Physiology of Aging

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Laboratorium Fisiologi
FK UNEJ
 Objectives

 Discuss the Characteristics of Aging

 Review the various Theories of Aging
 Explore the effects of Aging on the different
organ systems
 Penuaan
 DefinisiMenua =>
 Suatu proses menghilangnya secara perlahan
perlahan kemampuan jaringan untuk
memperbaiki diri/mengganti diri dan
mempertahankan struktur dan fungsi
normalnya sehingga tidak dapat bertahan
terhadap jejas dan memperbaiki kerusakan
yang diderita (constantinedes,1994)
CHARACTERISTICS OF AGING

 Mortality increases exponentially

 Biochemical composition of tissue changes
 Physiologic capacity decreases
 Ability to maintain homeostasis diminishes
 Susceptibility and vulnerability to disease
increases

Environmental and Genetic factors

influence the rate of aging
 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
 THEORIES OF AGING:
IMMUNOLOGIC

Synopsis: Time-acquired deficits, primarily in T-

cell function, increase susceptibility to infections
and cancer

In support: Some diseases are associated with

aging

In opposition: Immunologic function is apparently

not directly related to healthy aging
 THEORIES OF AGING:
GENETIC
Synopsis: Senescence results from activation or suppression
of specific “aging” genes

In support:
Longevity appears to be hereditable
Some genetic disorders lead to accelerated aging

In opposition:
Evolutionary pressures appear to select for reproductive
fitness rather than senescence
Little direct evidence of “genetic programming” of
senescence in humans
Aging effects on organ
systems
 Cardiovascular

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 Cardiovascular: Structure
Age-associated change
↑ vascular intimal thickening
↑ vascular stiffness
↑ LV wall thickness
↑ Left Atrial size
Possible disease
outcomes
Early stages of atherosclerosis
Systolic HTN
Stroke
Atherosclerosis
↓ early diastolic cardiac filling
↑ cardiac filling pressure
Lower threshold for dyspnea
Lone Atrial Fibrillation
 Cardiovascular: Function

Age-associated change Possible disease outcomes

Altered regulation of vascular Vascular stiffening

tone Hypertension

Decreased cardiovascular Lower threshold for and

reserve increased severity of heart
failure
 Pulmonary

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 Pulmonary - Structure
 ↓ Alveoli and lung capillaries
 ↓ Number and elasticity of parenchymal elastic fibers
→ Gradual loss of elastic recoil of the lungs
 Airway size ↓
 Ciliary action less effective
 Chest wall stiffens
 Respiratory muscles weaken
 ↓ lung mass
 Diaphragm weakens by 25%
Pulmonary - Function
 Pulmonary – Function
↓ FEV1 and FVC
 ↑ Residual volume

 Ventilation-Perfusion mismatching causes ↓

PaO2 [100 – (0.32 * age)]
 Maximum inspiratory and expiratory
pressures ↓
 Diffusion of CO decreased

 Decreased ventilatory response to hypercapnia

Renal
 Renal - Structure

↓ Renovascular bed → ↓ Renal Blood flow

 Selective loss of cortical vasculature
 Renal mass ↓ 25% - mainly cortical
 Renal weight ↓
 Renal - Function
↓ Cr clearance & GFR (10mL/decade) → ↓
excretion of drugs, toxins
 ↓ concentrating and diluting capacity
 ↓ serum renin and aldosterone (30-50%)
→ fluid and electrolyte abnormalities - ↑ volume
depletion and dehydration
→ ↑ risk of hyerkalemia
→ ↓ Na & K excretion and conservation
↓ vitamin D activation
GI
 GI - Structure
Age-associated change
↓ liver size and blood flow
Possible disease
outcomes
Impaired clearance of drugs
requiring phase I metabolism

Impaired response to gastric Increased risk of gastric &

mucosal injury duodenal ulcers
↓ pancreatic mass and enzyme Increased insulin resistance
reserves
↓ in effective colonic contractions Constipation
↓ in gut-associated lymphoid tissue Increased risk of gastric &
duodenal ulcers
 GI - Function
Age-associated change Possible disease
outcomes
↓ stomach acid production Atrophic gastritis

Impaired acid clearance GERD

Slowing of gastric emptying Prolong gastric distention

↑ meal-induced satiety
↓ Ca absorption Bone loss
Delay in colonic transit Constipation
↓ rectal wall sensitivity
↓ tensile strength in smooth muscle Diverticulosis
of colonic wall
↓ Insulin secretion ↑ Insulin resistance
 Endocrine
 Thyroid gland – moderate atrophy
 Ovarian failure

