physiology of aging

1. Christine M. Khandelwal, DO
Jan Busby-Whitehead, MD
Ellen Roberts, PhD, MPH
The University of North Carolina at Chapel Hill
Physiology of Aging
©The University of North Carolina at Chapel Hill, Center for Aging and Health.
All Rights Reserved.
With Support from The Donald W. Reynolds Foundation

2. Learning Objectives
• Learners will be able to describe the normal
changes that occur with aging.
• Learners will be able to identify the common
age-related changes that occur in the
following systems: cardiovascular,
respiratory, renal, hematology/immune,
gastrointestinal, endocrine, neurologic,
musculoskeletal, and reproductive.
2

3. Aging
• Chronologic age is not an accurate predictor
of physical condition or behavior
• Poor health in later life is not inevitable
• The rate of physiologic decline can be
modified
• Much of the illness and disability associated
with aging is related to modifiable lifestyle
factors that are present in middle age:
» disparate factors predispose individuals to
functional losses later in life
» many conditions have suspected either
genetic and/or environmental etiologies
3

4. Aging and Disease
• It may not always be possible to differentiate
normal aging from disease
• Normal changes with aging reduce your
reserve capacity
• Aging results in a diminished ability to
maintain homeostasis and regulate body
systems
• Aging is accompanied by heterogeneity
4

5. Cardiovascular System
• The changes that normally occur in the
cardiovascular system with aging do not
significantly limit the normal work capacity of
the heart
• Advancing age increases the risk for
hypertension and coronary artery disease
5

6. Cardiovascular System
• The prevalence of coronary artery disease
at autopsy may reach 75 percent after the
sixth decade in men, two decades later in
women*
• The Baltimore Longitudinal study studied
highly screened older individuals and
found only a minimal impact of aging on
resting cardiovascular function such as
left ventricular ejection fraction**
6
*(Van de Veire NR, De Backer J. Ascoop AK, Middemacht B. Veighe A. Sutter JD. Echocardiographically estimated left
ventricular end-diastolic and right ventricular systolic pressure in normotensive healthy individuals. Int. J. Cardiovasc
Imaging. 2006;22(5):633).
**Fleg JL, O’Connnor F. Gerstenblith G. Becker LC, Clulow J. Schulman SP, Lakatta EG. Impact of age on the
cardiovascular response to dynamic upright exercise in health men and women. J Appl Physiol. 1995;78(3):890).

7. Cardiovascular System
• A study found that aging was accompanied
by an increase in LV mass and LA
dimensions and an increase in relaxation
abnormalities in normotensive individuals*
• Ageing was associated with increased mean
LV wall thickness, chamber diameter, mass,
concentric remodelling, and a decline in LV
diastolic function **
*(Van de Veire NR, De Backer J, Ascoop AK, Middernacht B, Velghe A, Sutter JD. Echocardiographically estimated
left ventricular end-diastolic and right ventricular systolic pressure in normotensive healthy individuals. Int J
Cardiovasc Imaging. 2006;22(5):633).
**(Gates PE, Tanaka H, Graves J, Seals DR. Left ventricular structure and diastolic function with human ageing.
Relation to habitual exercise and arterial stiffness. Eur Heart J. 2003;24(24):2213).
7

8. 8
Age-associated
Change
Common Clinical Consequence (s)
Valves calcium
deposits
Cardiac conduction problems
Pacemaker cell loss
(SA node)
Fibrous tissue/fat
deposits
Dysrhythmias
Baroreceptors Orthostatic hypotension
Arteries thicken/stiffen
Ventricular
cardiomyocytes
hypertrophy
Moderate increase in SBP
Not normally aging:
Atherosclerotic plaques or HTN

9. Respiratory System
• Most of the normal respiratory changes with
age are of little functional significance in
healthy older adults
• However, the normal anatomical changes do
reduce reserve capacity and increase
vulnerability to respiratory disease
9

10. Respiratory System
• Aging chest wall changes include increased
stiffness of the chest wall predominates over
an increase in compliance of the lung
parenchyma*
• A decrease in PaO2 and crease in alevolar-
arterial oxygen gradient is found in normal
aging lungs
• Carbon dioxide excretion is not impaired with
age and any changes in PaCO2 are due to
disease and should not be attributed to age
alone
*(Estenne M, Yernault JC, De Troyer A. Rib cage and diaphragm-abdomen compliance in humans: effects of
age and posture.J Appl Physiol. 1985;59(6):1842).
10

