauma- neuroinflammation is key to brain damage; do memory testing for outcome – see blueberry study
*Vitamin D stimulates telomerase
*exercise increases brain neurogenesis
*There are 6 disctinct Cognitive processes: learning and memory; attention; perception; language; psychomotor; executive function.At 600 mg daily dose, error rate for long term memory was reduced 50%.
* INFLAMMATION – Many biomarkers of inflammation-increases in CRP, fibrinogen, factor WIII, cortisol, blood clotting; decreases in DHEAS , IGF. CR increases ghrelin, which decreases inflammation and increases thymus growth
*FRAILTY – combination of weakness, weight loss, exhaustion, slow walking and low physical activity.
*MELATONIN – mice at age 6 mos have 10 pg/ml serum, at 12 mos have only 3, at 27 mos (old) have only 2. Melatonin (3 mg 5x weekly) restores immune function genes to youthful expression levels, restores cortex function, reduces tumors by 60% – accesses brain, not an antioxidant, increases survival rate by 10% over time of expt.
*Phytoestrogens in soy and tofu are very beneficial.
*Testosterone drops with age from 350 to 150. More T decreases inflammation markers CRP, IL6, IL1, TNFa UNKNOWN WHETHER THINKING ABOUT SEX INCREASES T
*Muscles are produced by muscle stem cells/satellite cells. Can grow at any age. Old muscles regenerate poorly because of delta/notch signaling in blood.
Thoreau’s three truths: “that this earth is a garden of delights; that the world crowds round the individual, leaving him no vista, and shuts out the beauty of the earth; and that the wholesome wants of man are few.”