Title: Strategies For A Healthy, Longer Life: A Review Of The Current Literature
1Strategies For A Healthy, Longer Life A Review
Of The Current Literature
- Joe D. Goldstrich, MD, FACC, CNS
2Learning Objectives
- Participants will
- Become aware of nutritional measures associated
with longevity. - Become aware of nutritional supplements
associated with a longer life and improved
cognition. - Become aware of current research on hormone
therapies (including growth hormone) for
longevity and improved cognition.
3Hope Drives Antiaging Hype
- Antiaging, longevity, and age-management clinics
and institutes offer benefits that would appear
to the appropriately skeptical eye to be too good
to be true. Some advertisers claim that with
their products or services you can do some or all
of the following - Reverse 2 decades of aging
- Live to be 125 or older
- Give yourself a natural face-lift and body
muscle rejuvenation - Substantially reduce your adipose tissue
- Increase your skin thickness and elasticity
- Increase your lean body mass
- Increase your physical strength and energy
- Editorial CLEVELAND CLINIC JOURNAL OF MEDICINE,
DECEMBER 2006
4Dietary Strategies
- Eat what the centenarians eat
- Restrict calories while maintaining good
nutrition - Dont get too skinny or too fat
5Eat What The Centenarians Eat
- The Blue Zones by Dan Buettner
- They all have an active lifestyle
- Sardinia
- Red wine
- Goats milk and cheese
- Plant based diet with small amounts of red meat
- Loma Linda, CA- Seven Day Adventists
- Nuts
- Vegetarian with an early, light dinner
- Drink plenty of water
6Specific nuts with research that supports
cardiovascular health
- Almonds
- Walnuts
- Peanuts (legume)
- skins
- Macadamia
- Pistachio
- most phytosterols
- Chestnuts
- Pecans
- /- Hazelnuts
7- Okinawa, Japan
- hara hachi bu stop eating when 80 full
- Plant based diet with soy
- Costa Rica
- Hard water calcium in the water
- Largest meal in the morning
- Lightly salted corn tortillas, beans and squash
- Not much meat, some eggs
8- Ikaria, Greece currently being researched
- The Ikarian variation of the Mediterranean Diet
is high in vegetables beans, and low in meat
sugar not much fish, but high in potatoes - Wild Greens
- Herbal Teas
- Goat's milk
9Anatomy of health effects of Mediterranean diet
Greek EPIC prospective cohort study
- CONCLUSION The dominant components of the
Mediterranean diet score as a predictor of lower
mortality are moderate consumption of ethanol,
low consumption of meat and meat products, and
high consumption of vegetables, fruits and nuts,
olive oil, and legumes. - Minimal contributions were found for cereals and
dairy products and for fish and seafood, the
intake of which is low in this population. - BMJ. 2009 Jun 23338
10Caloric Restriction and Longevity
- Calorie-Counting Monkeys Live Longer
- Science News 9 July 2009
- Canto, left, a 27-year-old rhesus monkey, is on a
restricted diet, while Owen, 29, is not.
11Caloric Restriction and Longevity
- Previous caloric restriction studies successful
in mice, rats, worms and yeast - 30 fewer calories than usual vs. free-feeding
- Vitamin and mineral supplements to prevent
malnutrition - Diet was stared in monkeys as they reached young
adulthood (7-14 years old) - Average normal lifespan 27 years max 40
- Leaner diets reduced deterioration of muscle and
brain gray matter, two conditions associated with
aging. - 63 of the calorie-restricted animals are still
alive compared to only 45 of their free-feeding
counterparts - Science. 2009 Jul 10325(5937)201-4
12BMI and Mortality
- Reduction in relative risk of developing major
chronic diseases such as cardiovascular disease,
diabetes, and cancer associated with 4 healthy
lifestyle factors among German adults - never smoking,
- having a body mass index (BMI) lower than 30
(most predictive) - performing at least 3.5 hours per week of
physical activity - following a healthy diet
- Arch Intern Med., 2009 Aug 10/24
- Overall, people who were overweight but not obese
defined as a body mass index of 25 to 29.9
were actually less likely to die than people of
normal weight, defined as a B.M.I. of 18.5 to
24.9. - People who were underweight, with a B.M.I. under
18.5, were more likely to die than those of
average weight. - A little excess weight seems to be protective for
the elderly, who are at greatest risk for dying. - Obesity, 2009 Jun 18
-
13Supplements
14Resveratrol
- BACKGROUND Sirtuin 1-7 (SIRT1-7) are
deacetylases that are dependent on NAD() for
their activity. SIRT1 down-regulates p53
activity, increasing lifespan, cell survival, and
neuroprotection it also deacetylates peroxisome
proliferator-activated receptor-gamma and its
coactivator 1alpha, promoting fat mobilization,
increasing mitochondrial size and number, and
positively regulating insulin secretion. Sirtuins
link nutrient availability and energy metabolism.
