SUBJECT: PHYSIOLOGY
TOPIC: AGEING
LECTURER: DR. GIGI FRANCISCO
DATE: MARCH 2011
PHYSIOLOGY OF AGEING
AGING – is actually one of the individual’s physiological
processes. Thus it is absolutely NORMAL for one
to experience this.
Notice that as time goes by, the population is
starting to bulk up in the economically productive age, as
well as in the elderly age. This is actually due to the
numerous medical advancements during this period that
helped the entire race extend or improve its longevity.
(Same is true here in the Philippines. During the
20s, 30s, most people died due to TB, because there
was no cure for it during that time. However, shortly at
the latter part of the same period came the advent of
antibiotics. From then on, infections were easily cured,
thousands of lives were saved and there was an
obvious decrease in mortality. This caused us to slowly
experience a stable population pyramid, wherein there
is a steady mortality rate, indicating that more people
are bound to die as they get older. Please check the
ppt. The image is not that clear.)
PHYSIOLOGY: AGEING
This particular graph shows us the number of
deaths occurring on a particular age group. It suggests a
high number of deaths at birth. Also, during the first decade
of our lives, there is a marked decline in the number of
deaths. After this steep decline comes a progressive
increase in deaths, which occurs starting the second
decade of our lives, until we grow old.
Therefore, we are all bound to get old. Hahaha.
IS AGEING A DISEASE? SHOULD WE FIGHT AGEING?
BEFORE THAT, LET US CLASSIFY AGEING FIRST.
o PRIMARY AGEING – intrinsic, physiological changes
brought about by TIME.
o SECONDARY AGEING – changes that result from the
interaction of the natural, physiological ageing (PRIMARY)
and stress from the environment, which includes
DISEASE.
However, the elderly will be more vulnerable to certain
disease processes. These disease processes are the main
concern of the medical science.
Page 1
MECHANISMS OF AGEING
o DAMAGE DUE TO OXIDATIVE STRESS AND OTHER
MACROMOLECULES
 Sources of Oxidative Stress
- Reactive Oxygen Species (ROS), which are mainly by-
products of cellular metabolism.
- The most common source of these ROS is the
Mitochondria, where the Electron Transport Chain
happens.
- As the ETC proceeds, it releases the most common
free radical in the body, known as superoxide.
However, our body has its own defense against these
substances, in the form of an enzyme, Superoxide
Dismutase, that will reduce the damage done by this
molecule to the body by converting it to hydrogen
peroxide.
- After this, the hydrogen peroxide generated will be
converted to water and molecular oxygen, by another
part of this defense system, the enzyme Catalase.
- An alternative defense mechanism, Glutathione
Peroxidase also acts on hydrogen peroxide in a redox
reaction, by converting (reducing) it to water, and
having an oxidized glutathione as by-product.
o INADEQUACY OF REPAIR
- Also, Vitamins C and E help in the detoxifying of
these radicals.
- What happens is that, as a kid, these defense
mechanisms are well-oiled and efficient; therefore
they are able to keep up with all the ROS produced
by metabolism. Cells are continuously protected and
these radicals fail to affect our body.
- However as we age, these systems gradually become
inefficient and damaged, therefore producing less
defensive action towards these harmful radicals.
- An imbalance now sets in between the production of
ROS (higher), and the processing/detoxification of
these radicals (lower). As more of these radicals are
produced, our cells receive more damage and start
to decline in function. This damage is what we term
oxidative stress. More oxidative stress = ageing.
(Damage due to various Macromolecules)
 Glycation and Glycoxidation
- Reaction/interaction of Glucose and Macromolecule
(protein/DNA)
PHYSIOLOGY: AGEING
- This reaction produces AGEs, Advanced Glycation
End-products.
- These AGEs cause damage by altering the structure
of various proteins/enzymes, which would eventually
lead to the disruption of its function.
- In a deeper aspect, AGEs inflict harm through a
process called “cross-linking” that causes
intracellular damage and apoptosis.
