BIOL 355 – Biology of Human Aging
Gerontology: study of the aging process, from maturity to death. Consists of biological
aging, psychological aging, and social aging (also environmental, economic, cultural and
Gerontologist: uses multidisciplinary concepts to study all aspects of aging process
Geriatrics: branch of specialized medicine
Geriatrician: concerned with health, care, diseases, and treatment of older adults.
Biogerontology: field that studies the biological aspects of aging (physical changes in
tissues, organs and systems that lead to changes in appearance and functional capacity).
Chronological aging: passage of time from birth for that individual; good for population
o Poor indicator of biological age because it is based on time only, arbitrary,
relative and subjective.
o Young-old: 60-74
o Old-old: 75-84
o Oldest-old: 85+
Biological aging: based on functional capacity; good for individuals.
o Functional capacity is measure of the ability of our cells, tissues, and organ
system to function optimally.
o Diverse because of varied onset of aging, rate which it progresses, and extent to
which it progresses.
o Influenced greatly by extrinsic factors, lesser by intrinsic factors (more
environment than genetics).
o Extrinsic factors (control over): lifestyles/nutrition, environment, medical
o Intrinsic factors (no control over): genetics
o Defined by 4 different criteria
Decline of functional properties
Loss of homeostasis
Decreases ability to adapt to stimuli
Increased vulnerability to disease and mortality
Normal biological aging: structural elements within the body deteriorate. Leads to loss
of functional capacity and decreased ability to adapt to internal and external stressors.
The reduced capacity to respond to changing internal and external environments; loss of
homeostasis. Loss of homeostasis leads to an increased likelihood of disease and death. o Loss of functional capacity in cells, tissues, and organs: brain and liver weight
decreases, BMR decreases, cardiac output decreases, respiratory capacity
decreases. A lifetime of stress, wear and tear and degradation of cells without
being replaced affects organ functions.
o Loss of homeostasis: when relative constancy is disturbed (compensation for
stressor fails), our cells are not operating in an optimal environment and cannot
function to their maximum potential.
o Biological aging causes change to structures and to negative feedback that allow
more rapid or extreme alteration in body conditions; leads to decrease detection
o Decreased ability to handle stressors: response to stress depends on many
factors (age, health, type, persistence). Adequate responses to stress include
mobilizing energy, activating defense mechanisms, repairing damage.
Frailty: state of vulnerability to poor resolution of homeostasis after a stressor event;
consequence of cumulative decline in many systems
Longevity: duration of life.
o Maturation (birth-18yrs): growth and development, acquire new functions,
perfect acquired functions, changes are beneficial
o Maturity (18-30yrs): period of stabilization
o Senescence (30yrs and beyond): no growth or development, changes are
Aging Demographics and Trends
o More people are now 65+ than under 25
o Populations in which 10% is aged 65+ is considered old; Canada is at 15%
o Fastest growing segment is 85+
o A steady increase in number of centenarians; aged 100+
Four reasons for increased elderly population:
o Baby Boomers are now 65+
o Decrease in infant mortality
o Increase in life expectancy (due to medical advances, public health)
o Decrease in birth rates (less young people)
Life span: the age at death the longest lived individual of a species; fixed for each
Life expectancy: the average age at which death occurs for members of the population;
varied; can be from birth or any age (ex birth – LE is 85 years; at age 50 – LE is 30 years)
o Historical period which you were born and lived: In Ancient Rome LE was 22
o Country in which you live: Some third world countries have a lower LE of about
o Gender: Women consistently outlive men by 5-7 years Age-independent mortality: deaths by chance; occur at any time; not related to a
o Acute illness, accidents, overdoses, murder, suicide, war, disaster
Age-dependent mortality: increased risk of dying with increased age; progressive,
natural impairments to cellular function and tissues which causes an increase in age-
specific death rate; death due to biological processes
o Chronic disease in the elderly, natural deaths
Premature deaths: large, devastating challenges the body cannot overcome, even with
proper organ function
o Accidents, overwhelming infection, cancer
If you cured all disease, years of life could be added. If you could slow the natural aging
process, you can reach maximum life span.
