Fisiologi Penuaan Dr Dian

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  • Physiology of AgingLaboratorium FisiologiFK UNEJ

  • Objectives

    Discuss the Characteristics of AgingReview the various Theories of AgingExplore the effects of Aging on the different organ systems

  • PenuaanDefinisi Menua => 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)


    Mortality increases exponentiallyBiochemical composition of tissue changesPhysiologic capacity decreasesAbility to maintain homeostasis diminishesSusceptibility and vulnerability to disease increases

    Environmental and Genetic factorsinfluence the rate of aging

  • THEORIES OF AGING: OXIDATIVE STRESSSynopsis: Oxygen converted during metabolism causes protein, lipid, and DNA damage over timeIn support: Mutations in oxidative stress pathway can extend life spanMutations in other pathways that increase longevity resist oxidative damageIn opposition: Antioxidants do not delay human senescence or disease

  • THEORIES OF AGING: IMMUNOLOGICSynopsis: 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


    Synopsis: Senescence results from activation or suppression of specific aging genes

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

    In opposition: Evolutionary pressures appear to select for reproductive fitness rather than senescenceLittle direct evidence of genetic programming of senescence in humans

  • Aging effects on organ systems

  • Cardiovascular

  • Cardiovascular: Structure

    Age-associated changePossible disease outcomes vascular intimal thickeningEarly stages of atherosclerosis

    vascular stiffnessSystolic HTNStrokeAtherosclerosis LV wall thickness early diastolic cardiac filling cardiac filling pressureLower threshold for dyspnea

    Left Atrial sizeLone Atrial Fibrillation

  • Cardiovascular: Function

    Age-associated changePossible disease outcomes

    Altered regulation of vascular toneVascular stiffeningHypertensionDecreased cardiovascular reserveLower threshold for and increased severity of heart failure

  • Pulmonary

  • Pulmonary - Structure Alveoli and lung capillaries Number and elasticity of parenchymal elastic fibers Gradual loss of elastic recoil of the lungsAirway size Ciliary action less effectiveChest wall stiffensRespiratory muscles weaken lung massDiaphragm weakens by 25%

  • Pulmonary - Function

  • Pulmonary Function FEV1 and FVC Residual volumeVentilation-Perfusion mismatching causes PaO2 [100 (0.32 * age)]Maximum inspiratory and expiratory pressures Diffusion of CO decreasedDecreased ventilatory response to hypercapnia

  • Renal

  • Renal - Structure Renovascular bed Renal Blood flowSelective loss of cortical vasculatureRenal mass 25% - mainly corticalRenal 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 changePossible disease outcomes liver size and blood flowImpaired clearance of drugs requiring phase I metabolism

    Impaired response to gastric mucosal injuryIncreased risk of gastric & duodenal ulcers pancreatic mass and enzyme reservesIncreased insulin resistance in effective colonic contractionsConstipation in gut-associated lymphoid tissueIncreased risk of gastric & duodenal ulcers

  • GI - Function

    Age-associated changePossible disease outcomes stomach acid productionAtrophic gastritis

    Impaired acid clearanceGERD

    Slowing of gastric emptyingProlong gastric distention meal-induced satiety Ca absorptionBone lossDelay in colonic transit rectal wall sensitivityConstipation tensile strength in smooth muscle of colonic wallDiverticulosis Insulin secretion Insulin resistance

  • EndocrineThyroid gland moderate atrophyOvarian failure T3 DHEA PTH GH, testosterone, estrogen Insulin secretion Impaired glucose tolerance

  • Hematology% of marrow space occupied by hematopoietic tissue declines stem cells in marrowSlowed erythropoiesis incorporation of iron into RBCAverage 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 plaquesAltered neurotransmitters

  • Central Nervous System - FunctionIntellectMaintained until at least age 80Slowing in central processing Tasks take longer to performVerbal skillsMaintained until age 70Gradually in vocabulary, semantic errors and abnormal prosodyMentationDifficulty learning, especially languages and forgetfulness in non-critical areas doesnt impair recall of important memories or affect function

  • Peripheral Nervous System spinal motor neuronsNerve conduction slows vibratory sensation especially feet thermal sensitivity (warm-cool) size of large myelinated fibers

  • Musculoskeletal - Muscle muscle fibers muscle mass (sarcopenia) lean body massInfiltration 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 - JointsNon-articular cartilage grows throughout life Articular cartilage does change thickness of cartilage chondrocytes Collagen becomes stiffer Disordered cartilage matrixAs a result, less able to handle mechanical stress

  • Skin

  • Skin - StructureEpidermal changesMelanocytes 15%/decadeDensity doubles on sun-exposed skin lentigines

    Langerhans cells density responsiveness

    Dermal Changes collagen 1% annual decline, altered fibers densityProgressive loss of elastic tissue in the papillary dermis

  • Skin - Function

    Physiologic DecrementClinical Consequence (s) Barrier functionDrynessSlower Cell replacementRough surface Delayed healingIneffective DNA repair photocarcinogenesis ElasticityLax skin Immunologic and inflammatory responsivenessChronic low-grade skin infectionsInapparent injuries and infections

  • Skin Function (Contd)

    Physiologic DecrementClinical Consequence (s)Mechanical protection altered Sensory perceptionFrequent injuries SweatingTendency to hypothermia effectiveness of thermoregulation (vascular)Vulnerability to heat and cold Vitamin D productionOsteomalaciaImpaired Wound healingPersistent wounds, weak scars

  • Immune system Cell-Mediated immunityLower 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 - VisionYellowing of lensImpaired dark adaptationInability to focus on near items (Presbyopia) Contrast sensitivity Lacrimation Dry eyes

  • Sensory Smell and ThirstSmellDetection by 50%

    Thirst thirst driveImpaired control of thirst by endorphins

  • Sensory - AuditionBilateral loss of high frequency tonesThickened eardrumCentral processing deficitDifficulty discriminating source of soundImpaired discrimination of target from noise

  • ****Key observations in support of the oxidative stress theory of aging:Free-radical damage to lipids, protein, and DNA has been found in aging heart, liver, and kidney tissue.Short-lived species accumulate this damage quickly.Transgenic animal models that concurrently overexpress copper and zinc superoxide dismutase (SOD) and catalase have extended life spans.Antioxidant compounds such as vitamin E can enhance the average life span in animal models. Interestingly, the expression of the human SOD gene in Drosophila neurons has been found to increase life span by 40%, which suggests that the central nervous system plays a key role in longevity.Caloric restriction, which extends life span, and single-gene mutations that increase longevity enhance resistance to oxidative stress in yeast, worms, flies, and rodents.Skeptics of the oxidative stress theory point out that knockout of the SOD gene does not accelerate aging. This observation attests to redundant systems that counter damage.**Epidemiologic studies of twins suggest that heritability of life span is between 22% and 33%. Similar studies in families yield a wider range of estimates, between 10