Evidence-Based Nutritional

Strategies For The Aging Brain

Michael Lara, MD
Diplomate, American Board of Psychiatry and Neurology
Diplomate, American Board of Psychiatry and Neurology
Michael E. Lara, MD
! www.DrMikeLara.com
! Email: mlaramd@gmail.com
! Facebook: www.facebook.com/BrainMD
! Twitter: @MichaelLaraMD
2
$30 Billion
Estimated amount of money Americans spent
on health supplements in 2012
Nutrients from healthy food sources or from supplements?
Which Would You Choose?
4
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and Exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and Exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Psychological stress leads to inammatory, oxidative, and
metabolic stress
Chronic Stress Leads to Premature Aging
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High-stressed caregivers age prematurely
Telomere Length and Telomerase Activity
Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004). Accelerated telomere shortening in
response to life stress. Proceedings of the National Academy of Sciences of the United States of America, 101(49), 17312-17315.
High-Stressed
group had aged the
equivalent of 9-17
additional years
Healthy aging, mild cognitive impairment, and Alzheimers
Age-Related Memory Loss vs MCI
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Sleep becomes more fragmented and less restorative as we age
Sleep Changes in the Aging Brain
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Younger Subject
Older Subject
Nearly 50% of older adults have insomnia, and most do not
meet RDA for magnesium intake
Magnesium
! Supplemental magnesium decreases sleep latency,
improves sleep efciency, and increases total sleep time
in elderly.
! Magnesium is a glutamate (NMDA) antagonist and GABA
agonist.
! For mild insomnia: 400-800 mg/night of magnesium
aspartate, citrate, lactate or chloride
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Derived from plant Valeriana ofcinalis, valerian is a common folk
treatment for insomnia.
Valerian
! A GABA agonist, valerian may improve sleep quality
and latency, but a 2010 meta-analysis showed only
subjective improvements in insomnia
! 450 mg of valerian extract (0.8% valerenic acid) one
hour before bedtime.
! Doses larger than 450 mg may cause vivid dreams
and morning grogginess
! Long-term use may cause withdrawal symptoms on
abrupt cessation
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Melatonin
! Results of 2013 meta-analysis: May reduce
sleep latency, sleep quality, and improve
overall sleep quality but effects are
modest
! Strongest evidence is for insomnia
associated with circadian rhythm
disorders (shift work sleep disorder and
jet lag)
! Dose range: between 0.3 mg and 3 mg 30
minutes before bedtime
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Efcacy of Melatonin in Increasing Total sleep Time
Ferracioli-Oda E, Qawasmi A, Bloch MH (2013) Meta-Analysis: Melatonin for the Treatment of Primary Sleep
Disorders. PLoS ONE 8(5): e63773. doi:10.1371/journal.pone.0063773
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063773
Mean Difference: 8.48 minutes
PET imaging of !-amyloid
Anatomical Changes in the Aging Brain
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AD
MCI
Control
Small, G. W., Kepe, V., Ercoli, L. M., Siddarth, P., Bookheimer, S. Y., Miller, K. J., ... & Barrio, J. R. (2006). PET of brain amyloid and tau in
mild cognitive impairment. New England Journal of Medicine, 355(25), 2652-2663.
Characterized by cortical and hippocampal atrophy, and
enlargement of ventricles
Pathologic Changes in the Aging Brain
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Age-associated reductions in receptor binding and signaling
Neurotransmitters and The Aging Brain
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Cognitive
Function
Serotonin
Norepinephrine
Dopamine
! Serotonin associated
with sleep, appetite, and
mood
! Norepinephrine
regulates attention and
concentration
! Dopamine associated
with pleasure and reward
Neurotransmitters
Changes in neurotransmitter synthesis, release, binding and
reuptake with normal aging
The Synapse
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The major inhibitory and excitatory neurotransmitters
GABA and Glutamate
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Glutamate
GABA
! Major inhibitory
neurotransmitter in
CNS
! Target of anti-
anxiety and anti-
convulsant drugs
! Regulates sleep-
wake cycle
GABA
! Major excitatory
neurotransmitter in
CNS
! Regulates
synaptogenesis and
neurogenesis
! Excitotoxity
Glutamate
Synthesized from L-
tryptophan and Vitamin B6
Synthesis of
Serotonin
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Synthesized from L-Tyrosine
Synthesis of Dopamine
and Norepinephrine
24
A biomarker linked to heart disease, stroke, and cognitive
decline
Homocysteine
! Elevated homocysteine levels are a risk factor for
brain atrophy, cognitive impairment, and dementia.
! B-vitamins serve as co-factors for enzymes that
convert homocysteine into methionine
! B-vitamin therapy may slow progression of MCI to
AD by reducing homocysteine levels
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Accelerated rate of atrophy in elderly with MCI can be slowed by
treatment with homocysteine-lowering B vitamins
B-Vitamins Lower Homocysteine
! Randomized, double-blind trial of high dose folic acid,
vitamins B6 and B12 in 271 individuals with MCI
! Treatment group received folic acid (0.8 mg/d), vitamin
B12 (0.5 mg/d), and vitamin B6 (20 mg/day) for 24
months
! Outcome measure: rate of whole brain atrophy assessed
by MRI scans
! Results: Mean rate of brain atrophy was 0.76% in
treatment group and 1.08% in placebo group
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Smith, A. D., Smith, S. M., de Jager, C. A., Whitbread, P., Johnston, C., Agacinski, G., ... & Refsum, H. (2010).
Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a
randomized controlled trial. PloS one, 5(9), e12244.
Homocysteine levels are correlated with rate of brain atrophy
B-Vitamin Therapy Reduces Brain Atrophy
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Supplementing
with B-vitamins
led to 50%
reduction in rates
of brain atrophy in
subjects with MCI
Cerefolin NAC
! Medical food product for the
dietary management of MCI or
early AD
! 5.6 grams L-methlyfolate

