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Prof.dr.

Hardi Darmawan, MPH&TM, FRSTM, AIF


Sriwijaya Medical School
Palembang, South Sumatra - Indonesia
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Greta Garbo

Indonesian Life Expectancy


2000 2005
2020 2025

: 67.8 years
: 73.6 years

Saparman,Sragen (143 yrs)

Mak Encuh, Bandung (131 yrs)


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Aging is not an inevitable


process leading to disease and
deterioration
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NORMAL AGING

Despite stereotype most of the elderly age well !


Most of our images are based on the frail sub-

set who frequently use medical services


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Normal Aging
Generally normal
aging in
associated with a
reduction in
functional reserve
capacity in tissues
and organs.
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Normal Aging
At advanced age more
common to see
evidence of impaired
homeostasis and
response to external
insults e.g. illness.

Temperature Regulation and Aging


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Risk Factors for Hypothermia


in Elderly
Decreased thermogenesis
Decreased vasoconstriction in response to cold
Decrease in intensity of shivering
Medications e.g. Chlorpromazine
Socio-economic (nutrition, heating, etc)
Co-morbidities including falls / immobility

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Risk Factors
for Hypothermia in Elderly
Decreased ability to

sweat
Decreased ability to
redirect heat :
Reduced capacity for

vasodilation peripherally
Modest ability to
increase cardiac output
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Summary of Normal Aging Changes


Despite stereotype most of the elderly age well!
Most of our images are based on the frail sub-set
who frequently use medical services
Generally normal aging in associated with a
reduction in functional reserve capacity in tissues
and organs
At advanced age more common to see evidence of
impaired homeotasis and reponse to external
insults eg. Illness.
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Characteristic of Aging
Mortality increases exponentially
Biochemical composition of tissue changes
Physiologic capacity decreased
Ability to maintain homeostasis diminishes
Susceptibility and vulnerability to disease
increases

Environmental and Genetic factors influence


the rate of age
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Characteristic of Aging
Loss of physiologic reserve and decreased

homeotatic control may result from :


Allostatic load (persistent activation of normal

neuroendrocrine, immune and autonomic


responses to stress)
Development of homeostasis (altered
response to physiologic stresses)

Changes are generally irreversible


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Theories of Aging : Oxidative Stress


Synopsis : Oxygen converted during
metabolism causes protein, lipid and DNA
damage over time
In support :
Mutations in oxidative stress pathway can

extend life span


Mutations in other pathways that increase
longevity resist oxidative damage
In opposition : antioxidants do not delay
human senescence or disease
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Systemic Inflammatory = Silent,


Minimally Persistent Inflammation

AA, arachidonic Acid (Omega 6) high in

contemporary diet
Higher AA in cell membranes
AA reacts avidly than EPA with cyclo-

oxygenase enzyme
AA-eicosanoids > EPA-eicosanoids systemic
inflammation
Silent inflammation = inflammation without
the 5 cardinal signs
Pain, red, swell, heat and loss of function
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Glycation Theory
Occurs in everyone, but a faster rate in

diabetics
Reaction with glucose with macromolecules
Devastating effects on macromolecules
Condition related to AGE
Senile dementia
Vascular Stiffening
Cataract
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Oxidative Stress Bodily Damage


Heart disease

Hypertension
Cancer
Inflammatory bowel disease (IBD)
Arthritis
Diabetes

Alzheimers disease
Stroke
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Free Radical Theory


Oxidative Stress = Free Radicals > Antioxidants
Effect
Free Radical overactivity
Imbalance between

antioxidant Free radicals


Oxidative stress

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Free Radical Theory


Oxidative Stress = Free Radicals >
Antioxidants
Accelerated Aging
Diabetes
Sun exposure
Poor Nutrition
Stress

revisi ke-2

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Physiology of Aging
Why do we need to know the

physiology of aging?
to tell the difference between
physiological and pathological
phenomena in the geriatric population
To appreciate the impact of normal
age-related degeneration on diseases
and their management.
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Goals of
Successful Aging
Compression of
debilitating disease into

final portion of life


Maintain high-level of
function until end of life
Death with dignity and
comfort
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Health Model
Anti aging internal health
Aesthetic external health
Regenerative - rejuvenation

