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AGE meeting June 1-5, 2006 Boston, MA

The American Aging Association was founded by Dr. Denham Harman, who discovered free radicals and proposed the free radical theory of aging. It is the pre-eminent association of physicians and researchers devoted to understanding how aging occurs and how to reduce the painful effects often encountered as people age. I have been a member since 1990. Of the meetings I attend, AGE provides the most useful information on ways that I can age gracefully and research that holds promise to sustain my optimism - which this meeting pointed out is very important in reducing the risk of disability - see below. These are rapid notes, provided to deliver information quickly, not to represent good writing style.

Pre-conference  Calorie Restriction
8 - Dr. GUARENTE - SIR2 Genes and Calorie Restriction
SIRT1 is a key anti-aging gene in mammals.  It is involved in stress, fat loss, insulin, reduced inflammation, and neuronal injury.
Resveratrol increases lifespan 20% in fruit flies, found in red wine.
1020 - LEEUWENBURGH
Need slight caloric restriction to increase exercise motivation in animals.  Exercise increases mean lifespan but not maximal lifespan.  Also, exercise counteracts muscle loss with age.
215pm - HOLLOSZY

Effect of long-term caloric restriction in humans - eating 30% fewer calories while getting complete nutrition for vitamins and minerals


Marker

Caloric restricted

Exercise only

Controls

Body Mass Index

19

22

27

%  body fat

8

12

32

C reactive protein
(inflammation)

0.22 mg/L

0.98 mg/L

2.5 mg/L

Blood Pressure

100/60

125/75

132/82

DHEA

753

731

715

Elderly level of DHEA is normally 300. 
See Scientific American March, 2006, pg. 55 for a good article on caloric restriction in humans.

345pm James JOSEPH - Neuronal function
Brain uses 20% of oxygen in humans, 40-50% when thinking.  Oxidative stress and inflammation are key causes of Alzheimer's and Parkinson's.

Important supplements include Fish oil, curcumin, melatonin, alpha-lipoic acid, acetyl-L-carnitine, vitamins C and E, phenolics/flavanoids, which include anthrocyanins and soy isoflavones that are anticancer agents.  When fed to 19 month old rats, supplements helped enormously
neurogenesis was aided by blueberries and strawberries

CR mimetics under study - Metformin, glipozide, and rozglitazide

SATURDAY
830 - HEKIMI
CLK-1 gene limits aging, necessary to make Coenzyme Q; heterozygotes for CLK-1 are long lived, indicating Coenzyme Q may be hazardous.  Coenzyme Q is a membrane antioxidant cofactor, but can act as a prooxidant in the electron transport chain producing superoxide, a potent free radical.  CONCLUSION: Coenzyme Q may be hazardous.
905 - FINKEL - ROS (reactive oxygen species - free radicals) as signaling species
Phosphotases provide off signals to metabolism at rates 1,000 times faster than on signals from kinases.  Off signals prevent cancer, etc.  ROS inhibit phosphatases
1130 - W. J. EVANS - Exercise
8 weeks of progressive resistance training increased strength by 200% in 90 year old humans.  10 weeks of training gave 300% increase in strength, improved balance, and relief from depression.
Exercise while taking a supplement of vitamin D, vit. E and protein was even better
The Daily Value of protein is not enough for the elderly.
Vitamin D intake is related to muscle speed and ability to stand without support (standup time) in the elderly.  Need 2,000 IU over age 65.
Drug Albuterol improves leva dopa and muscle mass in Parkinson's patients.

Essential amino acids and sucrose are important for patients during bed rest, especially in the elderly.  Evans has Bed Rest and Aging Grant from NIH.  Young people lose 2% of muscle mass during 10 days of bed rest.  Elderly lose 9%.  To prevent sarcopenia, require resistance exercise and essential amino acid supplement.

http://www.jacn.org/cgi/content/abstract/23/suppl_6/601S - Research has indicated that increased dietary protein intake (up to 1.6 g protein · kg–1 · d–1) may enhance the hypertrophic response to resistance exercise. It has also been demonstrated that in very old men and women the use of a protein-calorie supplement was associated with greater strength and muscle mass gains than did the use of placebo.