- This serves as the basis for the GLYCATION
HYPOTHESIS OF AGEING by Anthony Cerami
- It states that LEVEL OF GLYCEMIA = EXTENT OF
GLYCATION/ PRODUCTION OF AGEs
- Eg. (AGEs in proteins) altered structure/function,
opacity of lens in diabetics (lead to cataract
formation), stiffness of collagen in blood vessels
(decrease in arterial compliance and distensibility)
 Mitochondrial Damage
- Since this is the major source of ROS, this is also the
major target of damage.
- Basis for the MITOCHONDRIAL THEORY OF AGEING.
- It states that oxidative damage to the mtDNA
(mitochondrial) reduces its efficiency and capability
to generate ATP, which translates to an eventual
decline and loss of function and afterwards, ageing.
 Somatic Mutations
- Damage to (genomic) nuclear DNA and mtDNA, due
to constant exposure to radiation, toxic chemicals
from the environment, plus oxidative stress.
- When DNA is damaged, failure of DNA
replication/transcription occurs. This would all boil
down to disruption of normal function, which leads to
ageing.
- Basis for the DNA DAMAGE THEORY OF AGEING
- Similarly, it states that accumulation of DNA damage
interferes with DNA replication/transcription. This
would cause impairment of function and thus, ageing.
Although oxidative stress can cause DNA
damage, it is not clear whether or not DNA damage is
sufficient to cause the functional deterioration that
characterizes ageing.
 DNA Repair
- Every time your cell undergoes replication, there are
minor mutations that take place, due to the
imperfections in the DNA, but more importantly due
to external hazards that affect this process.
- However, we do not manifest any form of DNA
damage immediately, because our body has its own
way of counter-acting these mistakes. (Immune
system quickly destroys malfunctioning
cells/potentially dangerous proteins resulting from
incorrect DNA replication)
- As time goes by, these protective mechanisms
weaken, thus not all mistakes/malfunctioning cells
or proteins are corrected/ eliminated by our
defenses.
- Basis for the DNA REPAIR THEORY OF AGEING
- It states that DNA repair mechanisms decline with
age, and as these mechanisms do so, our body
allows the proliferation of harmful cells/ proteins that
resulted from the minute DNA replication mutations.
More harmful cells/proteins = ageing.
 Protein Turnover
- Proteins constantly participate in various metabolic
reactions taking place within the body.
Page 2
 - As they do so repetitively, their 2O structure (certain continuous replication. It is these telomeres that
sub-configurations and motifs, eg. Alpha-helix) and give an “allowance” at the ends, so that the coding
3O structure (3-D model of protein, stabilized by regions of the DNA will be preserved despite
hydrophobic reactions and salt bridges, S-S/disulfide replication. As the ends of the telomere get
bonds) could possibly be affected. *biochem review. chipped off slowly, the replicating capacity of the
Haha* cell also decreases, due to its dependency to the
- Remember, once protein structure is affected, telomeres. When these ends become very short
function comes next. Loss of function of proteins already, the cell becomes incapable of cell division.
would lead to ageing. - This major role of the telomere is the reason why it
- Protein turnover (replacement of new ones), is implicated to be the factor that affects the pre-
decreases with age. Abnormal proteins accumulate, determined amount of cell divisions a cell can
because they can’t be replaced with new ones. undergo. The length of these telomeres can
provide a glimpse of the capacity of a particular
 Membrane Deterioration cell to divide.
- Polyunsaturated fatty acids in the membrane are
also under oxidative stress, which then produces
lipid peroxides.
- These Lipid Peroxides change the character and
affect the integrity of the cell membrane.
- There is an increased amount of Cholesterol, which
leads to a higher CHOLESTEROL: PHOSPHOLIPIDS (in
membrane) ratio.
- More cholesterol in the membrane means the
membrane becomes more congested, or rigid
(nagsisiksikan sila), thereby decreasing membrane
fluidity.
- All in all, these changes interfere with membrane
function – barrier, transport of substances and cell
signalling.

