Introduction To Biology and Clinical Problems of Aging

Introduction:
Biology and Clinical

Problems of Aging
Orapitchaya Krairit, MD
Chief of Division of Geriatric Medicine
Department of Internal Medicine
Learning Objectives
Be able to describe:
• The major theories of how aging occurs
• The effects of aging on major organ systems
• How changes that occur with aging contribute to a systems-

wide dysregulation
• Normal age-related changes of the teeth, gums, and salivary
glands
• Common medical considerations in dental treatment
Copyright © 2018 American Geriatrics Society

Introduction and Definition of Aging
The biology of aging-1
The biology of aging involves studying:
• The “why” of aging (evolutionary theories)
• The “how” of aging (physiologic theories)
• The “what and where” of aging (molecular, cellular, and
organ system changes)
Theories of aging
1. Reflect our current understanding of the individual
maintenance pathways and homeostatic mechanisms
2. Provide pathways for investigating interventions that
modify aging
Functional capacity is a direct measure of the ability of cells, tissues,
and organ systems to function optimally and is influenced by both
genes and environment
Aging is the progressive decline and deterioration of functional
properties at the cellular, tissue, and organ level that lead to a loss of
homeostasis, decreased ability to adapt to internal or external stimuli,
and increased vulnerability to disease and mortality
Biologic age, based on an individual’s functional capacity, is the
metric for the biology of aging
Functional capacity + Aging Process = Biological Age

The rate and extent of aging varies both between individuals
and within an individual (e.g., asymmetric changes in vision,
hearing)
The most visible imprints of aging are:
• Loss of hair and pigmentation of hair
• Diminished height and muscle and bone mass
• Increasingly wrinkled, thinned skin
These progressive changes have a biologic basis in

altered molecular and cellular structure and function
Normal Aging versus Age-Related Pathologies
NORMAL AGING VS. AGE-RELATED PATHOLOGIES
• Normal aging involves cumulative diminution in molecular and
cellular properties and processes that exhibit physiologic
effects only when internal or external stressors, or both, perturb
homeostasis
• In pathology, or disease, compromised function is evident in
the resting (non-stressed) state
• There is a greater incidence of certain pathologies with
increasing age, such as diabetes, atherosclerosis,
hypertension, cancer, coronary heart disease, stroke,
osteoporosis, Alzheimer disease, and many others

Complexity, Homeostenosis,
and Integrated Systems and Aging
COMPLEXITY AND HOMEOSTENOSIS
• The complexity in the dynamics of interacting physiologic
systems decreases with age, resulting in a loss of robust and
integrated homeostasis
• Homeostenosis = The narrowing of reserve capacity that

underlies a decreased ability to maintain homeostasis under
stress
➢ Examples: body temperature maintenance, malnutrition

Homeostenosis
INTEGRATED SYSTEMS AND AGING
• The many biologic changes of aging affect multiple systems,
tending to strain the body’s homeostasis and the person’s
functional capacity
• It is imperative to acknowledge age- related physiologic
changes in the context of person-centered care

Dimension of age-related changes
Organ System Changes with Aging
การเปลี่ยนแปลงลักษณะภายนอก
Affected Organ or Physiologic Change Clinical
System Manifestations
Body composition ↓ Lean body mass Changes in drug

↓ Muscular mass levels
↓ Creatinine ↓ Strength
production Tendency toward
↓ Skeletal mass dehydration
↓ Total body water
↑ Percentage
adipose tissue
(until age 60,
then ↓until death)
DERMATOLOGIC CHANGES WITH AGING
• Epidermal and dermal changes
• Reduced lipids
• Slower wound healing
• Lower immune function
• Reduced collagen
• Hair changes
EPIDERMAL AGING
• In youth, epidermis interdigitates with dermis
• With aging, the interdigitations flatten, resulting in:

➢ Reduced contact between epidermis and dermis
➢ Decreased nutrient transfer
➢ Increased skin fragility
➢ Easy bruising

