AGING CONCEPT AND
PATHOPHYSIOLOGY
Dr Ravi Soni
Senior Resident
DGMH, KGMU
LUCKNOW

Aging Concept
• Aging is a pattern of life changes that occurs
as one grows older.
• Gerontology is the study of individual and
collective aging processes
– Biological age
– Psychological age
– Social age
– Legal age
– Functional age

Normal Aging
 Who is old?
• Biological and psychological aging changes usually occur
gradually, over years or decades, and as a result, there is no
single age at which people in general can be said to be old.
• Commonly people older than 65 are called ‘OLD’
• Gerontologists often draw finer chronological demarcations:
• Young-old: <75
• Old-old: >75
• Oldest-old: >85

Cognitive Abilities in Later Life: A Processing
Resource Model
• Declines in three fundamental cognitive-processing
resources:
1. Processing Speed: reduced speed of information processing
and response- most predictable
2. Working Memory: refers to short-term retention and
manipulation of information held in conscious memory, a
type of “online” cognitive processing. exa. Examples include
consciously recalling a telephone number long enough to write it down
3. Sensory and Perceptual changes: decrements in visual and
auditory acuity and other perceptual changes.

Explanations of Cognitive Aging
Changes
• Neuropathological and neuroimaging studies: changes in brain with
aging
• generalized atrophic and white matter changes as well as region-
specific variations in the extent of cell loss
• Affected areas: Within the cortex, the prefrontal lobes are
disproportionately affected, Hippocampus and entorhinal cortex
are affected but data are conflictual
• Subcortical monoaminergic cell populations, are also subject to
prominent decline in aging
• Spared areas: Temporo-parietal association areas
• Areas in which there is relative sparing with age: the globus
pallidus, the paleocerebellum, the sensory cortices, and the pons

General Aging Trends

General Aging Trends

Factors That Influence Cognitive Aging

Personality and Emotional Changes
1. Coexisting Stability and Change:
• Developmental optimism: subjective growth in personality
2. Influences on Adult personality: three developmental
forces:
- Social clock
- grand adaptive strategy: individual’s desire for continuity
in personal past and present
- genetic factors: A study of elderly twins and multigenerational
families found a genetic contribution to negative affect but not to
positive affect
• Eriksonian Psychosocial developmental stages
• Late adulthood: integrity vs despair
• Virtue: wisdom

Personality and Emotional Changes
3. Personality and Perceptions of Health: Older adults’ perceptions
of their health have been linked to a variety of objective health
outcomes, including mortality
• Depression: affects subjective health concerns
• Neuroticism: is inversely associated with self-perceptions of good
health
• Extraversion: is positively associated
these associations were stronger among persons age 75 and older than among persons
in their 60s and early 70s (Duberstein et al. 2003)
4. Emotions, Coping, and Well-Being:
Emotions: old age is an emotionally rich and complex phase of life, and
the salience of emotion, increases in later years
have better control over emotions than do younger adults

Personality and Emotional Changes
• Coping: older people tend to cope with stressful events in different ways
• rely more on emotion-focused forms of coping, as opposed to active,
problem-solving approaches
• Emotion-focused coping is more
passive than confrontational,
individual than interpersonal, and
is oriented toward control of distressing feelings rather than toward
alteration of stressful situations
• Wellbeing: Specific stressful events have less of an effect on subjective
well-being in old age than does attainment of personal goals or the onset
of physical disability
• A model relates resilience in old age (i.e., maintaining adaptive behavior
in the face of stress and recovering from adversity) to a process of
selective optimization, in which goals are reshaped to fit current
limitations and environments, and resources are spared for personally
important activities that sustain self-esteem

Social Context of Aging
• Old age is accompanied by role change and, often, role loss
• expect transformations in occupational, family, and community
roles
1. Education, Work, and Financial Status
• Education: changes perception and thinking about life and health
• Work: lack of work, loss of income, continuous work help physically
as well as financially
• Financial status: retirement, loss of income
• Source of income: pension plans, social security, personal earnings, asset
incomes
2. Marriage and Widowhood:
3. Retirement and Grandparenthood:
4. Extended Families, Friends, and Group Involvement:

Biological Aging
• What is Aging?
• definition of aging was proposed by Birren and Zarit (1985):
“Biological aging, senescing, is the process of change in the organism,
which over time lowers the probability of survival and reduces the
physiological capacity for self-regulation, repair and adaptation to
environmental demands”
• Modern gerontologists distinguish
• Primary aging, which is postulated to reflect an intrinsic, presumably
genetically preprogrammed limit on cellular longevity,
• Secondary aging, which is due to the accumulated effects of
environmental insult, disease, and trauma.
• Primary aging seems to account for the relatively constant maximum life
span observed in almost all animal species studies,
• secondary aging explains much of the variability among individual
members of a species.

