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GOOD MORNING
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AGEING AND ITS IMPLICATIONS
BY
DR.SHAZIA HUSSAIN
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Gerontology"referstothestudyofthe
biological aspectsofaging.
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What Is Aging?
Ageing isoneofthe most complex biological
processes, whosedefinition is intrinsicallyrelatedto
itsphenotype.
Ageing isdefined astheorganicprocessofgrowing
olderandshowingtheeffectsofincreasing age
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Ageing begins atthe momentofconception, involves
thedifferentiation and maturationoftheorganisms
and its cells, atsomevariablepoint intimeleadsto
theprogressivelossoffunctional capacitycharacteristicsofsenescence andends indeath.
Ageing is a universal, intrinsic,progressive and
deleteriousprocess.
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THEORIES OF AGEING
Mevdeve in an excellent review stated that there were more
than 300 theories of ageing and the number kept increasing
till date.
Evolutionarytheories Systemic theories
Molecularand cellulartheories
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EvolutionaryTheories of Aging
Becauseofthe species-specific natureofmammal aging,
scientiststurnedtoevolutionary mechanics in attemptstoexplain
agingobservations.
Thevariousevolutionarytheories are:
Mutation accumulationtheory
Disposablesoma theory
Antagonisticpleiotropy theory
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Medawars Hypothesis
PeterMedawar(1952) proposedthat age measuredrelativeto
ageoffirstreproductive capability was a factorintheevolution
process.
Adverseeffects (e.g. aging) thatoccurred well beyondpuberty
wouldhaverelativelylittle impactontheorganisms abilityto
reproduce andpropagate itsdesignrelativetothesameeffects
occurring at a youngerage.
Subsequenttheorists Williams, Kirkwood, andotherssuggested
that aging might be a sideeffectofsomedesignfeaturethat
created individual benefit inyoungeranimals.
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Mutation accumulationtheory
The mutation accumulationtheory is basedonMedawar's Hypothesis,
whichsuggeststhattheevolutionaryeffectofadverseeventsdeclines
followingthe age at which anorganism is initially capableofreproduction.
Althoughthere issubstantial agreementthatevolutionary impactofadverse
eventsdeclines with age,Medawarproposedthat itdeclinedtothepointofbeingnegligible.
Medawar'shypothesisprovided anexplanationfortheenormous
differences inlifespan betweendifferent mammalspecies bytracingthose
differencesto correspondingdifferences in ageofsexual maturity. Indeed,
ageofsexual maturity correlates moderately well withlifespan in
mammals.
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Dispos
able
so
matheory
In 1977, a statisticiannamedThomas Kirkwoodpublishedhis
disposablesoma theory ofaging. Kirkwoods idea wasthat
organismsonlyhave a limited amountofenergythathasto be
divided betweenreproductive activities andthe maintenanceofthenon-reproductive aspectsoftheorganism (soma). Aging is
theresultofnaturaldegradingprocessesthatresult in
accumulationofdamage butthedamage can berepaired bythe
organism attheexpenseofreproduction.
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Antagonistic pleiotropic theory Accordingtothe antagonisticpleiotropytheoryofageing,
naturalselectionhasfavouredgenes conferringshort-term
benefitstotheorganism atthe costofdeterioration inlaterlife.
The'disposablesoma'theoryexpressesthis as a life-history
strategy in whichsomatic maintenance is below thelevel
requiredtoprevent ageing,thusenablinghigherimmediate
fertility.
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Systemic theories
Neuroendocrinetheory
Immunologic theory
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Neuroendocrinetheory
Firstproposed byProfessorVladimirDilman and Ward DeanMD,this
theoryelaborateson wearandtearbyfocusingontheneuroendocrine
system. Thissystem is a complicatednetworkofbiochemicalsthatgovern
thereleaseofhormones which are altered bythe walnutsizedgland called
thehypothalamuslocated inthe brain. Thehypothalamus controlsvarious chain-reactionsto instructotherorgans
andglandstoreleasetheirhormonesetc. Thehypothalamus alsoresponds
tothe bodyhormonelevels as a guidetotheoverallhormonal activity.
