PHYSIOLOGY OF AGING

Dr Syed Shahid Habib

MBBS DSDM PGDCR FCPS
Professor & Consultant Clinical Neurophysiology
Dept. of Physiology
College of Medicine & KKUH
King Saud University
 Objectives
At the end of this session you should be
able to:
1. Define Aging and its consequences
2. Describe the theories of aging and
terms Used
3. Explain changes in different body
systems during Aging
4. Describe Important clinical conditions
5. Elaborate Geriatric syndrome
 AGING
Aging is the progressive, universal
decline first in functional reserve and
then in function that occurs in
organisms over time
Aging is not a disease; however, the risk of
developing disease is increased, often
dramatically, as a function of age.
Elderly ------ Age 65 to 74 Young old (65–74),
Aged -------- Age 75 to 84 The middle old (75–84)
Very Old ---- Age 85 and more Oldest old (85+)
 Aging is characterized by
• Changes in appearance (gradual reduction in height
and weight loss due to loss of muscle & bone mass)
• A lower metabolic rate
• Longer reaction times
• Declines in certain memory functions
• Declines in sexual activity and in women menopause
• A functional decline in audition, olfaction, and vision
• Declines in kidney, pulmonary, and immune functions,
declines in exercise performance, and multiple
endocrine changes

(Craik and Salthouse, 1992; Hayflick, 1994, pp. 137-186; Spence, 1995
 THE TERM AGEING
• UNIVERSAL AGEING: age changes that all
people share)
• PROBABILISTIC AGEING: age changes that
may happen to some (eg type two diabetes).
• CHRONOLOGICAL AGEING: referring to how
old a person is
• SOCIAL AGEING:society's expectations of
how people should act as they grow older
• BIOLOGICAL AGEING: an organism's
physical state as it ages
 Some Theories of Aging

Hypothesis How It May Work

Genetic Aging is a genetic program activated in post-
reproductive life when an individual's
evolutionary mission is accomplished
Oxidative stress Accumulation of oxidative damage to DNA,
proteins, and lipids interferes with normal
function and produces a decrease in stress
responses
Mitochondrial A common deletion in mitochondrial DNA
dysfunction with age compromises function and alters
cell metabolic processes and adaptability to
environmental change
 Some Theories of Aging

Hypothesis How It May Work

Hormonal changes The decline and loss of circadian rhythm in
secretion of some hormones produces a
functional hormone deficiency state
Telomere Aging is related to a decline in the ability of
shortening cells to replicate
Defective host The failure of the immune system to
defenses respond to infectious agents and the
overactivity of natural immunity create
vulnerability to Inf..
Accumulation of Renewing tissues become dysfunctional
senescent cells through loss of ability to renew
OXYGEN - free radicals (FR) and reactive oxygen species (ROS)

CELL METABOLISM ENVIRONMENT

INFECTION

LIFESTYLE
DNA damage

POLLUTION
DIET
 Mitochondria produce ROS:

Molecules damaged

The respiratory chain (resp. chain) produces superoxide radicals (O2-·), which generate
hydrogen peroxide (H2O2) and hydroxyl radicals (HO·). Mitochondrial nitric oxide synthase
(NOS) produces nitric oxide (NO·), which combines with O2-· to generate peroxinitrite
(ONOO-). All these ROS may cause mitochondrial and cellular damage if present in excess.
MPT, Mitochondrial permeability transition.
Kowaltowski 2002
Age-Related Physiological Changes
Three Groups of Systems Affected
Physiological Changes
• Cardiovascular system
1)Changes in autonomic • Respiratory System
functions and cellular
homeostasis e.g. temperature,
• Genitourinary System
blood volumes and Endocrine • Gastrointestinal System
changes • Endocrine System
• Skin and Musculoskeletal
2)Reduction in organic mass e.g. System
brain, liver, kidneys, bones and • Nervous System
muscles • Body temperature
regulation
3)Reduction in organic functional • Immune System
reserve e.g. lungs and heart • Psychological Changes

tmc 11
 AGING NERVOUS SYSTEM

“Use it or lose it!”