11. 11
Age-associated Change Clinical Consequence (s)
Vital capacity reduced
FEV reduced
Chest wall compliance
reduced
Alveolar PO2 does not change with age,
but age increases the alveolar-arterial (A-
a) oxygen gradient.
Reduced alveolar
elasticity and reduced
number of functional
alveoli
Decrease surface area for gas exchange
Reduced exercise capacity and reduced
reserve capacity
Cilia activity reduced
Glandular cells reduced
Lung macrophages less
effective
Cough less forceful
Increased risk of respiratory infections

12. Renal System
• Most changes do not cause clinically
significant disease or disability, but they do
leave the kidney vulnerable to illness or
medications that can depress renal function
and lead to acute or chronic renal failure.
• Normal aging is associated with diffuse
sclerosis of glomeruli such that 30 percent of
glomeruli are destroyed by age 75 *
*(Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney weight, and body surface in
normal man. Anat Rec. 1992;232(2):194).
12

13. 13
Age-associated Change Clinical Consequence (s)
Renal mass and size reduced
Average Creatinine clearance is
reduced 10ml/decade
Reduced the rate of blood flow
Decrease in excretion of
drugs/toxins
Renal tubular cells reduced,
thickened tubular walls
Decreased ability to concentrate
urine
Thirst is blunted
↓ serum renin and aldosterone
(30-50%)
Volume depletion
Dehydration
Increased prostaglandins
Reduction of urine acidification
and impairment in excreting
Prone to nephrotoxicity
Vulnerable to ischemic insult

14. Hematopoietic System
• Maintains adequate function with aging
• Overall, cell counts and parameters in the
peripheral blood are not significantly
different from in young adult life
» Red cell life span, iron turnover, and blood
volume are unchanged with age
• EPO response to anemia in older subjects is
similar to that of younger subjects*
*(Powers JS, Krantz SB, Collins JC, Meurer K, Failinger A, Buchholz T, Blank M, Spivak JL, Hochberg M, Baer A.
Erythropoietin response to anemia as a function of age. J Am Geriatr Soc. 1991;39(1):30.)
14

15. Hematopoietic System
• Functional reserves are reduced with age
due to a decreased bone marrow mass and
an increase in fat*
• Total circulating white cells counts do not
change with age in healthy older people, but
the function of several cell types is reduced
15
*(Kirkland JL, Tchkonia T, Pirtskhalava T, Han J, Karagiannides I. Adipogenesis and aging: does aging make fat go
MAD? Exp Gerontol. 2002;37(6):757).

16. Hematopoietic System
• The compensatory hematopoietic response
to phlebotomy, hypoxia, and other stressors
is delayed and less vigorous in the healthy
older person
• Observational studies have shown
increasing hypercoagulabailty state with
aging
» Higher risk of DVTs*
*(Franchini M. Hemostasis and aging. Crit Rev Oncol Hematol. 2006;60(2):144).
16

17. Immunologic System
• Immunosenescence - aging changes in
immune function:
» Diminished cell mediated immunity
» Increased incidence of anergy
» Reduced helper, cytotoxic and effector T cells
» Increased cytokine antagonists
» Changes in neutrophil and macrophage function
17

18. Immunologic System
• Immunosenescence contributes to increased
frequency of infections, malignancies, and
decreased changes of developing adequate
immunity*
*(Agarwal S, Busse P. Innate and adaptive immunosenescence. J Ann Allergy Asthma Immunol. 2010;104(3):183).
18

19. Gastrointestinal System
19
• The physiologic changes of an aging GI
system are minor
• Aging itself does not cause malnourishment
• Normal aging changes:
» The amplitude of esophageal contractions
during peristalsis decreases, but the
movement of food is not impaired
» the prevalence of H.Pylori increases with
advancing age
» Transaminases and alkaline phosphatase are
minimally affected by age

20. 20
Age-associated Change Clinical Consequence (s)
Gastric cells reduced
Increased post prandial
gastric pH
Gastritis
Less effective mastication
Decreased food clearance
Increased risk of aspiration
Muscle tone reduced,
peristalsis reduced
Constipation
Hepatic size reduced, blood
flow reduced
Less efficient in metabolizing
drugs/toxins

21. Endocrine System
• Because the endocrine system is so complex
& interrelated it is difficult to discern the
effects of aging on specific glands
• 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
21