Demographics of population: statistical study of human populations including size,
density, geography of population; vital statistics on birth, death, disease, marriages.
o Cohorts of people (~100 000) are followed from birth to death
o Type 3 Survivorship Curve: can see a rectangularization from more people living
longer. Increase in life expectancy is due to reductions in infant, maternal and
early childhood mortality; medical advances, nutrition, technology, sanitation,
socioeconomic and environmental factors. Gains are less in increasing total years
lived because we do not have as much success eradicating chronic diseases.
o Non-Aging Survivor Curve: for primitive populations; same risk of death every
year (50%); animals do not live long enough in the wild to show signs of aging
due to predation, disease, habitat, starvation, accidental death. Ancient Romans
would be considered a non-aging population, as their life expectancy was only
o The “Ideal” Type 3 Survivorship Curve: where people die from natural causes;
accident free, disease free, and violence free. Even in an ideal survivorship, we
will see a brief downward turn for infant mortality. We still have stillborn babies,
genetic abnormalities and malfunctioning that we can’t eradicate in utero, we
will still have a small amount of infant mortality. After that, we have a huge flat
line indicating a complete lifespan of 75-100 where majority of the deaths are a
downward turn around 85. We have a small amount of survivors into 100-110
and that’s why we get that flat tail at the end. It would be as significant as the
infant mortality – not a lot. Most people would live a full life.
o We are a population that has switched from deaths from acute infectious
diseases to chronic diseases.
Aging – “CUPID” – Cumulative, Universal, Progressive, Intrinsic, Deleterious
Disease – “TSDIEOD” – Treatable, Selective, Discontinuous, Intrinsic/Extrinsic,
Aging is not a disease. Morbidity: increased incidence of disease with increased age. The condition where an
individual is so mentally or physically disabled by chronic diseases that they become
immobile or dependent on care of others.
Comorbidity: death due to multiple diseases
o Leading cause of premature death
o Rapid onset
o Fast deterioration in health
o Short term (<6 weeks)
o Infectious disease
o Most resemble normal aging
o Long term (>6 weeks)
o Persistent and get worse with time
o Not curable
o Not contagious
o Gradual deterioration of health
o Progressive, occur in incremental steps
o Clinical Threshold: disease may develop for many years before symptoms are
o Progressive loss in organ function
Progression of Chronic Disease:
o Cellular changes: undetectable minor changes to cells
o Tissue changes: microscopically visible damage
o Asymptomatic: detected by lab test
o *Reached Clinical Threshold*
o Disease symptom: progression to disability
o Disability or death
Exponential increased risk of chronic disease as age increases; accidents are relatively
stable then increase because it is not necessarily age-dependent.
Greatest drops in cardiovascular disease due to public health and awareness.
Rates of diseases that do not necessarily cause mortality (hypertension, arthritis,
chronic bronchitis, liver disease, kidney disorders, etc.) give an idea of health of the
older population by looking at comorbidity.
Top 5 Causes of Death Ages 15-34:
o Homicide (male)/cancer (women) o Suicide
o Cancer (male)/homicide (female)
o Heart disease
Top 5 Causes of Death Ages 55-74:
o Heart disease
o Accidents (male)/diabetes (female)
o COPD (male)/accidents (females)
Cannot “cure” chronic disease; we can analyze risk factors in order to devise a strategy
to slow the rate of progression and therefore postpone the disease.
Chemical level cellular level tissue level organ system level organism level
Since aging is universal (CUPID) and all humans have 4 macromolecules in common, it is
thought that changes in these macromolecules could cause aging
The Cell: the basic unit of life that contains enzymes and chemicals for anabolism
(building material) and catabolism (burning energy). Cells have different roles and the
roles are specified by different proteins and genetic information found in the nucleus.
o Plasma membrane: fluid mosaic model; phospholipid bilayer with many
embedded proteins that carry out specific functions. It is selectively permeable.
o Proteins for transport (ionic channels that will allow things to pass through)
o Cell-cell recognition (depicts majority of carbohydrates and sugars,
predominantly on outside of plasma membrane or outside of organelle
membrane) – reach out, test environment, communicate from cell to cell.
o Communication between proteins – Receptors and ligands. Ligands can bind
carbohydrates, hormones, etc.
o Enzymes: majority of proteins will be enzymes. If they bind to ligand they will
initiate a reaction.
o Tagging: cell-identification, for a cell to go to a specific tissue. These proteins will
have unique tags to go to a designated area.
o Tissue/Cell Specificity: propriety, detection from immune system
o Glycoproteins: used for specificity markers; signal what type of cell they are on
and who they belong to (identity)
Cytoplasm: contains organelles, proteins, and inclusions (glycogen, fats, pigments).
