Strategies For A Healthy, Longer Life: A Review Of The Current Literature

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Strategies For A Healthy, Longer Life A Review
Of The Current Literature

• Joe D. Goldstrich, MD, FACC, CNS

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Learning 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.

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Hope 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

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Dietary Strategies

• Eat what the centenarians eat
• Restrict calories while maintaining good
  nutrition
• Dont get too skinny or too fat

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Eat 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

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Specific nuts with research that supports
cardiovascular health

• Almonds
• Walnuts
• Peanuts (legume)
• skins
• Macadamia
• Pistachio
• most phytosterols
• Chestnuts
• Pecans
• /- Hazelnuts

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• 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

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• 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

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Anatomy 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

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Caloric 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.

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Caloric 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

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BMI 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

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Supplements
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Resveratrol

• 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

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• 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)

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Potential 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.

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• 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

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Potential 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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Nutritional 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

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• 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/

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Vitamin 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.

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Vitamin 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.

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Vitamin 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

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How 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)

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Other 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

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Anything 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

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Hormones 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

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• 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

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Growth 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

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Still Gonna Die