THE AGEING PROCESSTHE AGEING PROCESS

TERMINAL STATESTERMINAL STATES

Prof. M. Tatár, MD, PhDProf. M. Tatár, MD, PhD

Dept. of PathophysiologyDept. of Pathophysiology

GerontologyGerontology - - searching the biochemical searching the biochemical andand biological background of biological background of thethe ageing processageing process GeriatricsGeriatrics - - practical medical problems practical medical problems of the of the old peopleold people

Ageing process is a biologically determined Ageing process is a biologically determined phenomenon (phenomenon (primary ageingprimary ageing) ) influenced by influenced by hostile environmental factors (diseases, trauma, hostile environmental factors (diseases, trauma, socioeconomic state - socioeconomic state - secondary ageingsecondary ageing))

WHO:WHO:

- middle age: - middle age: (45 - 59 yrs)(45 - 59 yrs)

- presenium: - presenium: (60 - 74 yrs)(60 - 74 yrs)

- senium (old age): - senium (old age): (75 - 89 yrs)(75 - 89 yrs)

- very old age - very old age (90 and more (90 and more years)years)

Estimated population, proportion of population, and Estimated population, proportion of population, and growth ofgrowth ofpopulation above age 60 for the world and for selected population above age 60 for the world and for selected countries in 1970 and 1997 and projected for 2025countries in 1970 and 1997 and projected for 2025

0 20 40 60 80 100

100

50

0

1840

1900

1930

1980

% S

UR

VIV

ED

AGE IN YEARS

Deaths per 1000 women at ages 80 to 89 from 1950 to 1995Deaths per 1000 women at ages 80 to 89 from 1950 to 1995

JapanFranceSwedenU.K.U.S.A.

THE AGEING PROCESS - THE AGEING PROCESS - main characteristics from the medical main characteristics from the medical

pointpoint

• Increased mortality with age• Changes in biochemical composition in

tissues• Progressive deteriorative physiological

changes• decreased ability to respond adaptively

to environmental changes• increased vulnerability to many diseases

THEORIES OF AGEING 1THEORIES OF AGEING 1

I.I. Stochastic Stochastic theories consider ageing as a theories consider ageing as a tear tear and wear process and wear process at molecular, subcellular, at molecular, subcellular, cellular and organ level - what are the damaging cellular and organ level - what are the damaging agentsagents?? Somatic mutation theory and failure of DNA repair theory- - genes included in proteosynthesis overall deterioration of the precision of protein synthesis - genes for enzymes of the terminal oxidation localised in mitochondrial DNA (lack DNA repair mechanisms)Theory of random postsynthetic modification

- bioreactive forms of oxygen, nonenzymatic glycation- ability of defence mechanisms to prevent and repair random postsynthetic damage (accumulation of faulty molecules)

II. II. Genetic or pacemaker theories Genetic or pacemaker theories (ageing (ageing is a continuation of the development and is a continuation of the development and maturation). Ageing might be programmed by maturation). Ageing might be programmed by a genetic clocka genetic clock

1. Maximal life span of different species is constant 2. Normal cells growing in tissue culture are not able to divide indefinitely and their mitotic capacity decreases with the age of donor.

THEORIES OF AGEING 2THEORIES OF AGEING 2

Neuroendocrine theory claims that the hypothalamo-pituitary-adrenal axis is the main regulator of the ageing process

THEORIES OF AGEING 3THEORIES OF AGEING 3

The actual damage due to stochastic events depends to a great extent on the integrity and ability of the defence and repair mechanisms which are genetically coded and regulated

Reconciliation of the stochastic and genetic Reconciliation of the stochastic and genetic theoriestheories

TERMINAL STATES 1TERMINAL STATES 1

Tanatology:Tanatology: mechanisms of dying resulting in irreversible

disintegration of the organism as a whole 1.1. Preagonal stage - Preagonal stage - interaction of two interaction of two antagonisticantagonistic tendenciestendenciesa) damage resulting from pathological situations (ischemia, acidosis) developing especially in CNS b) defensive and compensatory reactions (tachypnoea, tachycardia, vasoconstriction) tending to counterbalance the impaired functions- exhaustion of compensatory reserves: preterminal apnoea, preautomatic pause followed by arrhythmias, progressive hypotension and tisue hypoperfusion

2. 2. Agonal stage:Agonal stage: chaotic function of various systems chaotic function of various systems escaped from cortical control; they are altered escaped from cortical control; they are altered byby subcortical regulatory centers and reflex subcortical regulatory centers and reflex mechanismsmechanismsa) Cheyne-Stokes breathing,

gaspingB) unconsciousness

3.3. Clinical death:Clinical death: coma, apnoea, pulslessnesscoma, apnoea, pulslessness

- prompt resuscitation attempts can sometimes result in full recovery

- progressive damage to most organs and systems

TERMINAL STATES 2TERMINAL STATES 2

4. Biological death - development of irreversible changes depends on the sensitivity of the organs to the lack of oxygen and nutrients supply

Brain deathBrain death

Clinical criteria: 1. Unresponsive coma2. No spontaneous respiration3. Absent cephalic reflexes, no ocular responses, fixed pupils4. Isoelectric EEG5. Absence of cerebral circulation

- irreversible brain damage, destruction- irreversible brain damage, destruction includes brainstem and cerebellumincludes brainstem and cerebellum

Cerebral death

- death of the cerebral hemispheres exclusive of the brainstem and cerebellum- individual is unable forever to respond behaviourally in any significant way to the environment- internal homeostasis is maintained (normal CVS, respiratory and GIT functions, normal temperature control)

Glasgow coma scale 1Glasgow coma scale 1

• Eye openingarousal mechanisms - reticular formation

• Verbal responsecognitive functions

• Motor response

Glasgow coma score 2Glasgow coma score 2

Eye opening

4 spontaneous3 to speach2 to pain1 none

Glasgow coma score 3Glasgow coma score 3

Verbal response

5 oriented

4 confused - converses but disoriented3 inappropriate words - no conversation 2 incomprehensible - no recognizable

words1 none (with pain stimuli)

Glasgow coma score 4Glasgow coma score 4

Motor response

6 obeys commands (if not, pain is applied)5 localises pain - tries to remove stimulus4 flexion withdrawal - no attempt to stop

stimulus 3 abnormal flexion - decorticate posture2 abnormal extension - decerebrate posture1 none, flaccide