Ageing and Its Implications

8/3/2019 Ageing and Its Implications

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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

.

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