12 - Benedetta BARTALI, Cornell - Protein and inflammation in elderly sarcopenia
14 million over 65 report disability.
in InCHIANTI study, AJCN 2004, 600 people over 65 followed for 3 years.  If C-reactive protein (inflammation marker) is high, protein intake is proportional to strength with or without disease.
Need 1 or more g protein per day per kg body weight in order to maintain strength.
J Gerontol A Biol Sci Med Sci. 2005 Jun;60(6):760-7. Association between physical activity, physical performance, and inflammatory biomarkers in an elderly population: the InCHIANTI study. Current physical activity practice and performance are associated with inflammatory biomarkers. A significant beneficial association is already observed with light physical activity practice and intermediate performance.

2pm - KLEIN - osteoporosis
50% of women and 20% of men over 50 have an osteoporotic fracture.  Peak bone mass is at age 27, falls sharply at age 75.Now can view 100-500K SNPs at once; know of about 5 million SNPs
230pm - WEAVER - life choices
High intake of linoleic acid [omega-6] causes mesenchymal stem cells to become adipocytes [fat cells] instead of osteoblasts [which make bones], leading to obesity and osteoporosis.


Condition

Deaths/year

Osteoporosis

1.5 million

Heart disease

500,000

Stroke

228,000

Breast cancer

100,000

$18 billion/yr spent on osteoporosis
400 iu vitamin D is insufficient, should be 1,000 IU
With 800 IU vitamin D, women had 49% fewer falls
Estrogen therapy is bad
97.5 mg soy isoflavones / day did not have an effect on bone resorption rates

3pm - BLACK - Alendronate is best bisphosphonate to maintain bone strength and reduce osteoporosis
PTH 1-34 is new drug that rebuilds bones, requires daily injection.

SUNDAY
915am - Peter ELIAS - Age-associated changes in the skin barrier - N-acetyl-cysteine maintains epidermal  stem cells, potential for skin cream to maintain epidermal stem cells if absorbed
11am MCELHANEY JE - Influenza in elderly
1 in 3 over age 70 are permanently disabled as a result of three weeks in hospital.  Need protein supplement with essential amino acids
Flu vaccine reduces heart attack/stroke/cancer deaths; hospitalizations are increased 200% and deaths by 700% due to flu and pneumonia
1130 - MARKO - Vitamin E reverses age decline
LAT is key messenger signaling protein to nucleus causing T-cell proliferation to produce immunity via the flu vaccine.  LAT phosphorylation is necessary in this process.  Process occurs fine in young people so they respond to vaccination.  In elderly, 60% do not respond to vaccine due to LAT dysfunction.  200 IU of vitamin E daily completely restores LAT phosphorylation so vaccine works.

MONDAY - Metabolic Syndrome
815 - BARZILAI -
Metabolic syndrome is not yet a disease, just a syndrome.  The following characteristics tend to happen together for unknown cause:
1. obesity
2. high triglyceride level in blood
3. low HDL - cholesterol
4. High blood pressure over 130/85
5. Elevated fasting  blood glucose levels - indicator for diabetes
If you have 3 of these 5 characteristics, you have metabolic syndrome.  #5, hyperglycemia, is the tip of the iceberg.  All contribute to systemic inflammation.  NHANES data of 2000 indicate 70% of US are now overweight!
Obesity leads to macrophage invasion of adipocytes, where they secrete PAI-1.  That causes fibrinolysis, causing clot formation, leading to thrombosis, causes heart disease and stroke.  Obesity also leads to release of free fatty acids which promote insulin resistance leading to diabetes.
845am - HARRIS -
Highest incidence of risk factors is found in Hispanics.   Blacks have lower triglycerides and higher HDL.  Caucasians have more visceral fat, blacks more abdominal fat.  Both increase risk.  In white women, thigh fat gives protection from syndrome. Syndrome most common in those 60-69 years old - 60% have syndrome.  Health outcomes - 40% have coronary heart disease, 20%have strokes, 70% have cardiovascular disease, diabetes incidence rises 300%, many have sleep apnea.  If waist circumference is more than 102 cm [40 inches], risk of having metabolic syndrome increases 500%.
915 - ORDOVAS - SNPs have substantial effect.  4 million SNPs found thus far, predict 11 million will be discovered.  But genotype is only significant for those who are obese.  Stay thin and genotype does not contribute to metabolic syndrome.

