AAging and the seniorsging and the seniors

K. BernáškováK. Bernášková

ContentContent

• What is aging?What is aging?• LifespanLifespan• Aging theoriesAging theories• Syndromes of premature agingSyndromes of premature aging• Changes due to agingChanges due to aging• How to prolong one’s life ?How to prolong one’s life ?• A senior as a patientA senior as a patient

What is aging ?What is aging ?

Complex biological process at the molecular, cellular and organ levels, which leads to progressive and inevitable (although gradual):

deterioration of all body functions

 loss of ability to adapt to stress

 increased risk of disease

structural changes

Changes occur over time and are not caused by disease or injury, and can eventually lead to death

LifespanLifespan

• Maximum lifespanMaximum lifespan

• Expected lifespanExpected lifespan == l life ife expectancyexpectancy

• AAverageverage lifespanlifespan

Maximum lifeMaximum life spanspan= maximum number of years a = maximum number of years a

member of a group has been member of a group has been observed to surviveobserved to survive

• fly fly

• tarantuletarantule

• horsehorse

• elephantelephant

• parrot parrot

• manman

320

4078

80122

Expected lifespanExpected lifespan = =

llife expectancyife expectancy = the expected age at death= the expected age at death

• a a statisticalstatistical measure of the average length of measure of the average length of

survivalsurvival • most often constructed as the life expectancy at most often constructed as the life expectancy at

birth for a given human population (according birth for a given human population (according

to to statistical tablets)statistical tablets)

• expected lifespan prolongs during yearsexpected lifespan prolongs during years

Life expectancyLife expectancy

menmen womenwomen 2001 (2008) 2001 (2008)2001 (2008) 2001 (2008)

SvedenSveden 77,1 77,1 (78,7) (78,7) 82,182,1 (84,2) (84,2) Austria Austria 76,176,1 (78,9) (78,9) 82,082,0 (83,6) (83,6) FranceFrance 75,275,2 ((72.3) 72.3) 82,882,8 (80.5)(80.5) Czech R.Czech R. 72,272,2 ( (73.4) 73.4) 78,478,4 ( (79.5)79.5)

2065 (86,5) 2065 (86,5) (91,0)(91,0)

PolPolandand 69,869,8 ((71.3) 71.3) 778,1 8,1 ( (79.8)79.8) Hungary Hungary 68,368,3 ((69.2) 69.2) 776,86,8 ( (77.4)77.4)

is is calculated separately for calculated separately for year, year, gender andgender and geographic locationgeographic location

menmen womenwomen 2001 (2008) 2001 (2008)

2001 (2008)2001 (2008)

• Sierra LeoneSierra Leone 3333 3535• NigerNigeriaia 3737 (46,4) (46,4) 4141 (47,3) (47,3)• MalawiMalawi 3737 (48,1) 3 (48,1) 388

(48,4)(48,4)• ZambiZambiaa 3838 (42,1) (42,1) 3939 (42,5) (42,5)• BotswanaBotswana 3939 (50,5) (50,5) 3939 (50,7) (50,7)

Life expectancyLife expectancy

Causes of life expectancy Causes of life expectancy differences between men and differences between men and

womenwomen• Genetic Genetic

– female genotypefemale genotype– male mortality during prenatal periodmale mortality during prenatal period

• HormonalHormonal– estrogens and lipid metabolismestrogens and lipid metabolism– androgens and immunityandrogens and immunity– androgens and behaviourandrogens and behaviour

• SocialSocial role role

AAverageverage lifespanlifespan

== average number of years, which is a newborn average number of years, which is a newborn

supposed to live by maintaining of supposed to live by maintaining of the the

contemporary mortality ratecontemporary mortality rate

Is influenced by:Is influenced by:

– environmentenvironment– diseases – (health care level)diseases – (health care level)– life-stylelife-style

The oldest human beingThe oldest human being

• Jeanne Louise CalmentJeanne Louise Calment reached the longest reached the longest confirmed lifespan in historyconfirmed lifespan in history

• 122 years and 164 days122 years and 164 days

• She died in She died in 1997 1997

• Her Her recommendationrecommendation: : olive oil, chocolate, port, olive oil, chocolate, port, smokingsmoking

Aging in animalsAging in animals

• wild animals do not age (under normal wild animals do not age (under normal

conditions) conditions)

• animals living with men may grow older animals living with men may grow older

(dog(dogss, cat, catss, horse, horsess))

• exception: exception: salmon,salmon, whale whale

Cat given contact lenses

| December 19, 2008 | staff reporter

A 15-year-old cat's eyesight has been restored by contact lenses.