Calorie restriction, which increases lifespan and
is beneficial in age-related disorders, activates
sirtuin. Major efforts are thus focused to
developing sirtuin activators. - Expert Opin Ther Pat. 2009 Apr19(4)403-14
15- To date, resveratrol is the most potent natural
compound able to activate SIRT1, mimicking the
positive effect of calorie restriction.
Resveratrol might help in the treatment or
prevention of obesity and in preventing the
aging-related decline in heart function and
neuronal loss. - Resveratrol is found in grape skins (red wine gt
white), red peanut skins, some berries the root
of Polygonum cuspidatum (Japanese Knotweed)
16Potential Benefits of Resveratrol
- Inhibits the proliferation of a variety of human
cancer cell lines, including those from breast,
prostate, stomach, colon, pancreatic, and thyroid
cancers. It is not known whether high intakes of
resveratrol can prevent cancer in humans. - Increases the lifespan of yeast, worms, fruit
flies, fish, and mice fed a high-calorie diet,
but it is not known whether resveratrol will have
similar effects in humans.
17- May be the ingredient in red wine responsible for
many cardiovascular benefits antioxidant,
angiogenic, antihypercholesterolemic,
antidiabetic, and cardioprotection during
myocardial infarction. - Can J Physiol Pharmacol. 2009 Apr87(4)275-86
- Resveratrol, via its antioxidant and
anti-inflammatory properties, has the potential
to inhibit the progression of atherosclerosis by
blocking IL-18 - Am J Physiol Heart Circ Physiol. June 26, 2009
18Potential Downside of Resveratrol
- To replicate the dosages of the mice studies in
humans requires about 400 mg of resveratrol daily
for a 175 pound individual. (a 5 oz glass of red
wine has from 0.3 to less than 2 mg resveratrol) - May help protect the liver in rats on a high fat
diet but increasing oxidative stress on a normal
diet. Food Chem Toxicol. 2009 Jun - There is increasing evidence that resveratrol
exhibits pro-oxidant activity under certain
experimental conditions, causing oxidative DNA
damage that may lead to cell cycle arrest or
apoptosis. Arch Biochem Biophys. 2009 Jun
15486(2)95-102
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20Nutritional Supplements Vitamin D
- Prevalence of vitamin D insufficiency in patients
with Parkinson Disease and Alzheimer Disease.
Arch Neurol. 2008 Oct65(10)1348-52 - Childhood asthma may be a consequence of vitamin
D deficiency. - Curr Opin Allergy Clin Immunol. 2009
Jun9(3)202-7 - The vitamin D receptor agonist elocalcitol
inhibits IL-8-dependent benign prostatic
hyperplasia stromal cell proliferation and
inflammatory response by targeting the RhoA/Rho
kinase and NF-kappaB pathways. Prostate. 2009 Apr
169(5)480-93 - Vitamin D and breast cancer. Ann Epidemiol. 2009
Jul19(7)462-7 - Vitamin D for cancer prevention global
perspective. IBID 468-83 - Dietary vitamin D and cancers of the oral cavity
and esophagus. - Ann Oncol. 2009 Jun 1
- Vitamin D deficiency and chronic lung disease.
- Can Respir J. 2009 May-Jun16(3)75-80
21- Association between serum 25-hydroxyvitamin D
level and upper respiratory tract infection in
the Third National Health and Nutrition
Examination Survey. Arch Intern Med. 2009 Feb
23169(4)384-90 - Association between 25-hydroxyvitamin D levels
and cognitive performance in middle-aged and
older European men. - J Neurol Neurosurg Psychiatry. 2009
Jul80(7)722-9 - Vitamin D, a neuro-immunomodulator Implications
for neurodegenerative and autoimmune diseases.
Psychoneuroendocrinology. 2009 Jun 20 - Does vitamin D reduce the risk of dementia?
- J Alzheimers Dis. 2009 May17(1)151-9
- For a complete list of Vitamin D Research, see
the Vitamin D Council at http//www.vitamindcounc
il.org/
22Vitamin D and Alzheimer's
- 1alpha,25-dihydroxyvitamin D Interacts with
Curcuminoids to Stimulate Amyloid-beta Clearance
by Macrophages of Alzheimer's Disease Patients. J
Alzheimers Dis. 2009 May 11 - There are 2 types of macrophages in Alzheimers
patents. Macrophages typically clear plaques in
healthy patients, but don't do so in Alzheimer's
patients. The researchers found that vitamin D
had strong immunostimulating effects on
amyloid-beta phagocytosis in both of the types of
macrophages in Alzheimer's patients. Curcuminoids
in combination with vitamin D significantly
increased total amyloid-beta uptake compared with
D alone, but only in Type I macrophages.
Curcuminoids enhance the surface binding of
amyloid beta to macrophages, while vitamin D
strongly stimulated the uptake and absorption of
amyloid beta, resulting in a benefit through both
genomic and nongenomic effects.