Individuals who remain mentally active perform better on
cognitive tasks than those who engage in mental activity less often
•Accelerated rate of brain shrinkage after age 50.
• Loss of 100,000 neurons in the cortex per day.
• Irreversible process of brain dysfunction.
 Nervous System
•Neuronal loss is normal in the aging brain but the
ability to learn remains generally unchanged
•There is loss of dendritic arborization
•Recall memory is affected more than cognitive
function in normal aging
•Lowered seizure threshold
•Reduced Sympathetic nervous system activity
•Reduced Neurotransmitter levels (Dopamine,
Serotonin, Glutamate
•Changes in sleep patterns
Intellectual functioning defined as “Stored”
•Increased risk of stroke memory increases with age
Problem solving skills increase with age
 Brief Geriatric Assessment
Instruments
Domain Instrument Comments
Cognition
Widely studied and
Dementia MMSE accepted
Timed time and change test Sensitive and quick
Sensitive and easy to
Delirium CAM apply
Affective disorders GDS 5-question form Rapid screen
Visual impairment Snellen chart Universally used
No special equipment
Hearing impairment Whispered voice needed
Can be performed by
Pure tone audiometry trained office staff
DENTALc
Dental health
Weight loss of >4.5 kg (>10 lb)
in 6 months or weight <45 kg
Nutritional status (<100 lb)
Requires no special
Gait and balance "Timed Get Up and Go" test equipment
 Aging nervous system

Structure Regional function

Basal ganglia Becomes bright in appearance due to iron
accumulation (movements affected)
Subarachnoid space Increase in size due to brain shrinkage

Hippocampus Reduction in size due to cell loss in the

structure.
Par of limbic system Involved in learning & long
term memory
Ventricles Increase in size due brain shrinkage.
White Matter Reduction in size due to neuronal atrophy in the
deep brain.
Involves in information transmission.
 Aging nervous system
Changes Consequences
• Decreased brain • Drug toxicities
weight • delirium
• Cerebral blood flow • Altered mood
• memory • Decreased IQ scores
• Alteration in CNS • “Benign senile
neurotransmitters forgetfulness”
• Decreased vibratory • Increased postural
sense • instability
• Altered gait
• Falls, accidents
 CONGITIVE CHANGES IN AGING:
MENTAL PROCESSING
DECLARATIVE MEMORY OR
EXPLICIT MEMORY
Decline in attentional ability EPISODIC MEMORY
(Events)
SEMANTIC MEMORY
(Words, language) Late to
HIPPOCAMPUS AND IS
ASSOCIATED WITH
CONSCIOUSNESS
SKILL MEMORY OR
IMPLICIT MEMORY
IT DOES NOT INVOLVE
AWARENESS.
↓Working memory INVOLVES
CEREBELLUM,
MOTOR CORTEX,
SENSORY CORTEX,
VISUAL AREAS

There is decline in mental processing via reduction of attentional ability and decline
in ability in forming working memory (mainly includes short term memory)
There is decline in explicit memory that involves hippocampus (surroudings &
Skills) and is associated with awareness & attention unlike implicit.
 Hearing
• Presbycusis: Part of normal
aging (35% people over 60 years of
age have bilateral, symmetric &
progressive impairment for high
pitched sounds sensorineyral
hearing loss)
• Cerumen impaction: is one of
the most common reversible
cause of condutive hearing loss in
elderly
Damage to the hair cells of the organ of Corti may be caused by intense noise, viral
infections, ototoxic drugs (e.g., salicylates, aminoglycoside antibiotics, furosemide
and chemotherapeutic agents such as cisplatin), fractures of the temporal bone,
meningitis, cochlear otosclerosis (see above), Ménière's disease and Aging
Loss of ability to see items
that are close up begins in Vision
the 40’s (Presbyopia)
Size of pupil grows smaller
with age: focusing becomes
less accurate
Pupil less sensitive to light
Opacaification of lens
(Cataract)
Lens of eye yellows making it
more difficult to see red and
green colors
Night vision not as acute
Arcus Senilis
 Disorders of the Sense of Taste
•Dorsum surface shows loss
of filiform papilla
•Foliate papillae more
prominent.
•Fissures increase
•Dryness of the mouth
•The ventral surface of the
tongue shows the presence of
nodular varicose enlargement
also known as caviar tongue
•Loss of taste buds with age
Sensory gustatory losses are caused by inflammatory and degenerative diseases in the
oral cavity; a vast number of drugs, such as antithyroid and antineoplastic agents;
radiation therapy to the oral cavity and pharynx; viral infections; endocrine disorders;
neoplasms; and aging
 Pain and Sense of Touch