22. 22
The Endocrine System
• Hormonal alterations are variable & gender-
dependent:
• Most apparent in:
» glucose homeostasis
» reproductive function
» calcium metabolism
• Subtle in:
» adrenal function
» thyroid function

23. Genitourinary System
• Aging changes in the genitourinary system
increase the older person's risk of:
» urinary incontinence
» urinary tract infection
» erectile dysfunction
» dyspareunia
• The prevalence of urinary incontinence
increases with age due to:
» decrease in detrusor muscle contractility
» decrease in maximum bladder capacity
» decrease ability to withhold voiding
» an increase in postvoid residual
23

24. 24
Men
‣ Testes become softer & smaller
‣ Prostate enlarges; fewer viable sperm are
produced & their motility decreases
‣ May not experience orgasms every time
they have sex
‣ Erections are less firm & often require
direct stimulation to retain rigidity
The Reproductive System

25. 25
Women
• The “climacteric” occurs (defined as the
period during which 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
• Atrophy of vaginal tissues, hot flashes,
sweats, irritability, depression, headaches,
myalgias, sexual desire is variable
The Reproductive System

26. 26
The Neurological System
• Increased:
» Abnormal
proteins
» Cerebral atrophy
» Changes in
sleep patterns
» Stroke risk
• Reduced:
» Neurons
» Neurotransmitter
levels
» Lipid turnover
rate

27. Neurologic System
• The weight of your brain peaks around age
20 and then a modest decline occurs with
age that is limited to the gray matter (outer
surface of the brain) in healthy older people
• Cardiovascular disease and hypertension are
predictors for cognitive impairment*
*(Newman AB, Arnold AM, Sachs MC, Ives DG, Cushman M, Strotmeyer ES, Ding J, Kritchevsky SB, Chaves PH,
Fried LP, Robbins J. . Long-term function in an older cohort--the cardiovascular health study all stars study. J Am
Geriatr Soc. 2009;57(3):432)
27

28. Sensory Changes
• As you age, your senses (vision, hearing,
taste, smell, touch) may become less acute
• The most dramatic sensory changes with age
affects vision and hearing
• Many of the changes can be compensated
for with assistive devices (e.g., glasses,
hearing aids, etc.) or by changes in lifestyle
28

29. 29
Neurologic System
• As people age, they usually experience such
memory changes as slowing in information
processing, but these changes are benign
• Short-term and remote memories aren't
usually affected by aging; recent memory
may be affected
• Not progressive and does not interfere with
daily function or independence

30. 30
Age-associated Change Clinical Consequence (s)
Middle ear membranes and
bones less flexible
Decreased hearing sensitivity
Pupil size reduced
Lens becomes rigid
Ability to produce tears
reduced
Decreased ability to focus at
near range, less tolerance to
glare
Dry eyes
Functional smell receptors
reduced
Diminished sense of smell
Taste buds reduced in size
and numbers
Diminished taste
Touch receptors reduced,
response to painful stimuli
reduced
Diminished sense of touch

31. The Musculoskeletal System
• Sarcopenia: age-related loss of muscle mass
and strength
» Loss of muscle is greater and faster from the
legs than from the arms
» Activity may decrease rate of decline
» The loss of muscle contributes to age-related
changes in body composition, and distribution
for water soluble drugs*
• Type 1 slow-twitch fibers are less affected by
age than fast-twitch fibers
» Older muscle easily fatigues
31
*(Degens H. Age-related skeletal muscle dysfunction: causes and mechanisms. Musculoskelet Neuronal Interact.
2007;7(3):246)

32. The Musculoskeletal System
• The primary factors contributing to reduction in height
include compression of vertebrae, changes in posture,
and increased curvature of the hips and knees
• The “wear-&-tear” theory regarding cartilage
destruction & activity doesn’t hold up as osteoarthritis
is also frequently seen in sedentary elders
• Decrease H20 in the cartilage of the intervertebral
discs results in a ↓ in compressibility and flexibility
• Decrease H20 content of tendons & ligaments
contributing to ↓ mobility
32

33. The Musculoskeletal System
• Gradual loss of bone mass (bone resorption
> bone formation) starting around age 30s
• Aging in both men and women increases the
probability of fracture and once a fracture
occurs, the rate of repair is slowed
• Vitamin D deficiency further accelerates bone
loss
• Increasing weight bearing time or loading
forces may result increase bone mineral and
prevent age-related bone loss*
*(Schwab P, Klein R. Nonpharmacological approaches to improve bone health and reduce osteoporosis. Curr Opin
Rheumatol. 2008;20(2):213).
33