revisi ke-2

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Why do we age?
2 categories of theories :
Aging events occur randomly and accumulate
in time : Stochastic Theory
Accumulated errors in making bodily and cell
proteins Error Catastrophe Theory
Cross-linking of big molecules such as
proteins accumulates over time Crosslinking theory
Repeated damage to DNA and incomplete
repair wear and Tear Theory
Aging is inevitable : Nonstochastic Theory
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Why do we age?
2 categories of theories :
Aging is inevitable : Nonstochastic Theory
Certain organ-systems such as hypothalamus,
immune and neuroendocrine systems have
in-built pacemakers that involute with age
pacemaker theory
There is familiar predisposition for longevity
and thus there may be a genetic basis for
aging genetic theory
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Sarcopenia
Between ages 30 and 75:
Lean body mass decreases
due to loss of skeletal muscle
mass
Number and size of muscle
fibers progressively decrease.

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Endocrine Changes with Aging

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Hormone Deficiencies many if not most of the signs,


complaints, causes of Senescence
Age-related signs :
- wrinkles
- skin & hair thinning
- hair loss
- muscle atrophy
- abdominal obesity

Age-related
diseases :
- cardiovascular
- cancer
- obesity
- diabetes
- osteoporosis
- dementia

Age-related
physiology :
- Intestinal transit
- cardiac output
- kidney function
- liver function

Age-related symptoms :
- fatique
- cognition
- depression

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5 Strategies of Healthy Aging

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Balanced Diet
Energy intake

50/25/25
50% Carbohydrate
fruits & vegetables
25% Protein 2/3
plant, 1/3 meat
preferably fish
25% Fat (mono &
poly) unsaturated

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Balanced Anti Aging Diet


Caloric restriction

Keep low end of ideal


body weight
Okinawan diet

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Okinawan Diet
7 servings of vegetables

7 servings of grains
4 servings of fruits
Abundance of soy
3 times per week fish
Alcohol in moderation

Low caloric diet

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Positive Food Intake


Fruits Minerals & Vitamin
Vegetables Fibres &

Phytonutrients
Spices Hormone modulator,
Cancer Preventive
Mushrooms/Ginsengs Adaptogen
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Killer Intake - Delicious


Avoid high fat, salt,

sugar
Avoid trans fatty acid
cooked fat
Avoid acralamide
heated carbohydrate
Avoid preservatives &
additives
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Colour Agents

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Dietary Risk Factors


American Cancer Society Study
150000
20 year study
53% higher risk of distal colon cancer in red

meat eater

John Hopkins Bloomberg Study


Higher sugar intake increase cancer risk
Eat nut & Beans
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Hydration
Drink liquids (ml) = 33 x body weight

(kg)/day
Hydrate before during & after exercise
Test hydration status
Specific gravity - 1020

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Precision of Anti Aging Exercise


Exercise to be stronger, younger & healthier

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Aim of Anti Aging Exercise


Balance Coordination
Strength: Muscular
Cardiovascular
Stretch: flexibility, posture
& range of motion
Better circulatory system
Lymphatic massage
Mental alertness
Degenerative Disease
Prevention
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Balance

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Musculoskeletal Composition
Deterioration in Aging

&

30 year old

75 year old

30% - muscle

15% - muscle

20% - adipose tissue

40% - adipose tissue

10% - bone

8% - bone

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Types of Exercise
Five main types of exercise
Strength build muscle, HGH
stimulation
Aerobics cardiopulmonary
conditioning
Intervals accommodate heart
size to demand
Stretching flexibility
Eastern balance &
coordination
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Osteoporosis and Fractures


Low dietary intake of

calcium
Loss of endocrine
protection
Reduced endogenous
production of vitamin D
Disuse
Disease Chronic Renal
Disease, Rheumatoid
Arthritis, Thyroid Disease
Medications Steroids,
Thyroxin.
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Osteoporosis

Age related disorder,


aging disease major morbidity/mortality
atherosclerosis CV diseases
metabolic syndrome
tumors
neurodegenerative
diseases
ld

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Osteoporosis
till

Asymptomatic bone fracture & complication


bone mineral density

risk

Loss of architectural integrity

Fragility fracture

Should understand

physiology

pathophysiology
Immuno senescence & inflammatory of aging
Immuno senescence lifelong antigenic load
chronic immune system activation
hyper
proinflammatory
production
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Proinflammatory cytokines - IL-1, IL-6,