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But as wegrow olderthehypothalamusloses itprecisionregulatoryability andthereceptors whichuptake individualhormones become
lesssensitivetothem. Accordingly, as we age,thesecretionofmany
hormonesdeclines andtheireffectiveness (comparedunittounit) is
alsoreducedduetothereceptorsdown-grading.
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Immunologicaltheory
Accordingtothistheory,programmeddecline inthefunctioningofthe
immunesystem leadsto incresed vulnerabilityto infectiousdiseasesthus
causing aging anddeath
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Molecularand cellulartheories
Errorcatastrophic theory
Freeradicaltheory
Wasteproducttheory
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Errorcatastrophic theory
According to this theory, damage to mechanisms that
synthesise proteins, results in faulty proteins, which
accumulate to a level that causes catastrophic damage to cells,
tissues and organs.
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The Free RadicalTheory
According to this theory, accumulated damage caused byoxygen radicals causes cells to stop functioning and eventuallyorgans also stop functioning. An oxygen free radical is a by-product of normal metabolism produced when cells turn foodand oxygen into energy. This free radical, in need of a mate,
takes an electron from another molecule, which in turnbecomes unstable. This chain reaction produces a series ofcom pounds, some of which are harmful. They damageproteins, membranes and nucleic acids, particularly DNA,organelles, etc. All these damages within the body caused by
oxygen free radicals causes ageing
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Wasteproducttheory
When cells divide, the quantity ofwaste material percell decreasesbecause the wastes are "diluted" by apportionment between thedaughters which result from the division. The quantity of waste
present in a symmetrically orasymmetrically dividing population ofcells is governedby a first-order non-linear differential equation. In
the derivation of the equation, it is assumed (a) that waste is createdat a rate which is either constant or proportional to the amount ofwaste already formed, (b) that waste is neither destroyed nortransported across cell walls, and (c) that the rate ofcell division atlarge values of time is inversely proportional to the amount ofwaste
per cell raised to a power. Relations among the parameters of the
differential equation specify conditions under which its solutionsrise to a critical value. If the amount of waste per cell given by asolution of the differential equation exceeds this value, it is assumedthat deleterious effectsbecome evident and that cell death follows
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Lipofuscin accumulation as an agingtheoryfocuseson maintaining apositive balanceofthesubstance. Theyellow-brownproductdoes
accumulate invarious cellsthrough aging. The increasing accumulationof
lipofuscin in cells,likeheart, muscle,nerve,ganglia andnerve cells
demarcates aging.
Lipofuscin accumulation canleadtovarious age-related illnesses. This
includesseverehealthpredicamentssuch asvisionloss, macular
degeneration, Batten, Alzheimers andParkinsonsdisease, chronic
obstructivepulmonarydisease, melanosis coli anddenervative atrophy and
manyothers.
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DNA damage in ageing
The DNA damagetheoryofagingproposesthat aging is a consequenceof
unrepaired DNA damage accumulation. Damage inthis context includes
chemicalreactionsthat mutate DNA and/orinterfere with DNA replication.
Although both mitochondrial andnuclearDNA damage can contributeto
aging,nuclearDNA isthe mainsubjectofthis analysis. NuclearDNAdamage can contributeto agingeither indirectly (by increasing apoptosisor
cellularsenescence) ordirectly (by increasing celldysfunction) .
Inhumans, DNA damageoccursfrequently and DNA repairprocesseshave
evolvedto compensate. On average, approximately 800 DNA lesionsoccur
perhourineach cell,
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In any cellsome DNA damage mayremaindespitethe actionofrepair
processes. The accumulationofunrepaired DNA damage is moreprevalent
in certaintypesofcells,particularly innon-replicatingorslowlyreplicating
cells, which cannotrelyon DNA repairmechanisms associated with DNA
replicationsuch asthose inthe brain,skeletal and cardiac muscle.
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Progeroid syndrome,(neonatal): A rare congenital condition
characterized bypoorgrowth, agedfacial appearance, andmentalretardation. Deathoccursusually by 6 yearsofage
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Werner`ssyndrome
Werner Syndrome ("Adultprogeria") is a veryrare, autosomal recessive
disordercharacterized bythe appearanceofpremature aging
Werner'ssyndrome more closelyresembles accelerated agingthan any
othersegmentalprogeria. Forthisreason, Wernersyndrome isoftenreferredto as a progeroid syndrome, as itpartly mimicsthesymptomsof
Progeria.