800 mcg folic acid

! 2 mg methylcobalamin
! 600 mg N-acetylcysteine
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Bacopa
! Brahmi, an ayurvedic herb
used to promote learning
and memory
! Promotes release of
acetylcholine in prefrontal
cortex and increases anti-
oxidant enzymes
! 300-450 mg/day of extract
containing 55% bacosides
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Ginko Biloba
! Believed to promote learning
and memory
! In some studies GB improves
attention in healthy adults
! 2012 meta-analysis found NO
improvements in attention,
memory or problem solving in
healthy and memory-impaired
populations
30
Huperzine-A
! Alkaloid from r moss
Huperzia serrata
! In some studies, huperzine
is as effective as
prescription medications
used to treat Alzheimers
! Enhances memory in
healthy young adults
! Dose range: 50-200 mcg/
day
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Supplement Stack for Memory/Learning
! Huperzine-A: 50 mcg
! Vitamin B12: 500 mg/day
! Folic Acid: 800 mcg/day
! N-acetylcysteine: 600 mg/day
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To love a person is to learn the song that is in their
heart and to sing it to them when they have forgotten

~Thomas Chandler
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Chronic inammation is associated with cancer, diabetes, heart
disease, obesity, depression and dementia
Chronic Inammation Accelerates Aging
35
Adipocytes secrete a range of pro-inammatory hormones
Is Obesity is a Disease of Inammation?
36
BMI is inversely correlated with total brain volume in healthy middle-
aged adults
As Adiposity Increases, Brain Volume Decreases
37
Interleukin-6
C-Reactive Protein
Leptin
Debette, S., Beiser, A., Hoffmann, U., DeCarli, C., O'Donnell, C. J., Massaro, J. M., ... & Seshadri, S. (2010). Visceral fat is
associated with lower brain volume in healthy middle"aged adults. Annals of neurology, 68(2), 136-144.
Essential fatty acids
Omega-3 Fatty Acids
! Essential fatty acids required for normal metabolism
! EPA, DHA, and ALA
! Sources: Wild sh, seaweed, algae
! Ideal ratio of omega-6:omega-3 is 1:1, but in Western
diets ratio is closer to 16:1
! For general brain health: 2-4 grams of pharmaceutical
grade sh oil/day
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Correlations between prevalence of major depression and sh
consumption
Omega-3 Consumption and Depression
39
Hibbeln, J. R. (1998). Fish consumption and major depression. Lancet, 351(9110), 1213.
Omega-3s reduce inammation, improve triglyceride levels, and
stabilize blood glucose
Omega-3 Fatty Acids and Inammation
40
Omega-3s
EPA/DHA
PPAR-! PPAR-"
!Triglyceride and VLDL secretion " Fatty Acid Oxidation
Improved Blood Lipid Prole
Improved Insulin Sensitivity
" Triglyceride Clearance Improved Glucose Control
! Risk of CVD
Arachidonic Acid
Pro-inammatory
Prostaglandins
COX-2
Potent anti-inammatory compounds derived from plant sources
Polyphenols
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Intake of chocolate, red wine and green tea is associated with better