Aging in animalsAging in animals

• wild animals do not age (under normal wild animals do not age (under normal

conditions) conditions)

• animals living with men may grow older animals living with men may grow older

(dog(dogss, cat, catss, horse, horsess))

• exception: exception: salmon,salmon, whale whale

Theories of agingTheories of aging

Earlier:Earlier:

punishment for punishment for ““godlessness godlessness ””

loss of humidity of the tissuesloss of humidity of the tissues

loss of body warmthloss of body warmth

Recent biological tRecent biological theories of heories of agingaging

Many types of tMany types of theoriesheories::

• SocialSocial (why) (why) • EvolutionaEvolutionary (why)ry (why)

• Physiological (how)Physiological (how)

SSystemic levelystemic level CCellular levelellular level MMolecular levelolecular level

Biological Ageing Theories

Evolutionary PhysiologicalSocial

Programmed Stochastic

Intrinsic timing

Chance events

EvolutionaEvolutionary theoriesry theories

1)1) „„Disposable Body TheoryDisposable Body Theory““Once an organism has produced viable Once an organism has produced viable offspring its body isoffspring its body is no longer needed, it then no longer needed, it then ages and dies.ages and dies.

2) 2) „„Antagonistic Pleiotropy TheoryAntagonistic Pleiotropy Theory““Certain genes maybe useful in early life but Certain genes maybe useful in early life but detrimental in later lifedetrimental in later life

3) 3) „ „Accumulation of Late Acting Error TheoryAccumulation of Late Acting Error Theory““ Late acting genes have not been removed becauseLate acting genes have not been removed because they act afterthey act after reproductionreproduction

All All physiologicalphysiological theories must theories must meetmeet basic requirements: basic requirements:

The process The process of „ageing“ of „ageing“ should beshould be

- - ubiquitous (in all cells)ubiquitous (in all cells)

- - harmfulharmful

- - progressiveprogressive

- - endogenousendogenous

Physiological tPhysiological theories of ageingheories of ageing

1) Systemic level- neuroendocrine

theory - immunologic theory- endocrine theory

2) Cellular level- free radicals- cross-link theory- “wear and tear”

3) (Mitochondrias)- free radicals

PhysiologicalPhysiological ttheories of agingheories of aging

4) Molecular level

- programmed theory (telomeres) - special genes

- theory of accumulaton of failures in DNA transcription and theory of somatic mutations

- FREE RADICALS

Which theory is the right Which theory is the right ONE ?ONE ?

• no one and all of themno one and all of them

• there are about 200 teories about there are about 200 teories about aging mechanismsaging mechanisms

Properties Properties of of agageeing cellsing cells::

slowslowerer division division

cchange in hange in cellular cellular metabolism (metabolism (decreased decreased basal basal

metabolic rate and slowing of all chemical reactions) metabolic rate and slowing of all chemical reactions)

change in cellchange in cellularular function ( function (productionproduction of non-of non-

physiological physiological proteins, cytokines, growth factors, etc.) proteins, cytokines, growth factors, etc.)

inability of apoptosisinability of apoptosis

decreased sensitivity of decreased sensitivity of all all receptorsreceptors

reduced ability to withstand oxygen free radicalsreduced ability to withstand oxygen free radicals

DNA instability, which may result in cancerous growthDNA instability, which may result in cancerous growth

Syndromes of premature agingSyndromes of premature aging

• Diseases characterized by Diseases characterized by symptoms of premature aging symptoms of premature aging = = progeriasprogerias

• Are progerias disease conditions or Are progerias disease conditions or a premature aging?a premature aging?

• Segmental progeriasSegmental progerias

Syndromes of premature ageing Syndromes of premature ageing 11

• Hutchinson-Gilford‘s syndrome:Hutchinson-Gilford‘s syndrome:

-- exceedingly rare disorderexceedingly rare disorder

- - (shortened telomeres) ? - (shortened telomeres) ? - mutations in the mutations in the lamin A genelamin A gene

- - first signs during 1st year of lifefirst signs during 1st year of life– growth deceleration, baldness, no growth deceleration, baldness, no

subcutaneous subcutaneous fat, wrinkles, salient fat, wrinkles, salient nose, receding nose, receding chin, stiff muscles chin, stiff muscles and articles and articles

– death from coronary artery disease is frequent death from coronary artery disease is frequent and may occur before 10 years of ageand may occur before 10 years of age

Differences between Hutchinson-Differences between Hutchinson-Gilford syndrome and Gilford syndrome and real real agageeing:ing:

• Men don’t develop prostate problems.Men don’t develop prostate problems.