LIPIDS AND AGING
Aging is associated with decreased lipids in the top

skin layer, which leads to:
• Dryness and roughness

• Decreased barrier function

IMPAIRED HEALING AND IMMUNE FUNCTION WITH AGING
• Slower turnover of epidermal cells may account for

slower rate of wound healing
• Lower number of immune antigen-presenting cells

(such as Langerhans) may cause reduced cutaneous
immune surveillance

CHANGES IN THE AGING DERMIS
• Decrease in ground substance leads to wrinkling, atrophy
• Decreases in collagen and elastin cause haphazard,

fragmented fiber orientation and reduced skin elasticity

AGING SKIN AND HAIR
• Changes in follicular melanocytes cause graying hair
• Shortened duration of anagen (growth phase of hair

follicle) and increased duration of telogen (resting
phase) results in decreased hair density

Musculoskeletal System
• Sarcopenia = Age-related loss of muscle mass and strength
• Progressive decline in osteoblast number and activity but
osteoclasts remain unchanged with age → decline in bone
mass ~ 0.5 % per year in healthy older people
– Age-related changes in women →Menopausal changes in bone mass
and function
Sensory System
Affected Organ or System Physiologic Change Clinical Manifestations
Eyes ↓ Lens flexibility Presbyopia

↑ Time for pupillary reflexes ↑ Glare and difficulty adjusting
(constriction, dilation) to changes in lighting
↑ Incidence of cataracts ↓ Visual acuity
Ears Loss of high-frequency hearing ↓ Ability to recognize speech
Nose ↓ Smell ↓ Taste and

consequent ↓appetite
↑ Likelihood (slightly) of
nosebleeds
Taste buds ↓ Neurophysiologic responses of Decreased taste sensitivity
individual papillae No change in gustatory acuity
↓Number of taste buds
The Aging Brain: Summary
Neurological System
Affected Organ or Physiologic Change Clinical Manifestations
System
CNS ↓ Number of dopamine Tendency toward
receptors parkinsonian symptoms
↑ α-Adrenergic responses (e.g., ↑ muscle tone, ↓ arm
↑ Muscarinic parasympathetic responses swing)
Peripheral nervous system ↓ Baroreflex responses Tendency toward syncope

↓ β-Adrenergic responsiveness and number of ↓ Response to β-blockers
receptors Exaggerated response to
↓ Signal transduction anticholinergic drugs
↓ Muscarinic parasympathetic responses
Preserved α-adrenergic responses
การนอนหลับเมื่อสูงวัย
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33
PRINCIPAL EFFECTS OF AGING ON THE
CARDIOVASCULAR SYSTEM (1 of 2)
Age effect Clinical implication

↑ Arterial stiffness ↑ Afterload and systolic BP
↓ Myocardial relaxation & ↑ Risk of diastolic heart failure and

compliance atrial fibrillation
Impaired responsiveness to ↓ Maximum cardiac output; impaired
β-adrenergic stimulation thermoregulation
↓ Sinus node function and ↑ Risk of sick sinus syndrome, left
conduction velocity in the anterior fascicular block, and
atrioventricular node and bundle branch block
infranodal conduction
system

PRINCIPAL EFFECTS OF AGING ON THE
34
CARDIOVASCULAR SYSTEM (2 of 2)
Age effect Clinical implication

Impaired endothelium- ↑ Demand ischemia and risk of
dependent vasodilation coronary artery disease and
peripheral arterial disease
↓ Baroreceptor ↑ Risk of orthostatic hypotension
responsiveness
↓ Exercise response ↓ Exercise capacity and ↑ cardiac
(↓ maximal heart rate, complications (ischemia, heart
maximal cardiac output, failure, shock, arrhythmias, death)
VO2 max, coronary blood with illness
flow, peripheral
vasodilation)

35
CLINICAL EFFECTS OF CV CHANGES
• In healthy older adults, age-related changes

have modest clinically relevant effects on cardiac
hemodynamics and performance at rest
➢ Resting heart rate, ejection fraction, stroke volume,
and cardiac output are well preserved even at very
advanced age
• Ability to respond to increased demands
associated with exercise or illness (either cardiac
or noncardiac) declines progressively with
advancing age
➢ Peak aerobic capacity declines inexorably with age
39
AG E - R E L AT E D
P U L M O N A RY C H A N G ES
• Reduced airway size
• Shallow alveolar sacs
• Reduced chest wall compliance
• Intercostal muscle atrophy
• Reduction in diaphragmatic strength by 25%