TNF inverse CRP


Immuno senescence shape the same
immunological cell & cytokine
TNF, IL-1, Rank-L, M-CSF expression
osteoclast precursor
Why not build the osteoblast
aging & estrogen deficiency : most

important risk - osteoporosis

Immune Mechanism of Osteoporosis


The skeleton is physiologically in a state of

dynamic equilibrin between


formation
osteoblasts

vs
vs

reabsorption
osteoclasts

tuning by cytokins
growth factors

accumulation

Age immune profile


memory/effector cells expressing

Rank L resident in bone


secreting
osteoclastogenic
proinflammatory cytokins

Natural Bone
Building Plan
1. Hormones
2. Minerals
3. Vitamins

4. Diet
5. Digestion

6. Exercise
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Hormones
Vit D is a steroid hormones
Determinant for bone
health & all ages
determinant

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Summary of Hormones to treat bone loss (1)


1. Estrogen to prevent bone loss : estradiol
transdermal titrated area 1 mg/ml
2. Progesterone

To build bone & balance estrogen


50-300mg oral / transdermally
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Summary of Hormones to treat bone loss (2)


3. DHEA/testosterone

Start DHEA (5-25 mg/day)


Testosterone 1-5 mg/night

4. Melatonin (0.5 3 mg/night)


5. GH if IgF -1 low or below mid range
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Summary of Vitamins to treat Bone Loss


1. Vitamin D3

2. Vitamin K2
3. Vitamin C
4. Vitamin B

5. Vitamin E

2000-5000 u/d
50-150 mcg/d
1000mg 4000mg/d
100mg/d, if
homocysteine not
improving use
Methyl B12/ folic
acid
200-800 U
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Summary of Mineral to treat Bone Loss


1.

Magnesium

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Diet & Bone Health


Enzyme function optimally at PH neutral
Acidic by products accelerate bone loss
High protein & diary (western diet) chronic metabolic

acidosis
Bones ability to neutralize acid load -- depend on KT
stores
K+ intertitial fluid
K+ Ca++ from bone to buffer in a place of KT
chronic high steroids
diuretics

KT

Eating alkaline diet


Rich fresh fruit vegetables
Limited protein & diary
Artificial sweetness
Preservatives

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Acidifying Foods
Sugar
Yeast, wheat breads
Soft drinks, alcohol, tea,
coffee
Cranberries
Sweet potato
Salt
HOPS
Corn oil
White balsamic vinegar
Saccharine, aspartame
benzoate

Alkalinizing Foods
Honey, maple syrup, stevia
Goats milk
Soy milk
Umeboshi plums
Sea salt
Most herbal teas
Lemon, limes, grapefruit,
onion
Olive oil
Miso
Most fruits & vegetables
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Unhealthy Ageing

Healthy Ageing

Mrs. B.Gozali,MD 84 years old


She was doing her flying fox (30 meters height from ground).
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is

SIRT1
a
Implicated in

Audrey Hepburn

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SIRT 1
A key mediator of beneficial effects of :

Caloric restriction
Regulates lipid
Regulates glucose
Regulates metabolism
By deacetylating metabolic regulators
SIRT1 levels are regulated by microRNAs
(miRs)

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Telomerase Theory of Aging


Geron Corporation (Menlo Park, California)
Telomeres : sequences of nucleic acids extending from the

ends of chromosoms
Telomeres : maintain integrity of chromosoms
Telomeres shortened cellular damage

Cellular death

aging
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ld

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revisi ke-2

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with unhealthy aging and a


shorter life span
Telomeres from the ends of
human chromosome

Telomeres shortened
limit proliferation of human
cells, by inducing :
Replicative senescence
Differentiation
Apoptosis
Increasing cancer risk
Telomere Shortening & Aging (2007).
H.Jiang, Z.Ju, K.L Rudolph: Z Gerontol. Geriat 40:314-324
revisi ke-2

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Short Telomeres have been associated


with maladies in these tissue :
Immune cells

memory and nave


Heart
cardiomyocytes
Hematopoietic stem
cells
Lung alveolar cells
Skin dermis,
epidermis,
vasculature
Vascular intima
(endothelium)

Osteoblasts, MSCs
Retinal pigmented tissue of

eye
Chondrocytes
Skeletal muscle
Kidney cortex
Neurons

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The Seven Step Program :

1.
2.
3.
4.
5.
6.
7.

Nutritional Modification
Nutrient Supplementation
Herbs
Pharmaceuticals
Hormone Replacement Therapy
Mental Training
Mind / Body Exercise
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ld

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Maria Olivia da Silva


132 tahun
Brasil
Lahir : 28
Feb 1880
2 x menikah
Anak 14

70
ld

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