Physiology of older

individuals
Dr. Silvia Montaner
Oncology and Diagnostic Sciences
ODSC518P 2023 Fall
 Physiology of older
individuals
• Increase in the population between 65-85 years old and older than 85.

• Healthy older adults experience normal physiological changes associated with senescence and aging in most systems.

• Together, these changes lead to a diminished physiological reserve = Older persons can function sufficiently in a
rested or non-stressed state BUT the capacity to respond to stress is decreased.

• An older person responds differently to stress of acute illness, increased anxiety or increased physical demand.

• Elderly persons have the highest mortality in the adult surgical population.

• Conflictive literature regarding association of specific diseases with aging processes.

Physiological features of Aging Persons (JAMA Surgery / Arch Surgery) and other publications.
 Alterations in cardiac physiology
• Heart pumping:

• Progressive loss of myocytes → ↑ myocyte volume in both ventricles (ventricular hypertrophy).

• Cellular structural changes: collagen concentration and its crosslinking increases, loss of elasticity , infiltration with
amyloid → increased wall thickness and stiffness (25% thicker) and decreased contractility (particularly LV).
◦ Decrease in compliance, increase in afterload, and decrease in early diastolic filling.
◦ Atrium compensates with increased atrial contraction particularly during the latter phase of ventricular filling. This
leads to atrial hypertrophy and enlargement. Valves also thicken and becomes stiffer, sometimes calcified.
◦ Overall, decreased contractility, heart fills more slowly, so duration of myocardial contraction is increased.
◦ Atrial gallop and murmurs on auscultation.

• Ejection fractions tend to remain the same in women and decrease in men. Stroke volume may increase. Cardiac output
may decrease or increase.

• However, maximum cardiac output, ejection fraction, and aerobic capacity during exhaustive upright exercise or
increased work demand) are reduced with age.
 Alterations in cardiac physiology
• Heart rate:

• Number of pacemaker cells in the sinus node decreases. Development fibrous tissue and fat deposits as well.

• The duration of myocardial contractility is increased.

• →These changes may result in a slightly slower heart rate.

• The β-adrenergic responsiveness of the heart decreases, limiting the maximum achievable heart rate (HR).
• → Decline in responsiveness in terms of maximal heart rate.
• Smaller aerobic workload possible - reduction in the extent of cardiac exertion that can be
tolerated for a period of time.
• Slower aerobic performance.

• Even if resting HR does not change with age, the maximum achievable HR decreases, with the maximal HR that an 85-
year-old person can achieve being approximately 70% of that of a 20-year-old person.

Overall cardiac reserves diminish with age.

 Alterations in vascular
physiology
Structure of vessel layers:
• Intima layer: thickening.
• Media layer: collagen cross-linking and decrease in elastin content + decrease in NO production with age leads to
Dysfunctional SMC tone regulation
• → leads to increased stiffness and decreased vascular compliance.
• → affects tissue perfusion. In heart, insufficient coronary perfusion/oxygenation further affecting cardiac reserve

Blood pressure:
• Aging causes an increase in systolic pressure (systolic hypertension)
increased in pulse pressure (decrease in diastolic pressure after 60s, because of stiffness and lower
compliance).
• Increased in pulse pressure: sign of decreased vascular compliance
predictor of cardiovascular diseases, independent of systolic hypertension.
• Decreased diastolic pressure also compromising myocardial perfusion.
 Alterations in pulmonary
physiology
Changes:
• Chest wall stiffness increases because of cartilage calcification, arthritis, fibrosis, and gradual atrophy and weakening
of the intercostal muscles. Greater demand from the diaphragm and abdominal muscles for breathing, but their
strength also decreases with age.
• Changes in alveoli. Enlargement of alveolar spaces and increased thickness of alveolar basement membrane.
Decrease in cumulative surface area for gas exchange.
• Decreased chest wall compliance and decreased respiratory muscle strength.
• Decreased lung elastic recoil.
• Decreased vital capacity and forced expiratory volume (FEV). More air trapping.
• Decreased gas exchange capabilities and increased ventilation-perfusion mismatch.
• Overall, there are decreased in lung capacity and respiratory reserve. Diminished ventilatory response to
hypercapnia and hypoxia.
• Decreased mucocilliary clearance, decreased cilia, and decreased immune responses lead to increased susceptibility
to infections.
 Alterations in hepatobiliary physiology
• Changes:
• Liver size decreases after the age of 50 years (20-40% volume loss) because of decreased total number of
hepatocytes. Many hepatocytes undergo senescence and then apoptosis. Liver compensates with hepatocyte
hypertrophy.
• Morphological changes in sinusoids, blood flow decreases, and exchange of molecules decreases.
• Delay in liver regeneration.