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Weber-Cockayne syndrome,orNeill-Dingwall Syndrome
Is a rare autosomal recessive congenitaldisordercharacterized by
growthfailure, impaireddevelopmentofthenervoussystem,
abnormalsensitivitytosunlight(photosensitivity), andpremature
aging. Hearingloss andeye abnormalities (pigmentaryretinopathy)areothercommonfeatures, butproblems with anyorallofthe
internalorgans arepossible. It is associated with a groupof
disorders calledleukodystrophies. Theunderlyingdisorderis a
defect in a DNA repairmechanism.
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Hutchinsonsgilfordsyndrome
Symptoms appearin infancy.
Premature ageing
Cellsfrom Hutchinson-Gilfordpatients appeartohavediminished
replicative capacity, butnotnearly asshort a lifespan as cellsfrom Werner
patients. Nevertheless,thegenetic and biochemical causesofprogeria remain
unknown.
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Telomeretheory
Telomeres are bitsofjunkDNA attheendofchromosomesthatprotect
real DNA everytime a celldivides. Whathappens isthat,theverylast bit
ofa chromosome cant be copied 100% - a little bitgets cutoff. It was
thoughtthat, as celldivide,thetelomeresgetshortereachtime,until,they
aregone. Atthatpoint,thereal DNA cannot be copied anymore andthecellsimply ages andnolongerreplicates.
Inpopulationlevelstudies,researchershaveshownthatolderpeoplehave
shortertelomeres. Eventually,the cells withshortertelomeres cannolonger
replicate and,takenovertime andlotsofcells,tissuedamage andthe
dreadedsignsofaging canshow up.
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Most cells canreplicate about 50 times beforethetelomeres aretooshort.
Some believethattelomeres arethesecrettolongevity andthere are
circumstances in whichthetelomeres willnotshorten
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Pathologic and Physiological
Age-Related Changes
Inhumans,somefunctionslikehearing andflexibility begintodeteriorateearly inlife,mostofourbody'sfunctionaldeclinetendsto begin afterthesexualpeak,roughly at age 19.
Aging is characterized by changes in appearance,such as a
Gradualreduction inheight and weightlossduetolossofmuscle and bone mass,
A lowermetabolic rate,
Longerreactiontimes,
Declines in certain memoryfunctions,
Declines insexual activity
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In women, Menopause,
A functionaldecline in audition,olfaction, andvision,
Declines inkidney,pulmonary, and immunefunctions,
Declines inexerciseperformance, and multipleendocrine changes.
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The incidenceofa numberofpathologies increases with age .
These includediabetes,heartdisease, cancer, arthritis, andkidneydisease.
The incidenceofsomepathologies,likesinusitis,remainsrelatively
constant with age, whilethatofothers,like asthma,evendecline.
Therefore, it is importanttostressthat aging isnot merely a collectionofdiseases. With age we become moresusceptibleto certaindiseases.
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Conclusion
Agingtheoryhas beentreated as an academic issue. Howeverit is
increasingly clearthatourapproachto age-relateddiseases could be
dramatically affected byourunderstandingofthe agingprocess and
thattherefore agingtheoryhas become apublic health issue. Efforts
shouldtherefore beexpendedtodefinitivelyresolvethetheory issues
anddevelopresearchfundingpolicy basedontheresults.
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Thankyou
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References
997 - 2001, 2004, 2005, 2008, 2010 by Pedro
de Magalhaes, Integrative Genomics of Ageing
Group.
Free radical research dec 2006
Williams, G.C. (1957). "Pleiotropy, natural
selection and the evolution of senescence"
(PDF). Evolution 11 (4): 398411.
doi:10.2307/2406060. JSTOR 2406060.
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Journal of Bioscience Hypotheses 2 (2): 5964.
doi:10.1016/j.bihy.2008.12.02
Robbins pathologic basis of diseases 7th,
edition
.