Genetic testing - expensive now, $1-300/panel of SNPs.  But will be inexpensive in the near future.  PLIN-11 SNP can predict your ability to lose weight.
945am - BARDONE
SIRT1, the longevity gene in humans, regulates insulin secretion.  Gene is found in beta cells of pancreas, required for insulin secretion in response  glucose.  Free fatty acids have the opposite effect of glucose.
1000am - WU
Aging upregulates inflammation in adipose tissue.  So if you are thin, you have less adipose tissue, less inflammation, lower risk for cancer, heart disease, diabetes, stroke, Alzheimer's.  There is a 14-fold increase in diabetes from age 44 to age 65.
1030  KITANI - What declines with age?
In 1960, we thought kidney function and cardiac output declined with age. Thought Superoxide dismutase [good antioxidant enzyme] declines in brain and liver
Now we know they do not.
Protein malnutrition lowers liver function.
Curcumin extends lifespan slightly!!
3 functions increase with age: creativity, wisdom, spiritual strength
1115 - Mark SMITH - Alzheimer targets
oxidative stress precedes amyloid plaque by decades.  amyloid appears to protect neurons and might not be cause of Alzheimer's.
Melatonin and curcumin decrease risk of Alzheimer's.

1145am - Jim JOSEPH - dietary interventions for healthy brain
Vitamin C, E, alpha-lipoic acid, carnitine, melatonin, fish oil, fruit phenolics which include flavanoids, anthrocyanins, and flavanols.  Anthrocyanins enter the brain directly.  Avocado and blueberry and strawberry have powerful polyphenolics.  All are anti-inflammatory, especially in the hippocampus that is primary in memory function.

2pm - NELSON = Exercise
For optimal exercise, need:
1. strength training
2. aerobic exercise
3. balance
4. flexibility
5. stretching
For bone and muscles, use machines.  For balance and posture, use free weights.

255 - ROSENBERG [world's expert in (conservative) nutrition] - nutrition and vitamins
Conclusion of May 15-17 NIH conference on multivitamins - The present evidence is insufficient to recommend for or against multivitamins.  Yet 52% of people take them, 38% say they take them for more energy.
One-A-Day was first multivitamin in 1941 from Miles Laboratories, contained only A and D.  Vitamin D decreases with age.  People 50-70 may need somewhat more.  B12 requires stomach acid to digest and absorb it, if taking antacids for stomach be cautious to get enough vitamin B12.
Vitamins deserving special attention in discussion:
AREDS and eye disease
vitamin E contributes to immune system
vitamin D necessary for proper signaling
fish oil useful for cognition
folic acid important for older men and cancer prevention

335 -  GOODWIN - Positive Emotions
Life requires a different skill set to be over 80 years old.  Need to be able to be alone, proactive, contemplative, can't be controlling, courage is necessary, elderly like themselves, feel in control of life, motivated to accomplish tasks, can have negative affect or not.
Being happy, cheerful, optimistic, hopeful, able to enjoy life are important characteristics
Recommends book by Seligman, Authentic Happiness
Research on emotions is skewed.  97% is on negative emotions, only 3% on positive ones.  60% is on depression, 30% is on anxiety.
In 4 question survey of emotions, 25% say they feel great, 25% say they feel bad, 50% in the middle.  Socioeconomic and ethnic factors made no difference in distribution.

HAPPINESS REDUCES RISK OF BECOMING DISABLED


Score - 12 is happiest

% of people

Risk of disability

12

30%

1

7-11

45%

2

6 or less

25%

2.3

Optimists walk faster.  Risk of stroke is reduced 27% in people with a positive attitude.  Blood pressure goes down.  People with a positive attitude are 3times more likely to recover after a stroke, hip fracture, or heart attack.
Happiest people are happy all week, sad people are happiest on weekends.
Happiness is a better health predictor than cholesterol level, blood pressure, or body weight.

Lipid levels change dramatically with age, so fish oil is really important with age.
Melatonin affects gene expression levels, causing 50% of gene expression level changes with age to revert to youthful levels.

END OF MEETING NOTES

 

 

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