• No increased risk of cancer or cataracts.No increased risk of cancer or cataracts.

• Despite the rapid development of Despite the rapid development of

atherosclerosis the high blood pressure is very atherosclerosis the high blood pressure is very

rare.rare.

• Diabetes is very rare.Diabetes is very rare.

• They don’t get Alzheimer’s disease or suffer They don’t get Alzheimer’s disease or suffer

mental mental degeneration.degeneration.

Syndromes of premature ageing Syndromes of premature ageing 22

• Werner‘s syndromeWerner‘s syndrome– helicase failurehelicase failure

– changes start in adults (around the 30th year)changes start in adults (around the 30th year)

– progressive wrinkles, „bird“ face, greying of progressive wrinkles, „bird“ face, greying of

hair, osteoporosis, muscle atrophyhair, osteoporosis, muscle atrophy

– tendency to diabetes, hypertension, cataract, tendency to diabetes, hypertension, cataract,

increased incidence to cancerincreased incidence to cancer

– death on average in 47 years from ICHSdeath on average in 47 years from ICHS

Werner‘s Werner‘s syndromesyndrome

(AK, 58)(AK, 58)

Differences between Differences between Werner‘sWerner‘s syndrome and syndrome and real real agageeing:ing:

• No increased tendency to No increased tendency to

neurodegenerationneurodegeneration

• In men no prostate problemsIn men no prostate problems

• No changes in immune systemNo changes in immune system

Syndromes of premature ageing Syndromes of premature ageing 33

• Cockayne’sCockayne’s syndrome syndrome – failure to repair DNA transcriptionfailure to repair DNA transcription

– first signs during 1st to 2nd year first signs during 1st to 2nd year

– cachectic dwarfismcachectic dwarfism (1 m), (1 m), early postnatal early postnatal contractures of the spine (kyphosis, contractures of the spine (kyphosis, scoliosis) and joints,scoliosis) and joints, fotosensitivity, mental fotosensitivity, mental retardation, progressive degeneration of retardation, progressive degeneration of CNS and retinaCNS and retina

– death at age around 7 yearsdeath at age around 7 years

Cockayne’sCockayne’s syndromesyndrome

(boy, 4 years)(boy, 4 years)

- No increased tendency to cancer

development

Syndromes of premature ageing 4Syndromes of premature ageing 4

• Dyskeratosis congenitaDyskeratosis congenita• rare hereditary diseaserare hereditary disease

– telomerase failure (failure of tissues with rapidly dividing telomerase failure (failure of tissues with rapidly dividing

cells)cells)

– first signs around the 10th year of lifefirst signs around the 10th year of life

– characterized by cutaneous pigmentationcharacterized by cutaneous pigmentation, dysgenesis of , dysgenesis of

nails, changes of mucous membranes (GIT), osteoporosis, nails, changes of mucous membranes (GIT), osteoporosis,

progressive bone marrow failure syndrome progressive bone marrow failure syndrome

(thrombocytopenia, anemia )(thrombocytopenia, anemia )

– high susceptibility to develope malignancies (skin and high susceptibility to develope malignancies (skin and

blood) blood)

– death death around the 16th year of lifearound the 16th year of life

Syndromes of premature ageing Syndromes of premature ageing 55

• Down‘s syndromeDown‘s syndrome (trisomy of the 21th (trisomy of the 21th chromosome – excess of hydroxyl radicals)chromosome – excess of hydroxyl radicals)

• Diabetes mellitusDiabetes mellitus (pentosidin linkages, (pentosidin linkages, cross link theory)cross link theory)

Changes due to healthy ageingChanges due to healthy ageing

Age groups in menAge groups in men(according to WHO)(according to WHO)

• Youth: Youth: 15-24 years15-24 years• Young adult: Young adult: untill 30untill 30• Mature adult: Mature adult: 31 - 4531 - 45• Middle age:Middle age: 46 - 6046 - 60• Older age: Older age: 61 - 7561 - 75• Old age : Old age : 76 - 9076 - 90• Very old age:Very old age: more than 90more than 90