Respiratory System
 Loss of elastic tissue → Enlarged Alveolar ducts →
Decreased surface area for gas exchange→ Increased
anatomic dead space
 Closed area in dependent portions of the older lung
during all or part of the respiratory cycle → Declining
arterial P02 with age →Increased A-a gradient
Pao2 = 109 - (0.43 X age)

Respiratory System
 Decreased central and peripheral drive to the
respiratory muscles → Decreased responses to
hypoxemia, hypercapnia, and mechanical loading
 Decreased respiratory muscle strength and greater
closing volumes → less vigorous cough
 Slower and less effective mucociliary clearance → ↓
Clearance from large airways and clearance of inhaled
particles from the small conducting airways
D I F F I C U LT I ES I N R ECO G N I Z I N G 47
R ES P I R ATO RY SY M P TO M S
• A common misperception is that older people tend to

overestimate or exaggerate respiratory symptoms
—the opposite is more often true
• Older people often have more than one cause of their

problems
➢ Dyspnea, cough, and wheezing may overlap
➢ The causes may include a combination of diseases
such as asthma or emphysema, obstructive sleep
apnea, heart failure, and GERD

Gastrointestinal Tract
Physiologic changes Results
•Thin epithelial lining of oral mucosa Predisposing older persons to root
•Receded gums and exposing the caries and incomplete mastication
tooth cementum
•Altered transfer of the food bolus to •Less effective mastication
the pharynx •Decreased food clearance from the
•Loss of esophageal muscle pharynx
compliance
•Increased aspiration risk in older
adults
•Decreased prostaglandin synthesis •Increased rates of gastritis and
•Decreased bicarbonate and increased sensitivity to gastric irritants
nonparietal fluid secretion
•↓Number and volume of the •Delayed gastric emptying

interstitial cells of cajal bodies
•↓G astric blood flow
•↓Sensory neural function
Gastrointestinal Tract
Physiologic changes Results
↓ Myenteric plexus neurons and a Reduced colonic propulsive motility

decline in the interstitial cells of Cajal
Decreased liver mass, and perfusion Decrease Cytochrome P450 content

and blood flow → Slower metabolic clearance of
many drugs ~ 20 to 40%
Age-related decreased synthesis of Lower amounts of vitamin K

vitamin-K-dependent clotting factors antagonists needed to anticoagulate
Renal System
Renal System
Immune System
• Immunosenescence = The aging of the immune
system
–↓ The ability of lymphocytes (both B and T cells) to work in
concert to generate effective immune responses upon
exposure to new antigens, in the form of either infections
or vaccinations
Affected System Physiologic Clinical Manifestations
Change
Immune system ↓ T-cell function Tendency toward some infections and
↓ B-cell function possibly cancer
↓ Antibody response to immunization or
infection but ↑Autoantibodies
ระบบภูมคิ ุ้มกัน
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H O M EO STAT I C R EG U L AT I O N
• Impaired in many endocrine systems with aging
• Loss of function in one aspect of endocrine

function may result in compensatory change in
endocrine regulation and be associated with
alterations in hormone catabolism
• In some instances, compensatory changes in

regulation and alterations in hormone
catabolism do not fully offset age-related
impairment in endocrine function
57
P RO B L E M S I N D I AG N O S I N G E N D O C R I N E
D I S O R D E RS
• Often present with nonspecific, muted, or atypical symptoms and

signs in older adults
• Complete absence of complaints is common
• Lab evaluation may be complicated by coexisting illnesses and

medications
• For most lab tests, normal ranges for healthy older people are not
available

58
I N T RO D U C T I O N TO
T H Y RO I D D I S O R D E RS
• With normal aging:

➢ Thyroxine (T4) levels remain unchanged
➢ Triiodothyronine (T3) levels are unchanged until extreme
old age, when they decrease slightly
➢ Distribution of TSH levels shifts upward → higher
prevalence of biochemical hypothyroidism in older adults
• TSH testing recommended:

➢ For all older adults with a recent decline in clinical,
cognitive, or functional status
➢ For patients admitted to a nursing home