 ↓ T3

 ↓ DHEA

 ↑ PTH

 ↓ GH, testosterone, estrogen

 ↓ Insulin secretion → Impaired glucose

tolerance
 Hematology

% of marrow space occupied by hematopoietic

tissue declines
 ↓ stem cells in marrow

 Slowed erythropoiesis ↓ incorporation of iron

into RBC
 Average values of Hb and hematocrit ↓
slightly
Central Nervous System – Structure
↓ Brain Weight
 ↓ no. of nerve cells in brain

 ↓ cerebral blood flow (20%)

 ↑ neurofibrillary tangles and scattered senile

plaques
 Altered neurotransmitters
Central Nervous System - Function
Intellect
 Maintained until at least age 80

 Slowing in central processing → Tasks take longer

to perform
Verbal skills
 Maintained until age 70

 Gradually ↓ in vocabulary, ↑ semantic errors and

abnormal prosody
Mentation
 Difficulty learning, especially languages and
forgetfulness in non-critical areas – doesn’t impair
recall of important memories or affect function
 Peripheral Nervous System

↓ spinal motor neurons

 Nerve conduction slows
↓ vibratory sensation – especially feet
↓ thermal sensitivity (warm-cool)
↓ size of large myelinated fibers
 Musculoskeletal - Muscle

↓ muscle fibers → ↓ muscle mass (sarcopenia)

→ lean body mass
 Infiltration of fat into muscle bundles
 ↑ Fatigability
↓ Basal metabolic rate (4%/decade after age
50)
 Musculoskeletal - Bone
 ↓ Bone density – both trabecular and cortical bone
 ↓ Osteoclast bone formation
 ↓ Bone remodelling
 ↑ adipocyte formation in bone marrow
 Slower healing of fractures
 ↓ Vitamin D absorption → ↓ osteoblasts → ↓ bone
formation
 ↑ Bone loss → Loss of height (stooping) and Dorsal
Kyphosis
 ↓ Bone density & microarchitectural bone deterioration
→ Osteoporosis
 Musculoskeletal - Joints
Non-articular cartilage grows throughout life
Articular cartilage does change
 ↓ thickness of cartilage

 ↓ chondrocytes

 Collagen becomes stiffer → Disordered

cartilage matrix
 As a result, less able to handle mechanical
stress
 Skin

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 Skin - Structure
Epidermal changes
Melanocytes
 ↓ 15%/decade
 Density doubles on sun-exposed skin
 ↑ lentigines

Langerhans cells
 ↓ density
 ↓ responsiveness

Dermal Changes
 ↓ collagen – 1% annual decline, altered fibers
 ↓ density
 Progressive loss of elastic tissue in the papillary dermis
 Skin - Function
Physiologic Decrement Clinical Consequence (s)

↓ Barrier function Dryness

Slower Cell replacement Rough surface

Delayed healing

Ineffective DNA repair ↑ photocarcinogenesis

↓ Elasticity Lax skin

↓ Immunologic and Chronic low-grade skin

inflammatory responsiveness infections
Inapparent injuries and infections
 Skin – Function (Cont’d)
Physiologic Decrement Clinical Consequence (s)

Mechanical protection altered Frequent injuries

↓ Sensory perception
↓ Sweating Tendency to hypothermia

↓ effectiveness of Vulnerability to heat and cold

thermoregulation (vascular)
↓ Vitamin D production Osteomalacia

Impaired Wound healing Persistent wounds, weak scars

 Immune system
 ↓ Cell-Mediated immunity
 Lower affinity antibody production
 ↓ delayed-type hypersensitivity
 ↑ Interferon-gamma, TGF-beta, TNF, IL-6, IL-1 production
causing impaired macrophage function
 ↑ circulating IL-6
 ↓ IL-2 release and IL-2 responsiveness
 ↓ production of B cells by bone marrow

Resulting in ↓ immunity contributing to ↓ susceptibility to

infections and malignancy
 Sensory - Vision

 Yellowing of lens
 Impaired dark adaptation
 Inability to focus on near items (Presbyopia)
↓ Contrast sensitivity
↓ Lacrimation → Dry eyes
 Sensory – Smell and Thirst

Smell
 Detection ↓ by 50%

Thirst
↓ thirst drive
 Impaired control of thirst by endorphins
 Sensory - Audition
 Bilateralloss of high frequency tones
 Thickened eardrum

 Central processing deficit

 Difficulty discriminating source of sound

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 Impaired discrimination of target from
noise