cognitive function in healthy adults
Flavonoids Improve Cognitive Function
42
Chocolate
10 g/day
Red Wine
.75 glass/day
Green Tea
4 cups/day
Curcumin
! Anti-inammatory via inhibition of cytokine
production
! Anti-cancer effects via induction of apoptosis
! Anti-depressant effects via MAO inhibition
! Inhibits formation of !-amyloid
! For inammatory disorders, 2-8 grams curcumin/day
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Derived from turmeric, a member of the ginger family,
curcurmin has medicinal properties.
An overview of the neuroprotective effects of curcumin
Curcumin Inhibits !-amyloid Formation
44
Lee, W. H., Loo, C. Y., Bebawy, M., Luk, F., Mason, R. S., & Rohanizadeh, R. (2013). Curcumin and its Derivatives: Their
Application in Neuropharmacology and Neuroscience in the 21st Century. Current neuropharmacology, 11(4), 338.
Anti-Inammatory Stack
! 800 mg curcumin twice daily
! 2 mg pharmaceutical grade sh oil
twice daily
! 2 pinches of black pepper mixed in
1 tablespoon of Greek yogurt (to
enhance absorption of curcumin)
! 200 mg CoEnzyme Q10 twice daily
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An anti-inammatory diet that promotes brain health
The Mediterranean Diet
46
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Higher adherence to the MeDi is associated with a trend for reduced risk of
developing MCI and with reduced risk of MCI conversion to AD
Mediterranean Diet and MCI
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Scarmeas, N., Stern, Y., Mayeux, R., Manly, J. J., Schupf, N., & Luchsinger, J. A. (2009). Mediterranean diet and mild cognitive impairment.
Archives of neurology, 66(2), 216
48
Eat food. Not too much. Mostly plants.

~Michael Pollan
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and Exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Organelles within cells that extract energy from nutrients to
synthesize ATP, the cells common energy currency
Mitochondria
50
Cellular power plants that convert nutrients to ATP
Structure of the Mitochondrion
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ROS
Reactive oxygen species are by-products of the electron
transport chain
Formation of ROS in Mitochondria
52
Electron Transport Chain
ATP Synthase
ROS
A classs of anti-oxidants that neutralize ROS
Polyphenols
53
Reduces inammatory, metabolic, and oxidative stress
Health Benets of Resveratrol
! Reduces chronic inammation via inhibition of COX and
NF-"#
! Reduces oxidative stress via de novo synthesis of anti-
oxidant enzymes, SOD and catalase
! Reduces metabolic stress by increasing mitochondrial
biogenesis and fat oxidation
! Resveratrol may prolong life in some animal models but
so far no evidence of life extension in humans
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Resveratrol content in a serving of wine ranges from 0.2 to 2.0 mg/L
Supplements contain anywhere from 100-500 mg
Resveratrol Content in Selected Wines
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Pinot NoirCalifornia