59
D I S O R D E R S O F PA R AT H Y R O I D A N D C A L C I U M
M E TA B O L I S M
• Circulating levels of parathyroid hormone (PTH)

increase 30% between ages 30 and 80
• Despite changes in several systems that

regulate calcium homeostasis, serum calcium
levels remain normal due to increased PTH
• The balance between bone resorption and

bone formation is altered in favor of resorption

60
H O R M O N A L R E G U L AT I O N O F WAT E R
A N D E L E C T R O LY T E B A L A N C E
Older adults are predisposed to volume depletion

and free water excess, due to alterations in:
• Total body water content
• Secretion of antidiuretic hormone
• Osmoreceptor and baroreceptor systems
• Urine-concentrating capability
• Renal hormone responsiveness
• Thirst sensation

61
I N T R O D U C T I O N TO D I S O R D E R S
OF THE ADRENAL CORTEX
• With aging:
➢  Cortisol secretion is balanced by  clearance
➢ ACTH stimulation of cortisol production is unchanged
➢ Cortisol and ACTH responses are unimpaired
➢ Acute cortisol responses may be higher, more prolonged
• Unless emergent, adrenal function testing should be deferred until ≥48 hours
after major stressors such as trauma, surgery
• Endocrinology consultation if ACTH stimulation test is normal but adrenal

insufficiency is suspected

62
DHEA SUPPLEMENTATION
• Circulating DHEA levels:

➢ Decline with aging
➢ Are associated with poor health
➢ Are positively correlated with some measures of longevity and functional status
• Efficacy and safety of DHEA supplementation have not been established
• Use of DHEA is inappropriate outside clinical trials

ฮอร์ โมนและระบบต่ อมไร้ ท่อ
Affected Organ or Physiologic Change Clinical Manifestations
System
Endocrine system Menopause, ↓ estrogen and ↑ Incidence of diabetes
progesterone secretion ↓ Muscle mass
↓ Testosterone secretion ↓Bone mass
↓ Growth hormone secretion ↑ Fracture risk
↓ Vitamin D absorption and Vaginal dryness,
activation dyspareunia
↑ Incidence of thyroid Changes in skin
abnormalities Tendency toward water
↑ Insulin resistance and intoxication
glucose intolerance
↑ Bone mineral loss
↑ Secretion of ADH in
response to osmolar stimuli
PHYSIOLOGIC CHANGES OF AGING (1 of 5)
Body system Change Consequences
Nervous ↓ Number of neurons ↓ Muscle innervation
↓ Action potential speed ↓ Fine motor control
↓ Axon/dendrite branches
Muscle Fibers shrink Tissue atrophies
↓ Type II (fast twitch) fibers ↓ Tone and
↑ Lipofuscin and fat contractility
deposits ↓ Strength
Skin ↓ Thickness Loss of elasticity
↑ Collagen cross-links
Skeletal ↓ Bone density Movement slows and
Joints become stiffer, less may become
flexible limited
Heart ↑ Left ventricular wall
thickness
↑ Lipofuscin and fat Stressed heart is less
deposits able to respond
Vasculature ↑ Stiffness
↓ Responsiveness to
receptor-mediated
agents
Pulmonary ↓ Elastin fibers ↓ Effort-dependent
↑ Collagen cross-links and independent
↓ Elastic recoil of the lung ventilation (quiet
↑ Residual volume and forced
↓ Vital capacity, forced breathing)
expiratory volume, and ↓ Exercise tolerance
forced vital capacity and pulmonary
reserve
Eyes ↑ Lipid infiltrates/deposits ↓ Transparency of the cornea
↑ Thickening of the lens Difficulty in focusing on near
↓ Pupil diameter objects
↓ Accommodation and dark
adaptation
Ears ↑ Thickening of tympanic ↑ Conductive deafness (low-
membrane frequency range)
↓ Elasticity and efficiency of ↑ Sensorineural hearing loss
ossicular articulation (high-frequency sounds)
↑ Organ atrophy ↓ Detection of gravity, changes
↓ Cochlear neurons in speed, and rotation
↓ Number of neurons in the utricle,
saccule, and ampullae
↓ Size and number of otoliths
Digestive ↑ Dysphagia ↓ Iron absorption
↑ Achlorhydria ↓ B12 and calcium
Altered intestinal absorption absorption
↑ Lipofuscin and fat deposition ↑ Incidence of diverticula,
in pancreas transit time, and
↑ Mucosal cell atrophy constipation
Urinary ↓ Kidney size, weight, and ↓ Ability to resorb glucose
number of functional ↓ Concentrating ability of
glomeruli kidney
↓ Number and length of ↓ Renal clearance of
functional renal tubules drugs, toxins
↓ Glomerular filtration rate
↓ Renal blood flow