Theories of aging
• Aging theories can be divided into
• Organ-based,
• Physiological,
• Genomic hypotheses
• Organ-based theories hypothesize that human aging results from
incremental loss of organ function driven by the immune system or
alterations in neuro-endocrine function of the CNS.
• Physiological theories suggest that toxic levels of cellular waste products
accumulate over time resulting from free radical damage, incapacitation
of neuroprotective mechanisms, or cross-linkage of vital molecules, for
example, collagen, deoxyribonucleic acid (DNA), and vital proteins.

Genomic Hypothesis
• hypothesize aging as the consequence of somatic mutations,
multiple genetic errors, or programmed cell death
• Evidence that the “Hayflick phenomenon” is under genetic
control includes
1) a fair correlation between the doubling limit and the maximum species-specific life
span of the cell donor and
2) a reduced doubling limit in cells cultured from patients with genetic diseases of
accelerated aging
• The precise mechanism underlying the observed limits on normal cellular
division is not completely known, but several lines of evidence point to
telomeric shortening as at least one likely “clock” mechanism.
• A conceptual disagreement exists between theories that human senescent
brain alterations result from disuse versus overuse (i.e., the “use it or lose it”
theory) and those that attribute aging to cumulative damage (i.e., the
“wearing it out” theory)

PRIMARY AGING: STRUCTURAL
AND FUNCTIONAL CHANGES

Observed Changes in the Heart
• Deposits of the "aging pigment," lipofuscin accumulate.
• The valves of the heart thicken and become stiffer.
• The number of pacemaker cells decrease and fatty & fibrous
tissues increase around the SA node. These changes may result
in a slightly slower heart rate
• A slight increase in the size of the heart, especially the left
ventricle, is common. The heart wall thickens, so the amount of
blood that the chamber can hold may actually decrease.
• The heart may fill more slowly. To compensate, elderly subjects
demonstrate a doubling of percent atrial contribution to filling.

EFFECT OF CHANGES
• Under normal circumstances, the heart continues to
adequately supply all parts of the body. However, an
aging heart may be slightly less able to tolerate
increased workloads.
• Examples of stressors include: illness, infections,
emotional stress, injuries, and extreme physical
exertion.

Observed Changes in the Vessels
• Blood vessels
– Arteries
» thickening & stiffening in the media of large arteries is
though to be caused by collagen cross-linking
» smaller arteries may thicken/stiffen minimally; their
ability to dilate & constrict diminishes significantly
– Veins
» age-related changes are minimal and do not impede
normal functioning

Observed Changes in the Vessels
• The aorta becomes thicker, stiffer, and less flexible. This makes the blood
pressure higher resulting in LV hypertrophy.
• Increased large artery stiffness causes a fall in DBP, associated with a
continual rise in SBP. Higher SBP, left untreated, may accelerate large
artery stiffness and thus perpetuate a vicious cycle. Circulation. 1997;96:308-315
• Baroreceptors (stabilize BP during movement/activity) become less
sensitive with aging. This may contribute to the relatively common
finding of orthostatic hypotension.

Observed Hematologic Changes
• A decrease in total body water is observed with aging. Blood
volume therefore decreases.
• The number of red blood cells are reduced, but not
significantly.
• Most of the white blood cells stay at the same levels, but
lymphocytes decrease in number and effectiveness.

Observed Hematologic Changes
• Overall, cell counts and parameters in the
peripheral blood are not significantly different
from in young adult life.
• However, the cellularity of the bone marrow
decreases moderately. For example, 30%
cellularity on an iliac crest biopsy (which would be
very low for a young adult) is not unusual in an
older person.

The Immune System

Age and the Immune System
• The efficiency of the immune system declines with age, but this is
variable among persons.
• Nonspecific defenses become less effective
• The ability of the body to make antibodies diminishes.
• Autoimmune disorders are increased in older adults. Not everyone
believes that the increased incidence of autoimmune disease is an
expected part of aging.
– but all acknowledge the increase in findings of positive rheumatoid factor,
anti-nuclear antibody, and false-positive syphilis screens in healthy older
adults.
• The thymus gland (which produces hormones that activate T cells)
atrophies throughout life.
• The peripheral T-cells (J. Immunol. 144: 3569, 1990) proliferate much less exuberantly in
old age.

The Result….
• Common infections are often more severe
with slower recovery & decreased chances
of developing adequate immunity.

Take a Deep Breath…….

Observed Changes in the Lungs
• The number of cilia & their level of activity is
reduced.
• Glandular cells in large airways are reduced.
• Decreased number of nerve endings in larynx.
• The cough reflex is blunted thus decreasing the
effectiveness of cough.
• Decreased levels of secretory IgA in nose & lungs 
decreased ability to neutralize viruses.
• The number of alveoli do not change significantly.

