Physiology of AgingPhysiology of Aging

Laboratorium Fisiologi

FK UNEJ

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ObjectivesObjectives

Discuss the Characteristics of AgingDiscuss the Characteristics of Aging

Review the various Theories of AgingReview the various Theories of Aging

Explore the effects of Aging on the different Explore the effects of Aging on the different

organ systemsorgan systems

PenuaanPenuaan

Definisi Menua => Definisi Menua => Suatu proses menghilangnya secara perlahan Suatu proses menghilangnya secara perlahan

perlahan kemampuan jaringan untuk perlahan kemampuan jaringan untuk memperbaiki diri/mengganti diri dan memperbaiki diri/mengganti diri dan mempertahankan struktur dan fungsi mempertahankan struktur dan fungsi normalnya sehingga tidak dapat bertahan normalnya sehingga tidak dapat bertahan terhadap jejas dan memperbaiki kerusakan terhadap jejas dan memperbaiki kerusakan yang diderita (constantinedes,1994)yang diderita (constantinedes,1994)

CHARACTERISTICS OF AGINGCHARACTERISTICS OF AGING

Mortality increases exponentiallyMortality increases exponentially Biochemical composition of tissue changesBiochemical composition of tissue changes Physiologic capacity decreasesPhysiologic capacity decreases Ability to maintain homeostasis diminishesAbility to maintain homeostasis diminishes Susceptibility and vulnerability to disease Susceptibility and vulnerability to disease

increasesincreases

Environmental and Genetic factorsEnvironmental and Genetic factorsinfluence the rate of aginginfluence the rate of aging

THEORIES OF AGING: THEORIES OF AGING: OXIDATIVE STRESSOXIDATIVE STRESS

Synopsis:Synopsis: Oxygen converted during metabolism Oxygen converted during metabolism causes protein, lipid, and DNA damage over timecauses protein, lipid, and DNA damage over time

In support:In support: Mutations in oxidative stress pathway can extend life Mutations in oxidative stress pathway can extend life

spanspan Mutations in other pathways that increase longevity Mutations in other pathways that increase longevity

resist oxidative damageresist oxidative damage

In opposition:In opposition: Antioxidants do not delay human Antioxidants do not delay human senescence or diseasesenescence or disease

THEORIES OF AGING: THEORIES OF AGING: IMMUNOLOGICIMMUNOLOGIC

Synopsis:Synopsis: Time-acquired deficits, primarily in T-Time-acquired deficits, primarily in T-cell function, increase susceptibility to infections cell function, increase susceptibility to infections and cancerand cancer

In support:In support: Some diseases are associated with Some diseases are associated with agingaging

In opposition:In opposition: Immunologic function is apparently Immunologic function is apparently not directly related to healthy agingnot directly related to healthy aging

THEORIES OF AGING: THEORIES OF AGING: GENETICGENETIC

Synopsis:Synopsis: Senescence results from activation or suppression Senescence results from activation or suppression of specific of specific ““agingaging”” genes genes

In support:In support: Longevity appears to be hereditableLongevity appears to be hereditableSome genetic disorders lead to accelerated agingSome genetic disorders lead to accelerated aging

In opposition: In opposition: Evolutionary pressures appear to select for reproductive Evolutionary pressures appear to select for reproductive

fitness rather than senescencefitness rather than senescenceLittle direct evidence of Little direct evidence of ““genetic programminggenetic programming”” of of

senescence in humanssenescence in humans

Aging effects on organ Aging effects on organ systemssystems

CardiovascularCardiovascular

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Cardiovascular: StructureCardiovascular: Structure

Age-associated changeAge-associated change Possible disease Possible disease outcomesoutcomes

↑ ↑ vascular intimal thickeningvascular intimal thickening Early stages of atherosclerosisEarly stages of atherosclerosis

↑ ↑ vascular stiffnessvascular stiffness Systolic HTNSystolic HTN

StrokeStroke

AtherosclerosisAtherosclerosis

↑ ↑ LV wall thicknessLV wall thickness ↓↓ early diastolic cardiac fillingearly diastolic cardiac filling

↑ ↑ cardiac filling pressurecardiac filling pressure

Lower threshold for dyspneaLower threshold for dyspnea

↑ ↑ Left Atrial sizeLeft Atrial size Lone Atrial FibrillationLone Atrial Fibrillation