Healthy ageingHealthy ageing

starts in the 3 decade of lifestarts in the 3 decade of life

does not restrict everyday life does not restrict everyday life

does not lead to immediate changes in does not lead to immediate changes in

physical statephysical state

increases the risk of occurence of disease increases the risk of occurence of disease

(including polymorbidity) and death(including polymorbidity) and death

The result of healthy aging is homeostenosis and increased fragility

HomeostenosisHomeostenosis

– means decreased homeostatic (functional) means decreased homeostatic (functional)

reserves of many organs reserves of many organs

– leads to easier activation of stress reactionleads to easier activation of stress reaction

– leads to earlier development of signs and leads to earlier development of signs and

symptoms of diseasessymptoms of diseases

Properties Properties of of agageeing cellsing cells::

slowslowerer division division

cchange in hange in cellular cellular metabolism (metabolism (decreased decreased basal basal

metabolic rate and slowing of all chemical reactions) metabolic rate and slowing of all chemical reactions)

change in cellchange in cellularular function ( function (productionproduction of non-of non-

physiological physiological proteins, cytokines, growth factors, etc.) proteins, cytokines, growth factors, etc.)

inability of apoptosisinability of apoptosis

decreased sensitivity of decreased sensitivity of all all receptorsreceptors

reduced ability to withstand oxygen free radicalsreduced ability to withstand oxygen free radicals

DNA instability, which may result in cancerous growthDNA instability, which may result in cancerous growth

Changes due to ageing 1Changes due to ageing 1Generally Generally • hydration of all tissues hydration of all tissues

• protein body mass (bones, muscles..)protein body mass (bones, muscles..)• percentage of body fatpercentage of body fat• basal metabolismbasal metabolism• elasticity of all tissues (elastin fibers)elasticity of all tissues (elastin fibers)• sensitivity of receptorssensitivity of receptors

Endocrine Endocrine systemsystem

• changed (mainly decreased) rate of changed (mainly decreased) rate of endocrine secretion: estrogenes, endocrine secretion: estrogenes, melatonin, testosterone, STH, thyroid melatonin, testosterone, STH, thyroid hormones, renin and aldosterone hormones, renin and aldosterone

• basal secretion of ADH and ANPbasal secretion of ADH and ANP• glucose tolerance failure glucose tolerance failure • secretion of active vitamin Dsecretion of active vitamin D

Changes due to ageing 2Changes due to ageing 2

Nervous system

• brain weight,brain weight, brain perfusion and ability to autoregulate it• psychosomatic activity• downgrade of righting reflexes, prolonged nerve conduction• fragmentation of sleep

Locomotor apparatus

• muscle and bone mass • changes in articular cartilages

Immune system

• involution of thymus• function of T lymphocytes • production of antibodies after exogenous activation • secretion of autoantibodies• increased secretion of cytokins (x IL2)increased secretion of cytokins (x IL2)

Changes due to ageing 3Changes due to ageing 3RespiratorRespiratory system y system

• rigidityrigidity (of chest and lungs) (of chest and lungs), , • vital capacity and forsed expiratory vital capacity and forsed expiratory

volume, volume, elasticity elasticity• changed ventilation/perfusion ratio changed ventilation/perfusion ratio • activity of the ciliary epitheliumactivity of the ciliary epithelium • irritability of the respiratory tract, but irritability of the respiratory tract, but

decreased efficiency of caughdecreased efficiency of caugh

CardiovascCardiovascular ular systemsystem

• elasticity and compliance of arterialelasticity and compliance of arterial walls walls (x (x atherosclerosisatherosclerosis) ) • sensitivity of baroreceptorssensitivity of baroreceptors automatismautomatism of SA nodeof SA node • heart complianceheart compliance• sensitivity to sensitivity to β adrenergic β adrenergic stimulationstimulation x T3x T3• cardiac outputcardiac output

Changes due to ageing 4Changes due to ageing 4

Skin Skin • amount of subcutaneous fatamount of subcutaneous fat• atrophy of sweat glands (atrophy of sweat glands ( dryness and dryness and

fragility of fragility of skin) skin) • synthesis of vitamin D precursorsynthesis of vitamin D precursorss

SightSight • Presbyopia (less effective Presbyopia (less effective accomodation)accomodation)• transparency of the lenstransparency of the lens• pupillary diameter (decreased visul pupillary diameter (decreased visul

acuity in darkness)acuity in darkness)

Hearing Hearing • presbyacusiapresbyacusia• increased sensitivity to loud soundsincreased sensitivity to loud sounds

Smell and Smell and tastetaste

• sensitivitysensitivity

PhotoageingPhotoageingAA 58 year old 58 year old

American Indian American Indian

female who spent female who spent

practically all of her practically all of her

time outdoorstime outdoors

AA 72 year old Tibetian 72 year old Tibetian

monk who spent monk who spent

practically all of his time practically all of his time

indoors away from the indoors away from the

sun.sun.  