Observed Changes in the Lung
• The number of FUNCTIONAL alveoli decreases
as the alveolar walls become thin, the aveoli
enlarge, are less elastic.
• Decreased elasticity of the lungs may be due
to collagen cross-linking.
• The loss of elasticity accounts for "senile
hyperinflation"; unlike in smokers, there is
little or no destruction of the alveoli.

Observed Changes in the Lungs
• Combine less functional alveoli with slightly
thickened capillaries  decreased surface
area available for O2-CO2 exchange  lower O2
to supply vital organs, especially in setting of
acute respiratory illness.

Observed Changes in the Lungs
• The respiratory muscles lose strength &
endurance.
• There is increased stiffness of chest wall (ie,
decreased compliance).
• Pulmonary vasculature becomes less elastic,
pulmonary artery thickens & enlarges 
increased resistance to blood flow in lungs
 increased pulmonary artery pressure.

Another Breather…..

Observed Changes in the Kidney
• Renal blood vessels become smaller & thicker
reducing renal blood flow.
• Decreased renal blood flow from about 600ml/min
(age 40) to about 300ml/min (age 80)
• Kidney size decreases by 20-30% by age 90.
– This loss occurs primarily in the cortex where the
glomeruli (# of gloms decrease by 30-40% by age 80) are
located.
• Decreased GFR. Typically begins to decline at
about age 40. By age 75 GFR may be about 50%
less than young adult. Current research shows
that this is not true for all elders, however.

Observed Changes in the Kidney
• There is a decline in the number of renal tubular
cells, an increase in tubular diverticula, & a
thickening of the tubular walls  decreased ability
to concentrate urine & clear drugs from the body.
• Overall kidney function, however, remains normal
unless there is excessive stress on the system.

The Bladder & Such….

Observed Changes in the Bladder & Such….
• The muscular ureters, urethra, & bladder
lose tone & elasticity. The bladder may
retain urine.
– This causes incomplete emptying.
• Decline in bladder capacity from about 500-
600mL to about 250ml  less urine can be
stored in the bladder.
– This causes more frequent urination.
– The warning period between the urge and
actual urination is shortened or lost as one ages.

Let’s see Those Muscles!!!

Observed Changes in the Musculoskeletal
System…..
• Muscles
– Sarcopenia (↓ muscle mass & contractile force) occurs
with age. Some of this muscle-wasting is due to
diminished growth hormone production (NEJM 323: 1, 1990),
– exactly how much is due to aging versus disuse is unclear.
– Sarcopenia is associated with increased fatigue & risk of
falling (so may compromise ADLs).
– Sarcopenia affects all muscles including, for example, the
respiratory muscles (↓ efficiency of breathing) & GI tract
(constipation).

Observed Changes in the Musculoskeletal
System…..
• Bone/Tendons/Ligaments
– Gradual loss of bone mass (bone resorption > bone
formation) starting around age 30s.
– Decreased water content in cartilage
• the “wear-&-tear” theory regarding cartilage destruction &
activity doesn’t hold up as osteoarthritis is also frequently seen in
sedentary elders.
– Decreased water in the cartilage of the intervertebral discs
results in a ↓ in compressibility and flexibility. This may
be one reason for loss of height.
– There is also some decrease in water content of tendons &
ligaments contributing to ↓ mobility.

Yummy, Yummy, in my Tummy…

Observed Changes in the GI Tract
• Some sources claim that one can expect atrophy & decrease in the number of
(especially) anterior (salty/sweet) taste buds, but this is controversial NEJM 322: 438, 1990
• Basal and maximal stomach acid production diminish sharply in old age. At the
same time, the mucosa thins. Very little seems to happen to the small bowel (J. Clin. Path.
45: 450, 1992)
• Decline in number of gastric cells  decreased production HCL (an acidic
environment is necessary for the release of vitamin B12 from food sources)
• Decrease in amount of pancreatic enzymes without appreciable changes in fat,
CHO, or protein digestion.
• Diminished gastric (eg pepsinogen) & pancreatic enzymes result in a hinderance to
the absorption of other nutrients like iron, calcium, & folic acid.
• Hepatic blood flow, size & weight decrease with age. Overall function, however,
is preserved, but may be less efficient in the setting of drug overload.
• Decreased tone in stomach & intestines result in slower peristalsis  constipation.