• Functionality:
• Hepatic enzymatic rates may be decreased. Decreased capability for blood filtration, detoxification, ethanol
elimination, and protein conjugation. Drug metabolism is decreased (cytochrome P450 activity decreased).
• → increased susceptibility to damage by drugs, alcohol and toxins.
• Rate of plasma protein synthesis (including albumin, clotting factors, etc) may be reduced.
• → reductions in albumin and bilirubin levels. If challenged, protein synthesis is unable to increase significantly
beyond baseline.
• Lipid metabolism and sensitivity to insulin are decreased.
• → lipid accumulation and insulin resistance.
Overall – decreased functional reserve if challenged.
 Alterations in gastrointestinal
physiology
Changes in neuromuscular function:

Upper GI tract (oropharynx and esophagus) :

• Neuromuscular degeneration and muscle weakness → aberrant contraction

• Decreased coordination of reflexes for successful swallowing and food propulsion.

• → Muscles of upper esophageal sphincter (particularly cricopharyngeus muscle) show susceptibility to motility
changes.
• → Neuromuscular deficits of the lower esophagus lead to general weakness and slowing of contractions →
insufficient resting pressure in the lower esophageal sphincter → gastroesophageal reflux.

* These changes are related to GI disorders such as hiatal hernia, achalasia, diffuse esophageal spasm, reflux,
aspiration, dysphagia, and pharyngoesophageal diverticula.

No conclusive data on changes in gastric emptying times. No changes in transit in small intestine.
 Alterations in gastrointestinal
physiology
Changes in GI wall structure (changes in absorption and motility):

Small intestine:

• Progressive decrease in the height of the villi, with decreased surface area available. Also, fibrous connective tissue
start replacing mucosal parenchyma and smooth muscle cells →decreased absorption capacity (calcium).

Colon:

• Thickening of the muscular layers due to elastogenesis and a buildup of elastin between myocytes in the intestine
wall. Total collagen content and distribution is also increased. Area most affected is the taeniae coli.
• → These morphological changes (elastosis) lead shortening of the taeniae coli and a subsequent changes in the
circular muscle layer. This affects contraction capabilities and contributes to hard stools and constipation.
• → If inflammation and atherogenesis occur, hypertrophy and hyperplasia of muscle cells occur, worsening the
condition.
• → Association with most common age-related colonic disease, diverticular disease.
• → Associated with colorectal cancer development.
Stomach: gastric mucosa may become atrophic.
• → Association with disease processes, including atrophic gastritis.
 Alterations in gastrointestinal
physiology
Changes in Secretion and Absorption

• Salivary glands: Aging may affect flow rate and composition of saliva (ion composition, higher levels of mucin).

• Stomach: Conflictive results regarding secretion of gastric acid and pepsin. Decrease seems to correlate with
those patients in whom age-related mucosal atrophy is present.

• Pancreas: pancreatic lipase may be decreased, possibly accounting for impairment of fat absorption observed in
elderly persons.

• Gallbladder: Increase in incidence of cholelithiasis (↑in ratio of lipid-cholesterol in bile), but the underlying
process for it has not been elucidated.
 Alterations in endocrine,
immune and stress responses
Reproduction-related endocrine changes:
Females: Menopause
• Hormone levels changes: estrogen and progesterone  and FSH (and LH) .
• Bone loss from a loss of estrogen-mediated calcium homeostasis. Osteoporosis and pathological bone fractures.
• Absence of estrogen's cardiovascular protective effect, increasing LDL , decreasing HDL and increasing atherogenesis.
• Other changes in vasomotor symptoms, urogenital atrophy, increased mood swings, and loss of libido. *Hormone
therapy alleviates symptoms, although well-known risks have been documented, including increased risks of venous
thrombosis, stroke, and breast cancer.
Males:
• Sex hormones slowly decline with advancing age, while sex hormone–binding globulin increase. The decrease in sex
hormone–binding globulin further decreases the level of free active testosterone.
• Low testosterone levels are associated with decreased libido, decreased hematocrit, muscle atrophy, osteoporosis,
and possibly erectile dysfunction. *Testosterone replacement has shown to improve symptoms in men with clear signs
of hypogonadism.
 Alterations in endocrine,
immune and stress responses
Thyroid gland :

• Gland shows mild atrophy, fibrosis, and decreased size of the follicles. Less thyroid hormone and decreased iodine
uptake may occur.

• Subclinical hypothyroidism, normal free thyroxine (FT4) and increased thyrotropin (TSH) (3 - 16 % in 60 years old and
older). Not associated with impairment of physical and cognitive function, depression, or metabolic disturbances.
Hormone replacement treatment (levothyroxine therapy) is used but it is controversial. No clinical benefits.

Parathyroid glands:

• Increase in serum PTH hormone level compared with younger individuals, caused by decline in renal function and
dysregulation of calcium, phosphate and vitamin D homeostasis. Implicated in osteoporosis and bone loss. Calcitonin
levels seem to decrease with age.