Organelles: small organs in the cell o Endoplasmic reticulum: folded membrane system that is continuous with
nucleus. Rough ER has ribosomes attached for protein synthesis. Smooth ER is
for lipid and steroid synthesis and carbohydrate and toxin metabolism.
o Ribosomes: attached to RER or free; composed of rRNA and protein; synthesize
o Mitochondria: “powerplant”; burns fuels to make energy
o Lysosomes: “garbage can”; contains digestive enzymes to break down old cells
and foreign particles and recycle macromolecules and organelles
o Golgi apparatus: “traffic director”; final processing of new proteins by attaching
glycolipid markers to tell them where to go and are packaged into vesicles
o Nucleus: nuclear membrane surrounds genetic material (DNA or chromosomes)
o Chromosomes: fibres of DNA, contains genetic information for protein synthesis
and therefore cell function on genes.
o 20 different amino acids can be arranged in infinite sequences
o Conformation (unique structure of bends, folds and twists) is key to specificity
and function of cell
o Primary: linear sequence of amino acids (polypeptide chain)
o Secondary: alpha helix or beta sheet of two polypeptide chains
o Tertiary: multiple helices and sheets folded together
o Quarternary: globular protein
o Structural proteins: usually linear and insoluble, stable. Provide mechanical
strength to tissues (collagen, keratin, elastin)
o Functional proteins: globular, water soluble, active and play major roles in
biological processes. Enzymes (biological catalysts) and haemoglobin (functional
o DNA protein: the order of nucleotides in the gene dictates the amino acid
sequence of the primary protein.
Transcription: occurs in nucleus; order of bases in DNA determines order
of amino acids in mRNA
Translation: occurs in cytoplasm; mRNA takes information to ribosomes
where proteins and synthesized. The specific amino acid sequence codes
for a specific protein.
Theories of Aging
Types of Cells in Body:
o Continuously mitotic: divide and produce new cells throughout lifespan; rate
does decrease with age. Bone marrow, epithelium, skin, fibroblast cells. o Post mitotic: divide during embryogenesis then stop. Nerve cells, muscle cells,
o Semi mitotic: only divide when injured. Liver cells.
Human bodies consist of
Germ cells: egg, sperm; haploid
Somatic cells: non-gamete cells; diploid
o Matrix: non-cellular, for support
To be a valid theory it must account for: Universal, Progressive, Deleterious (CUPID)
o Programmed Longevity: aging is result of sequential turning off and on of certain
genes. Longevity assurance genes when on increase LE; deleterious genes when
on decrease LE.
o Endocrine Theory: biological clocks act through hormones to control pace of
o Immunological Theory: a programmed decline in immune system functions leads
to increased vulnerability to infectious disease and consequently, death.
o Wear and Tear: vital parts of cells wear out
o Rate of Living: the greater the rate of oxygen metabolism, the shorter the
o Crosslinking: an accumulation of cross-linked proteins damages cells, free
radicals, AGE products (when AGE products bind to receptors (RAGE), they
contribute to some chronic inflammatory diseases) and waste accumulation
(lipofuscin – product of oxidation of unsaturated fatty acids from lysosomes).
o Free Radicals: accumulated damage caused by oxygen radicals causes cells to
stop functioning (unpaired electrons pull electrons off other molecule, causing it
to become a free radical, etc; causes DNA crosslinking which contributes to
cancer and other diseases of aging)
o Somatic DNA Damage: genetic mutations occur and accumulate with increasing
age. Damage to mitochondrial DNA might lead to mitochondrial dysfunction.
Faulty repair to damaged DNA with age; errors in proteins with age.
o The purpose of a species is to prevail by creating progeny so it must maintain
itself through reproduction. There is no need to invest in biological resources
after they have nurtured offspring. When we are most protected and have
lowest death rate is at puberty – when we become reproductive and are able to
pass on genes to offspring. At age ~30, there is no more need to biologically maintain organism so we’ve lost protection, remain neutral, and start to
o Mutation Accumulation: “late-acting” gene because deleterious effects are only
expressed after age of reproduction. Can be an accumulation of mutations or a
mutant gene is turned on. Not selected against because they do not affect
reproduction or nurture the next generation.
o Antagonistic Pleotrophy: Pleotrophy is when a single gene can have multiple
effects. Late-acting genes may exist and have not been selected against because
they have a positive effect early in life. Ex estrogen, ApoE4 (media