Hmmm….The Nervous System

Observed Neurologic Changes
• There is neuronal loss in the brain throughout life (the amount &
location varies). J. Ger. 47: B26, 1992.
– Loss is chiefly gray matter not white matter
– there is some evidence that although some neuronal loss occurs with
age, many neurons have ↑ dendrite growth which may (at least
partially) compensate for neuronal loss in some areas of the brain.
• Slowed neuronal transmission
• Loss of brain weight and volume in most studies
• Loss of dendritic arbor, with reduced interneuronal connectivity
• Interneuronal accumulation of lipofuscin and loss of organelles
• Neurofibrillary degeneration of neurons; accumulation of senile
plaques, especially in hippocampus, amygdala, and frontal cortex

Observed Neurologic Changes
• The lens of the eye loses fluid and becomes less
flexible, making it more difficult to focus at the near
range.
• Dry eyes
• Changes in sleep cycle: takes longer to fall asleep,
total time spent sleeping is less than their younger
years, awakenings throughout the night, increase in
frequency of daytime naps
• Sense of smell markedly decreases

Neurobiology of aging

Neurobiology of aging

Observed Hair Changes
– Men:
• men loose the hair about their temples during their 20s
• hairline recedes or male pattern baldness may occur
• increased hair growth in ears, nostrils, & on eyebrows
• loss of body hair
– Women
• Usually do not bald, but may experience a receding hairline
• hair becomes thinner
• Increased hair growth about chin & around lips
• loss of body hair

Observed Toenail Changes
– Become thicker & more difficult to cut
– Grow more slowly
– May have a yellowish color

Observed Skin Changes - Epidermis
• The number of epidermal cells decreases by
10% per decade and they divide more slowly
making the skin less able to repair itself
quickly.
• Epidermal cells become thinner making the
skin look noticeably thinner.
• Changes in the epidermis allows more fluid
to escape the skin.

In Between
• The rete-ridges of the dermal-epidermal
junction flatten out
– making the skin more fragile and making it easier
for the skin to shear.
– This process also decreases the amount of
nutrients available to the epidermis by decreasing
the surface area in contact with the dermis.
= slower repair/turnover

Observed Skin Changes - Dermis
These changes cause the skin to wrinkle and sag.
• The dermal layer thins
• Less collagen is produced
• The elastin fibers that provide elasticity wear
out.
---------
• ↓ function of sebaceous & sweat glands
contribute to dry skin

Observed Skin Changes – SubQ
• The fat cells get smaller
– This leads to more noticeable wrinkles and
sagging

Endocrine Changes

Endocrine System
• Because the endocrine system is so complex &
interrelated it is difficult to discern the effects
of aging on specific glands

Age-Related Changes in the Endocrine
System
• In most glands there is some atrophy &
decreased secretion with age, but the clinical
implications of this are not known.
• What may be different is hormonal action.

Age-Related Changes in the Endocrine
System
Hormonal alterations are variable & gender-
dependent
• Most apparent in:
– glucose homeostasis
– reproductive function
– calcium metabolism
• Subtle in:
– adrenal function
– thyroid function

Age-Related Changes in the Reproductive
System
Women
• The “climacteric” occurs (defined as the period during with reproductive capacity
decreases (ie, ovarian failure) then finally stops = loss of estrogen & progesterone;
FSH & LH ↑↑). This is also described as the transition from perimenopause (~age
40s) to menopause.
• thinning & graying of pubic hair
• loss of subQ fat in external genitalia giving them a shrunken appearance
• ovaries & uterus decreases in size & weight
• skin is less elastic + loss of glandular tissue gives breasts a sagging appearance
• other physical changes may include hot flashes (can cause sleep deprivation if they
occur at night), sweats, irritability, depression, headaches, myalgias. Sexual desire is
variable. The symptoms are typically present for about 5 years
• atrophy of vaginal tissues due to low estrogen levels = thinning & dryness occurs;

Age-Related Changes in the Reproductive
System
Men
• Testosterone decreases, testes become softer & smaller
• Erections are less firm & often require direct stimulation to
retain rigidity
• Though fewer viable sperm are produced & their motility
decreases, men continue to produce enough viable sperm to
fertilize ova well into older age.
• Less seminal fluid may be ejaculated
• they may not experience orgasms every time they have sex
• the prostate gland enlarges; this often results in compression
of the urethra which may inhibit the flow of urine.

Stay Active…..

Integrity vs despair
• Psychosocial
Conflict: Integrity versus
despair
• Major Question: "Did I
live a meaningful life?“
• Basic Virtue: Wisdom
• Important
Event(s): Reflecting back
on life
• Integrity: the state of
being whole and
undivided
• Despair: the complete
loss or absence of hope
• This stage occurs during late
adulthood from age 65 through the
end of life.
• During this period of time, people
reflect back on the life they have
lived and come away with either a
sense of fulfillment from a life well
lived or a sense of regret and
despair over a life misspent.

THE END
“healthy children will not fear life if
their elders have integrity enough not to fear
death.”