• With age, skin is not as sensitive as in youth

– Contributing factors include:
1. Loss of elasticity
2. Loss of pigment
3. Reduced fat layer
• Safety Implications:
1. Lessened ability to recognize dangerous
levels of heat
2. Lessened ability of body to maintain
temperature
3. Tendency to develop bruises, skin tears more
easily
 SLEEP PATTERNS
• It tends to become more fragmented,
with more awakenings during the
night.
• Total sleep time stays the same or is
slightly decreased (6.5 to 7 hours per
night).
• The transition between sleep and
waking up is often abrupt, which
makes older people feel like they are a
lighter sleeper than when they were
younger.
• Three or four awakenings each night
• The proportion of slow wave sleep
decreases relative to total sleep time,
but the proportion of sleep that is
REM sleep ↓ or is unchanged
Geriatric Syndromes

• Dementia and Delirium

• Falls
• Urinary Incontinence
• Pressure Ulcers
• Functional Decline
 Dementia and Delirium
• Dementia is a syndrome of progressive
decline in which multiple intellectual
abilities deteriorate, causing both
cognitive and functional impairment.
• Delirium is an acute state of confusion
• Delirium may be the only manifestation of
a life-threatening illness in the older adult.
Infection
Drugs
 Alzheimer’s
Disease

• Alzheimer’s disease is defined as

premature aging of the brain, usually
beginning in mid-adult life and
progressing rapidly to extreme loss of
mental powers similar to that seen in
very, very old age.
 Alzheimer’s Disease
(Features)

(1) An amnesic type of memory impairment

(2) Deterioration of language
(3) Visuospatial deficits.

Motor and sensory abnormalities, gait

disturbances, and seizures are uncommon
until the late phases of the disease.
 Amyloid Plaques

• It is hallmark of Alzheimer's disease

• There is accumulation of amyloid plaques between
nerve cells (neurons) in the brain.
• Amyloid is a general term for protein fragments that
the body produces normally. Beta amyloid is a
protein fragment snipped from an amyloid precursor
protein (APP).
• In a healthy brain, these protein fragments are
broken down and eliminated. In Alzheimer's disease,
the fragments accumulate to form hard, insoluble
plaques.
 Neurofibrillary Tangles
• These are insoluble twisted fibers found
inside the brain's cells.
• Consist primarily of a protein called tau,
which forms part of a structure called a
microtubule. The microtubule helps transport
nutrients and other important substances
from one part of the nerve cell to another.
• In Alzheimer's disease, however, the tau
protein is abnormal and the microtubule
structures collapse.
Carotid sinus hypersensitivity

• Carotid sinus syncope occurs when there

is an exaggerated vagal response to
carotid sinus stimulation,
• Provoked by wearing a tight collar, looking
upwards or turning the head
• Carotid sinus syndrome occurs in the
elderly and mainly results in bradycardia.
• Most common etiologies of atrioventricular
block
• Do not massage both carotids
simultaneously.
 Control of
blood pressure

Short-term Long-term
Control control
(Rapid)

Baroreceptor Renal
reflex compensation
 Pressure on the carotid sinus,
produced by the
tight collar or carotid massage

can
cause
marked
bradycardia
vasodilatation
Fainting
or syncope