Immune ↓ Primary and secondary ↓ Immune functioning
response ↓ Response to new
↑ Autoimmune antibodies pathogens
increase ↓ T lymphocytes, NK cells,
↓ T-cell function; fewer naive cytokines needed for
and more memory T cells growth and maturation
Atrophy of thymus of B cells
Endocrine ↑ Atrophy of certain glands Changes in target organ
↓ Growth hormone, DHEA, response, organ system
testosterone, estrogen homeostasis, response to
↑ Parathyroid hormone, ANP, stress, functional capacity
norepinephrine, baseline
cortisol, erythropoietin

Normal age-related changes of the teeth,
gums, and salivary glands
72
AGE-RELATED CHANGES
IN ORAL TISSUES
Tissue Nature of change Clinical significance

affected
Tooth dentin Increased thickness • Diminished pulp space
Diminished permeability • Diminished sensitivity of dentin

resulting from sclerosis of • Diminished susceptibility to effects of
dentinal tubules bacterial metabolites
• Increased tooth brittleness
Dental pulp Diminished volume • Diminished reparative capacity
• Diminished sensitivity and change in
nature of sensitivity
Shift in proportion of • Diminished reparative capacity
nervous, vascular, and • Diminished sensitivity and change in
connective tissues nature of sensitivity
Salivary Fatty replacement of acini • Possibly less physiologic reserve
glands

Common Medical Considerations in
Dental Treatment of Older Adults
74
RELATIONSHIP BETWEEN ORAL HEALTH AND GENERAL

HEALTH
• Periodontal disease and the pathogens responsible for it have been linked
epidemiologically and immunologically with coronary artery disease,
peripheral vascular disease, cerebrovascular disease, and pneumonia.
• Several studies have demonstrated significantly reduced incidence of
institution-acquired pneumonia, reduced mortality, and reduced length of
hospital stay in patients on ventilators (SOE=B) and those in nursing homes
(SOE=C) when a program of daily oral hygiene is instituted. Daily oral
hygiene would improve oral health and could reduce pneumonia.

75
PERIDONTAL DISEASE AND DIABETES
• Periodontitis worse in patients with poorly controlled diabetes mellitus.

periodontitis, as a cause of chronic inflammation, impedes effective control of
diabetes.
• Periodontal disease can negatively impact glycemic control because
inflammation and infection can increase blood glucose.
• Poorly controlled diabetics can have more severe periodontal disease
because hyperglycemia can decrease the body’s ability to kill bacteria.
• Hyperglycemia can lead to increased glucose in the crevicular fluid around
the teeth which feeds the bacteria.

76
PERIODONTAL DISEASE AND CARDIOVASCULAR DISEASE
• Two potential mechanisms explain the association between periodontal

disease and cardiovascular disease.
• There can be direct infection from oral bacteria which causes an
inflammatory response and leads to plaque formation in the blood vessel.
• In addition, some periodontal pathogens can cause platelet aggregation
which can result in clot formation.

77
COMMON MEDICAL CONSIDERATIONS
IN DENTAL TREATMENT
• ⅓ of reported cases of infective endocarditis caused by

organisms normally found only in the mouth
➢ Persons at elevated risk for endocarditis should be counseled to
optimize daily oral hygiene, in order to limit gingival inflammation and
bacterial access to bloodstream
➢ Prophylactic antibiotic coverage recommended only in specific high-
risk situations. Routine antibiotic prophylaxis prior to dental treatment
is not indicated for individuals with prosthetic joint replacements.
• Anticoagulants normally do not need to be discontinued prior

to routine dental care, including most extractions. For
invasive dental treatment in a patient on an anticoagulant
regimen, as long as the INR is ≤ 3.5, the risks of
uncontrolled oral hemorrhage is minimal and outweighed by
the protective effects of anticoagulation.