Adrenal function:

• Changes in the diurnal pattern of cortisol, which shifts earlier in the day and produces higher evening cortisol levels. This
may lead to sleep disturbances (relatively earlier bedtime and awakening compared with younger individuals).

• Increase in epinephrine and norepinephrine; HOWEVER, the response of stimulation is reduced. The attenuated
sympathetic response of body stress manifests in several ways: less cutaneous vasoconstriction to cold stimuli, (more
susceptibility to hypothermia), decreased capacity to efficiently regulate pulse rate, blood pressure, blood pH.
 Alterations in endocrine,
immune and stress responses
Anterior Pituitary:

• Decrease in growth hormone and GH actions. Associated with decreased lean bone mass and skeletal musculature and
increased percentage of body fat.

• *GH therapy as anti-aging therapy is very controversial because of serious side effects: joint pain, edema, carpal tunnel
syndrome, increase in muscle mass but not increased strength, diabetes and cancer.

• Endocrine pancreas:

• Progressive increased insulin resistance, independent of obesity and sex (age 80s). OGTT test (45% rate of impaired
tolerance). Due to to neurohormonal changes, decreased capacity of uptake glucose, and others. Overall, there is an
age-related increase blood glucose levels, both in in fasting and fed stages.
Immune function:
• Decreased cellularity of pluripotent cells in bone marrow.
• Functional impairment of T-lymphocyte–mediated immunity
• Decreased stress-related increase in natural killer cell activity.
→ Overall increased susceptibility to infections.
 Alterations in renal physiology
• Renal weight and volume decrease due to cortical tissue loss. There is loss of parenchyma,
decreased number of nephrons, and glomerulosclerosis (obliteration of glomerular capillary
architecture), leading to decrease in renal blood flow and thus filtration.

• Tubular senescence leads to decreased tubular length, leading to decreased reabsorption and
secretion of solutes.

• Decreased renin production by juxtaglomerular apparatus, decreasing the the function of the
renin/angiotensin/aldosterone, leading to increased susceptibility to blood volume, electrolyte
and acid-base abnormalities.

• Attenuated antidiuretic hormone response.

• GFR decreases and filtration reserve decreases.
• Decreased sodium reabsorption and decreased potassium and hydrogen excretion.
• Loss in urine concentrating ability.

• Overall, there is fluid, electrolyte, and acid-base dysregulation and reduced renal reserve.

• Because of the diminished GFR, drugs that are cleared via the kidneys require dose
modification.
 Theories on Human Aging (not
for exam)

A) Programmed Theories
◦ Programmed longevity
◦ Endocrine Theory
◦ Immunological Theory

B) Damage/Error Theories
◦ Rate of Living Theory
◦ Free Radicals Theory
◦ Wear and Tear Theory
◦ Somatic DNA Damage
◦ Cross linking Theory
 Theories on Human Aging
A) Programmed Mechanisms
Existence of an intrinsic, genetically- programmed biological clock.
• Programmed longevity theory = different components
◦ Telomerase shortening/telomerase activity.
◦ Limited amount of cell divisions. Hayflick limit: number of times a cell population divides before
entering senescence.
◦ Specific genes related to prevention or promotion of cell aging and cell senescence.
• Antagonistic pleiotropy theory: arises when alleles that have beneficial effects on certain life
conditions and deleterious effects in other life conditions .
• Endocrine theory = existence of hormonal networks GH/Insulin/IGF1 that act as biological clocks to
control the pace of aging.
• Immunological theory = a dysfunctional and weaker immune system leads to increased
vulnerability to infectious disease and age-related physiological decline.
 Theories on Human Aging
B) Damage/Error Mechanisms

Progressive accumulations of molecular and cellular defects.

• Caloric restriction theory = prolonged calorie restriction extend both the median and maximal lifespan. Possibly
involves significant alterations in energy metabolism, oxidative damage, insulin sensitivity, inflammation, and
changes in both the neuroendocrine and sympathetic nervous systems.
• Free radical theory = aerobic metabolism causes cumulative ROS oxidative stress (which antioxidant mechanisms
no longer compensate). This leads to mitochondrial DNA damage and mitochondrial dysfunction .
• Somatic DNA damage theory = rate of DNA damage accumulates along with p53 mutations.
• Cross-linking theory = detrimental cross linking reactions including glycation.
• Waste accumulation theory = damaged components accumulate because of decreased autophagy. This changes
the cellular structural organization. Cellular components are displaced, and cellular functions are impeded.
• Wear and Tear theory = essential cellular and tissue components wear out with time.
• Disposable soma theory = organisms age as an evolutionary advantage to assure DNA repair and somatic
maintenance, for successful reproduction for species survival. Organisms must devote limited resources either
to produce more offspring or to live longer. Evolutionarily, the first is the most beneficial.
 Considerations
• Studies done in animals not humans.
• Specific cohorts.
• Mathematical models, no consideration of organ pathologies, disorders, etc.
• Anti-aging treatments, cocktails, etc
The end