Cardiovascular: FunctionCardiovascular: Function

Age-associated changeAge-associated change Possible disease outcomesPossible disease outcomes

Altered regulation of vascular Altered regulation of vascular tonetone

Vascular stiffeningVascular stiffening

HypertensionHypertension

Decreased cardiovascular Decreased cardiovascular reservereserve

Lower threshold for and Lower threshold for and increased severity of heart increased severity of heart failurefailure

PulmonaryPulmonary

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Pulmonary - StructurePulmonary - Structure

↓ ↓ Alveoli and lung capillariesAlveoli and lung capillaries ↓ ↓ Number and elasticity of parenchymal elastic fibers Number and elasticity of parenchymal elastic fibers

→ Gradual loss of elastic recoil of the lungs→ Gradual loss of elastic recoil of the lungs Airway size ↓Airway size ↓ Ciliary action less effectiveCiliary action less effective Chest wall stiffensChest wall stiffens Respiratory muscles weakenRespiratory muscles weaken ↓ ↓ lung masslung mass Diaphragm weakens by 25%Diaphragm weakens by 25%

Pulmonary - FunctionPulmonary - Function

Pulmonary – FunctionPulmonary – Function

↓ ↓ FEVFEV11 and FVC and FVC ↑ ↑ Residual volumeResidual volume Ventilation-Perfusion mismatching causes ↓ Ventilation-Perfusion mismatching causes ↓

PaOPaO2 2 [100 – (0.32 * age)][100 – (0.32 * age)]

Maximum inspiratory and expiratory Maximum inspiratory and expiratory pressures ↓pressures ↓

Diffusion of CO decreasedDiffusion of CO decreased Decreased ventilatory response to hypercapniaDecreased ventilatory response to hypercapnia

RenalRenal

Renal - StructureRenal - Structure

↓ ↓ Renovascular bed → ↓ Renal Blood flowRenovascular bed → ↓ Renal Blood flow

Selective loss of cortical vasculatureSelective loss of cortical vasculature

Renal mass ↓ 25% - mainly corticalRenal mass ↓ 25% - mainly cortical

Renal weight ↓Renal weight ↓

Renal - FunctionRenal - Function

↓ ↓ Cr clearance & GFR (10mL/decade) → ↓ Cr clearance & GFR (10mL/decade) → ↓ excretion of drugs, toxinsexcretion of drugs, toxins

↓ ↓ concentrating and diluting capacityconcentrating and diluting capacity ↓ ↓ serum renin and aldosterone (30-50%) serum renin and aldosterone (30-50%)

→ → fluid and electrolyte abnormalities - ↑ volume fluid and electrolyte abnormalities - ↑ volume depletion and dehydrationdepletion and dehydration

→ ↑ → ↑ risk of hyerkalemiarisk of hyerkalemia

→ ↓ → ↓ Na & K excretion and conservationNa & K excretion and conservation ↓ ↓ vitamin D activationvitamin D activation

GIGI

GI - StructureGI - StructureAge-associated changeAge-associated change Possible disease Possible disease

outcomesoutcomes↓ ↓ liver size and blood flowliver size and blood flow Impaired clearance of drugs Impaired clearance of drugs

requiring phase I metabolismrequiring phase I metabolism

Impaired response to gastric Impaired response to gastric mucosal injurymucosal injury

Increased risk of gastric & Increased risk of gastric & duodenal ulcersduodenal ulcers

↓↓ pancreatic mass and enzyme pancreatic mass and enzyme reservesreserves

Increased insulin resistanceIncreased insulin resistance

↓↓ in effective colonic contractionsin effective colonic contractions ConstipationConstipation

↓↓ in gut-associated lymphoid tissuein gut-associated lymphoid tissue Increased risk of gastric & Increased risk of gastric & duodenal ulcersduodenal ulcers

GI - FunctionGI - FunctionAge-associated changeAge-associated change Possible disease Possible disease

outcomesoutcomes↓↓ stomach acid productionstomach acid production Atrophic gastritisAtrophic gastritis

Impaired acid clearanceImpaired acid clearance GERDGERD

Slowing of gastric emptyingSlowing of gastric emptying Prolong gastric distention Prolong gastric distention ↑ ↑ meal-induced satietymeal-induced satiety

↓ ↓ Ca absorptionCa absorption Bone lossBone loss

Delay in colonic transit Delay in colonic transit ↓ ↓ rectal wall sensitivityrectal wall sensitivity