BeaujoulaisFrance

Cabernet and MerlotChile

ZinfandelCalifornia

Cabernet SavignonCalifornia


5.01 mg/L

3.55 mg/L

1.56 mg/L

1.38 mg/L

0.99 mg/L


Derived from the seeds of the tree theobroma cacao, drink of
the gods, cocoa is rich in anti-oxidants
Cocoa
! Improves cardiovascular health by reducing blood
pressure, inhibiting platelet aggregation, and reducing
insulin resistance
! Contains range of bioactive compounds, including
theobromine (similar to caffeine) and phenylethylamine
(a psychostimulant)
! Dark, unsweetened 70% cacao
! Optimal dose 10 g/day
56
Per Capita Chocolate consumption correlates with number
of Nobel Laureates per country
Chocolate Consumption and Nobel Laureates
57
Messerli, F. H., "Chocolate consumption, cognitive function, and Nobel laureates" N Engl J Med 367 (16), 1562 (2012).

Rich in polyphenols, blueberries are potent anti-oxidants
Blueberries
! Blueberries contain anthocyanins, a class of
polyphenols that neutralize free radicals (ROS)
! Inhibit AChE, the enzyme that degrades acetylcholine
! Blueberries stimulate neurogenesis and enhance
neuronal plasticity in the hippocampus
! Improve insulin sensitivity in obese subjects
58
Blueberry Smart
Frappe
! 1 cup ice
! 1/2 cup blueberries
! 1/2 cup blueberry juice
! 2 tablespoons psyllium
husk
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Ubiquinone, an electron carrier in the electron transport chain,
is depleted with normal aging
Coenzyme Q10
! Lack of CoQ10 depletes
cellular energy stores
! May reduce formation of
!-amyloid
! Statin drugs may deplete
levels of CoQ10
! Doses range from
100-300 mg daily
60
Carnitine shuttles fatty acids into mitochondria
Acetyl-L-Carnitine
! Protects endothelium from oxidative damage
! Enhances blood ow
! May slow progression of MCI and Alzheimers
! Dose: 1.5 to 3.0 grams/day
61
A mitochondrial fatty acid used as cofactor in synthesis of ATP
and a potent anti-oxidant
Alpha Lipoic Acid
! Improves symptoms of diabetic neuropathy
! Improves insulin sensitivity
! Acts synergistically with acetyl-L-carnitine as
antioxidant
! May slow progression of Alzheimers
! Dietary sources: Spinach, broccoli
! Supplemental doses: 300-900 mg/day
62
The combination of alpha-lipoid acid and acetyl-l-carnitine
helps restore mitochondrial function
Supplement Stack for Energy
! Acetyl-l-carnitine: 500 mg twice daily
! Alpha-lipoic acid: 300 mg twice daily
! Green tea extract: 200-400 mg twice
daily
! Co-Enzyme Q10: 150 mg twice daily
! B-complex twice daily
63
ALCAR transports fatty acids into matrix
ALA used as cofactor in synthesis of ATP
ECGC reduces ROS
Co Q10 assists in ETC
Vitamin B Complex (folate, B12) reduce homocysteine and
assist in metabolism of proteins, fats, and carbohydrates
~W. Goethe
A meal without wine is
like a day without
sunshine
64
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and Exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Dynamic balance between energy intake and energy expenditure
Energy Intake v. Energy Expenditure
66
Intake
Output
Glycolysis, the Krebs Cycle and the Electron Transport Chain
An Overview of Metabolism
67
AMP:ATP
Glycolysis
Krebs
Cycle
!-oxidation
Electron Transport Chain
AMP protein kinase is activated when ratio of AMP:ATP
increases, an indication that energy is low
AMPK is a Nutrient and Energy Sensor
68
AMPK
Hypothalamus
Food Intake
Skeletal Muscle
FA Oxidation
Glucose Uptake
Expression of Glut4
Mitochondria
Adipose Tissue
Fatty Acid Synthesis
Lipolysis
Pancreas
Insulin Secretion
Liver
Fatty Acid Synthesis
Gluconeogenesis
Cholesterol Synthesis
Heart
Glucose Uptake
Glycolysis
Fatty Acid Oxidation
Even in the absence of manifest type 2 diabetes mellitus or impaired glucose