Changes due to ageing 4Changes due to ageing 4

Skin Skin • amount of subcutaneous fatamount of subcutaneous fat• atrophy of sweat glands (atrophy of sweat glands ( dryness and dryness and

fragility of fragility of skin) skin) • synthesis of vitamin D precursorsynthesis of vitamin D precursorss

SightSight • Presbyopia (less effective Presbyopia (less effective accomodation)accomodation)• pupillary diameter (decreased visual pupillary diameter (decreased visual

acuity in darkness) acuity in darkness) • transparency of the lenstransparency of the lens

Hearing Hearing • presbyacusiapresbyacusia• increased sensitivity to loud soundsincreased sensitivity to loud sounds

Smell and Smell and tastetaste

• sensitivitysensitivity

What influences the quality and What influences the quality and length of life?length of life?

• Congenital dispositionsCongenital dispositions

• Nutrition and lifestyleNutrition and lifestyle

• Living environment (pollutions, irradiation)Living environment (pollutions, irradiation)

• Social aspects (culture, marriage, inSocial aspects (culture, marriage, incomecome))

• Medical care, hygieneMedical care, hygiene

• AntioxidantsAntioxidants

• Restriction of risk factorsRestriction of risk factors (sunbathing, (sunbathing, stresstres etc) etc)

How to prolong one’s life ?How to prolong one’s life ?

• Special longevity elixirsSpecial longevity elixirs• PlantsPlants

– mandragora, ginsengmandragora, ginseng

• Animal products:Animal products:– yolk, ...yolk, ... bathing in milk or virgin blood bathing in milk or virgin blood

• Water, electricity, magnetismWater, electricity, magnetism

• In the end of the 19th century more „scientific“ In the end of the 19th century more „scientific“ methods:methods:– injections of gonadal extract injections of gonadal extract – ““transplantation” of monkey glandstransplantation” of monkey glands– vasectomyvasectomy, sterilisation, sterilisation

How to prolong one’s life ?How to prolong one’s life ?

In the 20th century:In the 20th century:

• Yogurth (Mečnikov)Yogurth (Mečnikov)

• Healthy life style : Healthy life style :

sport and physical exercisesport and physical exercise

memory training (sudoku!)memory training (sudoku!)

• EustresEustres

How to prolong one’s life ?How to prolong one’s life ?

In the 20th In the 20th and 21 and 21 centurcenturiesies::

• „ „Youth hormones“Youth hormones“

- DHEA- DHEA

- melatonin- melatonin

- STH- STH• Dietary caloric restrictionDietary caloric restriction• Red wine (resweratrol)Red wine (resweratrol)• Drugs ? (Metformin, mTor downregulators,Drugs ? (Metformin, mTor downregulators,

…)…)

The seniorsThe seniors

In the seniorIn the senior organism:organism:

Each organ or system ages on its own Each organ or system ages on its own (undependently on other organs)(undependently on other organs)

– Older people differ much more one from Older people differ much more one from another than young peopleanother than young people

– There exist vulnerable organs or systems There exist vulnerable organs or systems which respond to different changes first which respond to different changes first

• brainbrain• lower urinary tract lower urinary tract • cardiovascular systemcardiovascular system• motor systemmotor system

Older patientOlder patient has atypical findings (first affected the most vulnerable organs)has atypical findings (first affected the most vulnerable organs)

• findings appear at earlier stages of findings appear at earlier stages of the diseasethe disease

• some pathological findings are normalsome pathological findings are normal

• has increased tendency to polymorbidityincreased tendency to polymorbidity

Main problems of older patients Main problems of older patients ((five Ifive I))

1. 1. IInstabilitynstability

2. 2. IImmobilitymmobility

3. 3. IIntelectual impairmentntelectual impairment

4. 4. IIatrogenic impairmentatrogenic impairment

5. 5. IInkontinencynkontinency

Literature:Literature:

• http://elegans.uky.edu/300/index.htmlhttp://elegans.uky.edu/300/index.html

• http://www.merck.com/mrkshared/http://www.merck.com/mrkshared/mm_geriatrics/contents.jspmm_geriatrics/contents.jsp