ConstipationConstipation

↓ ↓ tensile strength in smooth tensile strength in smooth muscle of colonic wallmuscle of colonic wall

DiverticulosisDiverticulosis

↓ ↓ Insulin secretionInsulin secretion ↑ ↑ Insulin resistanceInsulin resistance

EndocrineEndocrine

Thyroid gland – moderate atrophyThyroid gland – moderate atrophy Ovarian failureOvarian failure ↓ ↓ T3 T3 ↓ ↓ DHEADHEA ↑ ↑ PTHPTH ↓ ↓ GH, testosterone, estrogenGH, testosterone, estrogen ↓ ↓ Insulin secretion → Impaired glucose Insulin secretion → Impaired glucose

tolerancetolerance

HematologyHematology

% of marrow space occupied by hematopoietic % of marrow space occupied by hematopoietic tissue declinestissue declines

↓ ↓ stem cells in marrowstem cells in marrow Slowed erythropoiesis ↓ incorporation of iron Slowed erythropoiesis ↓ incorporation of iron

into RBCinto RBC Average values of Hb and hematocrit ↓ Average values of Hb and hematocrit ↓

slightlyslightly

Central Nervous System – StructureCentral Nervous System – Structure

↓ ↓ Brain WeightBrain Weight ↓ ↓ no. of nerve cells in brainno. of nerve cells in brain ↓ ↓ cerebral blood flow (20%)cerebral blood flow (20%) ↑ ↑ neurofibrillary tangles and scattered senile neurofibrillary tangles and scattered senile

plaquesplaques Altered neurotransmittersAltered neurotransmitters

Central Nervous System - FunctionCentral Nervous System - FunctionIntellectIntellect Maintained until at least age 80Maintained until at least age 80 Slowing in central processing Slowing in central processing → Tasks take longer → Tasks take longer

to performto perform

Verbal skillsVerbal skills Maintained until age 70Maintained until age 70 Gradually ↓ in vocabulary, ↑ semantic errors and Gradually ↓ in vocabulary, ↑ semantic errors and

abnormal prosodyabnormal prosody

MentationMentation Difficulty learning, especially languages and Difficulty learning, especially languages and

forgetfulness in non-critical areas – doesn’t impair forgetfulness in non-critical areas – doesn’t impair recall of important memories or affect functionrecall of important memories or affect function

Peripheral Nervous SystemPeripheral Nervous System

↓ ↓ spinal motor neuronsspinal motor neurons

Nerve conduction slowsNerve conduction slows

↓ ↓ vibratory sensation – especially feetvibratory sensation – especially feet

↓ ↓ thermal sensitivity (warm-cool)thermal sensitivity (warm-cool)

↓ ↓ size of large myelinated fiberssize of large myelinated fibers

Musculoskeletal - MuscleMusculoskeletal - Muscle

↓ ↓ muscle fibers → ↓ muscle mass (sarcopenia) muscle fibers → ↓ muscle mass (sarcopenia)

→ lean body mass→ lean body mass

Infiltration of fat into muscle bundlesInfiltration of fat into muscle bundles

↑ ↑ FatigabilityFatigability

↓ ↓ Basal metabolic rate (4%/decade after age Basal metabolic rate (4%/decade after age

50)50)

Musculoskeletal - BoneMusculoskeletal - Bone

↓ ↓ Bone density – both trabecular and cortical boneBone density – both trabecular and cortical bone ↓ ↓ Osteoclast bone formationOsteoclast bone formation ↓ ↓ Bone remodellingBone remodelling ↑ ↑ adipocyte formation in bone marrowadipocyte formation in bone marrow Slower healing of fracturesSlower healing of fractures ↓ ↓ Vitamin D absorption → ↓ osteoblasts → ↓ bone Vitamin D absorption → ↓ osteoblasts → ↓ bone

formationformation ↑ ↑ Bone loss → Loss of height (stooping) and Dorsal Bone loss → Loss of height (stooping) and Dorsal

KyphosisKyphosis ↓ ↓ Bone density & microarchitectural bone deterioration Bone density & microarchitectural bone deterioration

→ Osteoporosis→ Osteoporosis

Musculoskeletal - JointsMusculoskeletal - Joints

Non-articular cartilage grows throughout life Non-articular cartilage grows throughout life