tolerance, chronically higher blood glucose levels exert a negative inuence on
cognition
Higher Glucose Levels Associated with Lower
Memory and Reduced Hippocampal Volume
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Kerti, L., Witte, A. V., Winkler, A., Grittner, U., Rujescu, D., & Flel, A. (2013). Higher glucose levels associated with lower
memory and reduced hippocampal microstructure. Neurology, 81(20), 1746-1752.
A plant alkaloid used in TCM to treat diabetes
Berberine
! Stabilizes blood glucose, and reduces triglyceride and
LDL-cholesterol levels
! Mechanism of action: activates AMPK, thereby
stimulating glycolysis and !-oxidation
! As effective as metformin in the treatment of type 2
diabetes; potential as a lipid-lowering agent
! Dosage: 300-400 mg 3-4x/day
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A Systemic Review and Meta-Analysis
Berberine in the Treatment of Type 2 DM
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Dong, H., Wang, N., Zhao, L., & Lu, F. (2012). Berberine in the treatment of type 2 diabetes mellitus: a systemic review and
meta-analysis. Evidence-Based Complementary and Alternative Medicine, 2012
Fasting Plasma Glucose
Postprandial Glucose
Hemoglobin A1c
A methylxanthine, coffee is rich in anti-oxidant and
neuroprotective compounds
Coffee
! Enhances cognitive function and reduces
formation of !-amyloid
! Decaffeinated coffee does NOT provide same
level of neuroprotection as caffeinated coffee
! Drinking 3 cups coffee/day associated with 4-
fold slower rate of cognitive decline in study of
elderly men over a 10-year period
! Black coffee or espresso are best choices
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High plasma caffeine levels over a 2-4 year observation period were
associated with lack of progression of MCI to dementia
High Blood Caffeine Levels in MCI Linked
to Lack of Progression to Dementia
73
Cao, C., Loewenstein, D. A., Lin, X., Zhang, C., Wang, L., Duara, R., ... & Arendash, G. W. (2012). High blood caffeine levels in
MCI linked to lack of progression to dementia. Journal of Alzheimer's Disease, 30(3), 559-572.
Cinnamoman Cassia (Ceylon Cinnamon) stabilizes blood sugar and
reduces lipids
Cinnamon
! Meta-analyses demonstrate that cinnamon lowers fasting
plasma glucose, triglycerides, and LDL cholesterol in
patients with type 2 diabetes
! Anti-inammatory and anti-cancer effects have been
demonstrated in vitro
! Reduces formation of !-amyloid in animal models of
Alzheimers disease
! Supplemental doses: 1-6 grams/day
! Contains coumarin, which may cause drug-drug
interactions
74
In a meta-analysis of 10 RCTs (n = 543 patients), cinnamon doses of
120 mg/d to 6 g/d for 4 to 18 weeks reduced fasting blood glucose
Cinnamon Use in Type 2 Diabetes
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Allen, R. W., Schwartzman, E., Baker, W. L., Coleman, C. I., & Phung, O. J. (2013). Cinnamon use in type 2 diabetes: an updated systematic
review and meta-analysis. The Annals of Family Medicine, 11(5), 452-459.
Saturated fatty acids containing 6-12 carbon atoms
Medium-Chain Triglycerides
! Coconut oil is composed of ~65% MCTs
! MCTs are metabolized to ketone bodies, which
improve cognition in patients with mild memory
impairment
! Axona, a medical food product containing MCTs,
improves cognitive function in patients with MCI
or AD
! Dose of MCTs: 5-40 grams/day
76
Improvements in cognition correlate with levels of the ketone
body !-hydroxybutyrate
Ketosis in Alzheimers Disease
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Henderson, S. T. (2008). Ketone bodies as a therapeutic for Alzheimer's disease. Neurotherapeutics, 5(3), 470-480.
Smart Coffee
! 1 cup of caffeinated
black coffee