78
OSTEONECROSIS OF THE JAW (ONJ)
• There are case reports of ONJ in patients treated with

bisphosphonates (BP) for bony metastases
➢ Women more likely affected than men, mandible more likely
affected than maxilla
• BP therapy for osteoporosis is unlikely to result in ONJ

• Patients who need a BP for bony malignant disease
should complete dental care before BP is started
• If dental surgery is undertaken in a patient with a history
of high-dose BP therapy, advise patient of increased risk
of osteonecrosis-related complications

79
ORAL HYGIENE IN
LONG TERM CARE FACILITIES
• The main goal in providing daily oral care is disrupting the plaque that
accumulates on the teeth and checking for any problems.
• Brushing and flossing are ideal, but may not be practical since flossing is
difficult to accomplish on another individual.
• Proxabrushes and other interdental brushes are often easier to use than floss
and may be better tolerated by the individual. Power toothbrushes with a
standard toothbrush head is often a best option for care providers since the
brush does the work.

80
ORAL HYGIENE IN
LONG TERM CARE FACILITIES
• For individuals with dementia, being in front for oral hygiene allows them to
see what is happening and may be beneficial.
• Use a toothbrush with a fluoride containing toothpaste to brush all of the
surfaces of all of the existing teeth.
• Spit out after brushing and you are finished.
• It is not necessary to rinse and can be beneficial by leaving more of the
fluoride in contact with the teeth.
• Dentures should be removed prior to cleaning the mouth.

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Introduction:

Biology and Clinical

• The major theories of how aging occurs

• The effects of aging on major organ systems

• How changes that occur with aging contribute to a systems-

Copyright © 2018 American Geriatrics Society

Functional capacity + Aging Process = Biological Age

These progressive changes have a biologic basis in

Copyright © 2018 American Geriatrics Society

• Homeostenosis = The narrowing of reserve capacity that

Copyright © 2018 American Geriatrics Society

Copyright © 2018 American Geriatrics Society

Body composition ↓ Lean body mass Changes in drug

• In youth, epidermis interdigitates with dermis

• With aging, the interdigitations flatten, resulting in:

Copyright © 2018 American Geriatrics Society

Aging is associated with decreased lipids in the top

• Dryness and roughness

Copyright © 2018 American Geriatrics Society

• Slower turnover of epidermal cells may account for

• Lower number of immune antigen-presenting cells

Copyright © 2018 American Geriatrics Society

• Decreases in collagen and elastin cause haphazard,

Copyright © 2018 American Geriatrics Society

• Shortened duration of anagen (growth phase of hair

Copyright © 2018 American Geriatrics Society

Eyes ↓ Lens flexibility Presbyopia

Ears Loss of high-frequency hearing ↓ Ability to recognize speech

Nose ↓ Smell ↓ Taste and

Peripheral nervous system ↓ Baroreflex responses Tendency toward syncope

Age effect Clinical implication

↓ Myocardial relaxation & ↑ Risk of diastolic heart failure and

Copyright © 2018 American Geriatrics Society

Age effect Clinical implication

Copyright © 2018 American Geriatrics Society

CLINICAL EFFECTS OF CV CHANGES

• In healthy older adults, age-related changes

• Reduced airway size

• Shallow alveolar sacs

• Reduced chest wall compliance

• Intercostal muscle atrophy

• Reduction in diaphragmatic strength by 25%

Copyright © 2018 American Geriatrics Society

Pao2 = 109 - (0.43 X age)

• A common misperception is that older people tend to

• Older people often have more than one cause of their

Copyright © 2018 American Geriatrics Society

•↓Number and volume of the •Delayed gastric emptying

↓ Myenteric plexus neurons and a Reduced colonic propulsive motility

Decreased liver mass, and perfusion Decrease Cytochrome P450 content

Age-related decreased synthesis of Lower amounts of vitamin K

• Impaired in many endocrine systems with aging

• Loss of function in one aspect of endocrine

• In some instances, compensatory changes in

• Often present with nonspecific, muted, or atypical symptoms and

• Complete absence of complaints is common

• Lab evaluation may be complicated by coexisting illnesses and

Copyright © 2018 American Geriatrics Society

• With normal aging:

• TSH testing recommended:

Copyright © 2018 American Geriatrics Society

• Circulating levels of parathyroid hormone (PTH)

• Despite changes in several systems that

• The balance between bone resorption and

Copyright © 2018 American Geriatrics Society

Older adults are predisposed to volume depletion