23Vitamin D and Heart Dicease
- Vitamin D deficiency is associated with increased
occurrence of coronary heart disease,
hypertension, insulin resistance, congestive
heart failure and cardiovascular mortality.
24Vitamin D sufficiency is associated with
- Downregulation of the RAAS and lower BP
- Improved glycemic control
- Improved cardiac muscle function
- Decreased coronary calcification
- Decreased risk for cardiovascular events and
mortality - J Am Soc Nephrol. 2009 May 14
- J Am Coll Cardiol. 2008 Dec 952(24)1949-56
- Am J Med Sci. 2009 Jul338(1)40-4
- Pharmacotherapy. 2009 Jun29(6)691-708
25How much Vitamin D?
- Vieth reviewed the extensive literature
supporting the low likelihood of toxicity of
vitamin D3 at intakes of 20004000 IU/day and
reported that toxicity may be unlikely even at
doses as high as 10,000 IU/day (7). His review
suggests that a serum 25(OH)D target of 60 ng/ mL
(150 nmol/L) may be optimal for most individuals.
Annals of Epidemiology 19 (7) 441-445 (July
2009)
26Other Supplements With Anti-aging Potential
- Multivitamin use and telomere length in women. Am
J Clin Nutr 200989185763. - Vitamin C E also corrolated with telemore
length - Deceleration of Senescence in Normal Human
Fibroblasts by Withanone Extracted From
Ashwagandha Leaves. J Gerontol A Biol Sci Med
Sci. 2009 Jul 8 - Ashwagandha is an Ayurvedic shrub. It increased
the in vitro division potential of normal human
cells that appeared to be mediated by decreased
accumulation of molecular damage, downregulation
of the senescence-specific beta-galactosidase
activity and the senescence marker protein,
p21(WAF-1), protection against oxidative damage,
and induction of proteasomal activity - Dietary antioxidants, such as curcumin,
L-carnitine/acetyl-L-carnitine and carnosine have
recently been demonstrated in vitro to be
neuroprotective. Front Biosci. 2009 Jan
114376-97 - Quercetin effects on VO2max and exercise capacity
- Int J Sport Nutr Exercise Metab 2009
27Anything new on Vitamin E?
- Gamma-tocopherol (GT) supplementation alone and
in combination with alpha-tocopherol (AT) alters
biomarkers of oxidative stress and inflammation
in subjects with metabolic syndrome (MetS) - In MetS subjects, the combination of AT GT
therapy results in significant increases in AT
and GT concentrations as well as their
metabolites in plasma and urine, as well as
significant reductions in hsCRP, urinary
nitrotyrosine, and lipid peroxides. These results
point to the superiority of combined AT GT
supplementation in ameliorating both oxidative
and nitrative stress and inflammation in MetS
subjects - Free Radic Biol Med. 2008 March 15 44(6)
12031208
28Hormones for Longevity and Cognition
- Estrogen Overall, the evidence does not
convincingly support the prescription of early or
late postmenopausal estrogen therapy to preserve
cognitive function or prevent dementia. (breast
cancer) - Semin Reprod Med. 2009 May27(3)275-82
- Testosterone Although bioavailable testosterone
is inversely correlated with cognitive decline
and higher levels of testosterone are associated
with better mental control and long-term verbal
memory, studies of testosterone therapy to
enhance cognition have shown mixed results.
(cholesterol, hematocrit, /- prostate cancer) - CLEVELAND CLINIC JOURNAL OF MEDICINE, DECEMBER
2006
29- Dehydroepiandrosterone (DHEA) Cognitive
dysfunction has been associated with low, normal,
and high DHEA(S) levels. One review discussed
improvement of learning and memory dysfunction
after DHEA supplementation in people with low
DHEAS levels, but another study failed to detect
any significant cognitive effects after DHEA
administration. - CLEVELAND CLINIC JOURNAL OF MEDICINE, DECEMBER
2006
30Growth Hormone (GH)
- Statement by the Growth Hormone Research Society
on the GH/IGF-I Axis in Extending Health Span
"Until future clinical research in this area is
conducted, in particular carefully designed,
long-term studies, using validated outcome
parameters, the clinical use of GH or GHS in
older adults, alone or in combination with
testosterone, cannot be recommended. (carpal
tunnel syndrome, lower-extremity edema, diffuse
arthralgia, and diabetes in more than one third
GH treated individuals) - J Gerontol A Biol Sci Med Sci. 2009 Jul 8
- Editorial by Editor of Archives of Gerontology
Geriatrics "There is no doubt that the Adult
Growth Hormone Deficiency Syndrome (AGHDS) shows
a close similarity with most of the age-dependent
functional losses. It has also been shown that
replacement therapy is beneficial in all aspects
of the AGHD pathology, therefore, we have all the
reasons to consider aging as an AGHD syndrome." - Arch Gerontol Geriatr. 2009 May-Jun48(3)271-5
31Still Gonna Die