! 1/2 tablespoon
coconut oil
! 1/4 teaspoon of
cinnamon
78
Immune Stress and Anti-Inammatory Nutrients
Adiposity, brain volume, and chronic inammation
Oxidative Stress and Anti-Oxidants
Mitochondria, reactive oxygen species and polyphenols
Metabolic Stress and Nutrients that Support Metabolism
Nutrient sensors, elevated blood sugar, and type 3 diabetes
Strategies to Protect The Aging Brain
Caloric Restriction and exercise
How The Brain Ages
The insidious effects of chronic physical and psychological stress
1
2
3
4
5
Decrease of 30% to 60% of ad libitum feeding without
malnutrition
Caloric Restriction
! Increases lifespan across a range of animal
species
! CR improves memory, cognitive function and
overall health in humans
! Little or no evidence that CR extends life in
humans
80
20% increase in verbal memory after only 3 months of CR
Caloric Restriction Improves Memory
81
Witte, A. V., Fobker, M., Gellner, R., Knecht, S., & Flel, A. (2009). Caloric restriction improves memory in
elderly humans. Proceedings of the National Academy of Sciences, 106(4), 1255-1260.
n=50
An alternative to daily CR
Intermittent Fasting
! Nutrient strategy that alternatives brief periods (<24
hours) of fasting with non-fasting
! Improves blood glucose, lipid proles and cognitive
function
! CF and IF reduce inammation, increase BDNF, improve
insulin signaling, and inhibit mTOR
! These physiologic changes are similar to those seen with
aerobic exercise
82
Easter Island, located in Southeaster Pacic Ocean
Rapa Nui
83
Highly-conserved
metabolic switches
mTOR and AMPK
! mTOR: anabolism
! AMPK: catabolism
84
Glycolysis
Krebs
85
Carbohydrate metabolism
Lipid metabolism
Protein
metabolism
Cell Growth and
Apoptosis
Aging
AMPK
mTOR
Aerobic Exercise and Nutraceuticals
Mimic The Cellular Effects of CR/IF
86
Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R. (2012). Of mice and men: the benets of
caloric restriction, exercise, and mimetics. Ageing research reviews, 11(3), 390-398
Resistance training protects against sarcopenia and endurance
training increases mitochondrial biogenesis
Benets of Resistance and Endurance Training
87
Regular physical activity builds a better brain
Benets of Aerobic Exercise
! Increases Brain-Derived Neurotrophic Factor
! Increases neurogenesis and synaptogenesis
! Increases brain volume in older adults
! Improves cognitive function
! Inoculates the brain against depression
! 75% MHR for 30 minutes, 5x/week
88
Aerobic Exercise Training Increases
Brain Volume In Aging Adults
Blue regions: Gray matter volume was increased for aerobic exercisers
Yellow regions: White matter was increased for aerobic exercisers
Colcombe SJ, Erickson KI, Scalf PE, et al. Aerobic exercise training increases brain volume in aging humans. The
Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2006;61(11):11661170.
Resistance training improves physical and cognitive function
Benets of Resistance Training
! RT improves short-term memory in older adults
! RT improves insulin sensitivity and protects against the
development of type 2 DM
! RT is the ONLY intervention that protects against age-
related muscle loss
! 75-85% 1 RM weight, 10-15 total reps, once/week
90
Leisurely Walks in Nature
Intermittent
Fasting
Omega-3 Fatty
Acids
Interval
Training
Nutrition and Exercise Strategy for Protecting The
Aging Brain
91
Resistance
Training
Leisurely outdoor activities 5 days/
week
4 grams of EPA+DHA daily
Fast for 12-18 hours 3x/week
2 sessions/week; 20 seconds work; 20 minutes total
Resistance Training, once/week
~Ayurvedic Proverb
When diet is wrong, medicine is of no use;
When diet is correct, medicine is of no need
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