Articular cartilage does changeArticular cartilage does change ↓ ↓ thickness of cartilagethickness of cartilage ↓ ↓ chondrocytes chondrocytes Collagen becomes stiffer → Disordered Collagen becomes stiffer → Disordered

cartilage matrixcartilage matrix As a result, less able to handle mechanical As a result, less able to handle mechanical

stressstress

SkinSkin

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Skin - StructureSkin - Structure

Epidermal changesEpidermal changesMelanocytesMelanocytes

↓ ↓ 15%/decade15%/decade Density doubles on sun-exposed skinDensity doubles on sun-exposed skin ↑ ↑ lentigineslentigines

Langerhans cellsLangerhans cells ↓ ↓ densitydensity ↓ ↓ responsivenessresponsiveness

Dermal ChangesDermal Changes ↓ ↓ collagen – 1% annual decline, altered fiberscollagen – 1% annual decline, altered fibers ↓ ↓ densitydensity Progressive loss of elastic tissue in the papillary dermisProgressive loss of elastic tissue in the papillary dermis

Skin - FunctionSkin - FunctionPhysiologic DecrementPhysiologic Decrement Clinical Consequence (s)Clinical Consequence (s)

↓ ↓ Barrier functionBarrier function DrynessDryness

Slower Cell replacementSlower Cell replacement Rough surface Rough surface Delayed healingDelayed healing

Ineffective DNA repairIneffective DNA repair ↑ ↑ photocarcinogenesisphotocarcinogenesis

↓↓ ElasticityElasticity Lax skinLax skin

↓↓ Immunologic and Immunologic and inflammatory responsivenessinflammatory responsiveness

Chronic low-grade skin Chronic low-grade skin infectionsinfectionsInapparent injuries and infectionsInapparent injuries and infections

Skin – Function (Cont’d)Skin – Function (Cont’d)

Physiologic DecrementPhysiologic Decrement Clinical Consequence (s)Clinical Consequence (s)

Mechanical protection alteredMechanical protection altered↓↓ Sensory perceptionSensory perception

Frequent injuriesFrequent injuries

↓↓ SweatingSweating Tendency to hypothermiaTendency to hypothermia

↓↓ effectiveness of effectiveness of thermoregulation (vascular)thermoregulation (vascular)

Vulnerability to heat and coldVulnerability to heat and cold

↓ ↓ Vitamin D productionVitamin D production OsteomalaciaOsteomalacia

Impaired Wound healingImpaired Wound healing Persistent wounds, weak scarsPersistent wounds, weak scars

Immune systemImmune system ↓ ↓ Cell-Mediated immunityCell-Mediated immunity Lower affinity antibody productionLower affinity antibody production ↓ ↓ delayed-type hypersensitivitydelayed-type hypersensitivity ↑ ↑ Interferon-gamma, TGF-beta, TNF, IL-6, IL-1 production Interferon-gamma, TGF-beta, TNF, IL-6, IL-1 production

causing impaired macrophage functioncausing impaired macrophage function ↑ ↑ circulating IL-6circulating IL-6 ↓ ↓ IL-2 release and IL-2 responsivenessIL-2 release and IL-2 responsiveness ↓ ↓ production of B cells by bone marrowproduction of B cells by bone marrow

Resulting in ↓ immunity contributing to ↓ susceptibility to Resulting in ↓ immunity contributing to ↓ susceptibility to infections and malignancyinfections and malignancy

Sensory - VisionSensory - Vision

Yellowing of lensYellowing of lens

Impaired dark adaptationImpaired dark adaptation

Inability to focus on near items (Presbyopia)Inability to focus on near items (Presbyopia)

↓ ↓ Contrast sensitivity Contrast sensitivity

↓ ↓ Lacrimation → Dry eyesLacrimation → Dry eyes

Sensory – Smell and ThirstSensory – Smell and Thirst

SmellSmell

Detection Detection ↓ by 50%↓ by 50%

ThirstThirst

↓ ↓ thirst drivethirst drive

Impaired control of thirst by endorphinsImpaired control of thirst by endorphins

Sensory - AuditionSensory - Audition Bilateral loss of high frequency tonesBilateral loss of high frequency tones Thickened eardrumThickened eardrum Central processing deficitCentral processing deficit Difficulty discriminating source of soundDifficulty discriminating source of sound Impaired discrimination of target from Impaired discrimination of target from

noisenoise

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edicalim

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