34. 34
Hair, Nails, and Skin
• 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
» Thinning of the epidermis allows more fluid to
escape the skin
• Skin shears easy due to decrease in surface
area
• ↓ function of sebaceous & sweat glands
» dry skin
» reduced ability to cool the body
» wrinkles, sagging of skin

35. Hair, Nails, and Skin
• Mechanical protection altered
• Tendency to hypothermia
• Vulnerability to heat and cold
• Decreased barrier function
• Lax skin
35

36. 36
Treatment Implications
• Consider earlier and more aggressive
treatment of infections BUT with attention to
renal function
• Pay closer attention to nutrition and bowel
function
• Pay close attention to CNS changes as
harbingers of other pathologies
• Screen carefully for metabolic disorders:
thyroid, anemias, bone disease, vitamin
deficiencies

37. 37
• It is not always possible to differentiate
normal aging from disease
• Many of the normal changes of aging do not
cause clinically significant declines in function
• Changes in the cardiovascular, respiratory,
and gastrointestinal do not affect the ordinary
activities of a healthy older adult
Key Points:

38. 38
References
• Rughwani, N. (2008). Physiology of Aging. POGOe - Portal of
Geriatric Online Education. Retrieved February 21, 2011 from
http://www.pogoe.org/productid/20284
• GRS 7th edition – American Geriatrics Society
• Van de Veire NR, De Backer J, Ascoop AK, Middernacht B, Velghe
A, Sutter JD. Echocardiographically estimated left ventricular end-
diastolic and right ventricular systolic pressure in normotensive
healthy individualsInt J Cardiovasc Imaging. 2006;22(5):633)).
• Fleg JL, O'Connor F, Gerstenblith G, Becker LC, Clulow J,
Schulman SP, Lakatta EG. Impact of age on the cardiovascular
response to dynamic upright exercise in healthy men and women.J
Appl Physiol. 1995;78(3):890).
• Gates PE, Tanaka H, Graves J, Seals DR. Left ventricular structure
and diastolic function with human ageing. Relation to habitual
exercise and arterial stiffness. Eur Heart J. 2003;24(24):2213).
• Estenne M, Yernault JC, De Troyer A. Rib cage and diaphragm-
abdomen compliance in humans: effects of age and posture. J Appl
Physiol. 1985;59(6):1842).
• Glomerular number and size in relation to age, kidney weight, and
body surface in normal man. Anat Rec. 1992;232(2):194).

39. 39
References
• Powers JS, Krantz SB, Collins JC, Meurer K, Failinger A, Buchholz
T, Blank M, Spivak JL, Hochberg M, Baer A. Erythropoietin
response to anemia as a function of age.J Am Geriatr Soc.
1991;39(1):30.
• Kirkland JL, Tchkonia T, Pirtskhalava T, Han J, Karagiannides I.
Adipogenesis and aging: does aging make fat go MAD? Exp
Gerontol. 2002;37(6):757.
• Franchini M. Hemostasis and aging. Crit Rev Oncol Hematol.
2006;60(2):144.
• Degens H. Age-related skeletal muscle dysfunction: causes and
mechanisms. Musculoskelet Neuronal Interact. 2007;7(3):246.
• Agarwal S, Busse P. Innate and adaptive immunosenescence. JAnn
Allergy Asthma Immunol. 2010;104(3):183.
• Newman AB, Arnold AM, Sachs MC, Ives DG, Cushman M,
Strotmeyer ES, Ding J, Kritchevsky SB, Chaves PH, Fried LP,
Robbins J. . Long-term function in an older cohort--the
cardiovascular health study all stars study. J Am Geriatr Soc.
2009;57(3):432)
• Schwab P, Klein R. Nonpharmacological approaches to improve
bone health and reduce osteoporosis. Curr Opin Rheumatol.
2008;20(2):213.

40. Acknowledgements and
Disclaimer
This project was supported by funds from The Donald
W. Reynolds Foundation. This information or content
and conclusions are those of the author and should not
be construed as the official position or policy of, nor
should any endorsements be inferred by The Donald
W. Reynolds Foundation.
The UNC Center for Aging and Health, the UNC
Division of Geriatric Medicine and the Department of
Family Medicine also provided support for this activity.
This work was compiled and edited through the efforts
of Carol Julian.
40

41. 41
©The University of North Carolina at Chapel
Hill, Center for Aging and Health.
All Rights Reserved.