Please do remember that all of these defective

processes occur frequently in the elderly, compared to - This theory strongly applies to most of the body cells;
the younger ones, where sometimes, some of these however there are still minute exemptions to this.
defective mechanisms do not even apply. (Skin, gametes and germ cells)

 Cell Removal
o DYSFUNCTION OF HOMEOSTASIS OF CELL NUMBER - Apoptosis (programmed cell death)
- Dysregulation of the process of apoptosis would lead
 Hyperplasia to ageing.
- An increase in cell number; where hyperplasia - There would be failure to remove damaged cells.
occurs, there is an enlargement in organ/tissue. (Which are normally removed via apoptosis)
- The prostate gland is normally a hyperplastic organ - While an abnormal increase in apoptosis, would
in an ageing male, although it can still cause eventually cause a decrease in cell number. (eg.
problems in urination. Brain, starts at the AGE OF 30! O.o)
 Neoplasia
AGEING IN PHYSIOLOGICAL SYSTEMS
- More common for the elderly
- Formation of new and abnormal cells; common
cause of cancer in the elderly. (loss of deregulation
of mitosis)

From these concepts arise a few more mechanisms:

 Limitations of Cell Division

- Experiment was conducted, wherein they cultured
a generation of fibroblastic cells and observed how
many generations of cell division can these cells
perform, provided with a good nutritional supply.
- At the end of the experiment, they found out that
cells started to stop undergoing cell division.
- Therefore, each cell can only undergo cell division
according to its pre-determined amount/level.
- Remember, each cell has a pre-determined
amount of cell divisions it can perform.
- Called the Hayflick Limit of Cell Division
- By Leonard Hayflick and Paul Moorehead
- Role of Telomeres in cell division, by Calvin Harley
- Telomeres are regions of repetitive DNA found at
the ends of chromosomes that protect these ends
from deterioration.
- If not for these telomeres, the ends of the
chromosomes would be eliminated upon

PHYSIOLOGY: AGEING Page 3

 More important than knowing the items, is
noting what the trend is. All of the body parameters
mentioned, (conduction velocity, basal metabolic rate…)
are all set to decline some point in our lives.
o LOSS OF HEIGHT
 We will all shrink.
 Women start to shrink at the age of 20. Peak height at
the age of 15-16.
 Men start to shrink at the age of 25. Peak height at age
18.
 Due to the compression of the cartilaginous disk and
eventual loss of integrity of vertebral bones.
o DECREASE IN LEAN BODY MASS
 Increase in adipose tissue mass, even in active, sporty
individuals.
 Changes in the metabolism (decline in metabolism),
then causes a change in the proportions of adipose
tissue in the body.
 Redistribution, accumulation of body fat (visceral and
abdominal cutaneous tissue)
o SKIN
 Epidermis thickness decreased; this causes a decrease
in melanocytes, which in turn causes decreased
protection against UV radiation. (elderly are more prone
to skin cancer)
 Dermis, decreased collagen and elastin. (loss of skin
elasticity)
 Treatment via Retinoic Acid simply causes an
inflammation reaction, which, after some time will
subside and you will return to your original skin again.
 Decreased sweat glands and sebaceous glands.
 Decreased melanocytes in hair cells. Means more gray
hair.
o SKELETAL MUSCLE
 Decrease in muscle mass, progressive atrophy of
muscles
 Gross Sarcopenia, a decrease in muscle mass, sets in.
 This is all due to inactivity, and the loss of innervation
of these muscles (loss of type II motor neurons, which
naturally degenerate in time)
 Causes decrease in fine motor control
 Reduction in overall muscle strength.
o BONE
 Osteoporosis, wherein bone resorption exceeds bone
formation (loss of bone mass)
 Increased risk of bone fractures; basic rule: elderly
should not fall.
 Contrary to popular belief, both BOYS and GIRLS are
affected. The more dramatic effect only seen in girls
due to the effects of menopausal period.
 Even if bone density is improved by medicine, there are
still evidences that suggest sustained bone fractures,
which usually occur at the head of the femur.
o SENSORY FUNCTIONS
 Decline in all of your sensory functions.
 Decreased touch sensitivity, vibratory sense and two-
point determination
 Hearing
- Presbycusis, loss of hair cells in the organ of corti
 Vision
- Presbyopia, decreased lens elasticity and loss in
power of accommodation
- Possible diseases: cataract and glaucoma
 Taste
- Deterioration of the ability to discriminate tastes
 Olfaction, reduced.
PHYSIOLOGY: AGEING
 TASTE and OLFACTION AGEING would result to “blunt-
tasted food”.
o MOTOR FUNCTION
 Decrease/slowing of reaction time, which is reflective
of;
 Decrease/slowing of central processing
 Posture and balance deteriorates
o COGNITIVE FUNCTION
 Intelligence, memory and learning
- DECLINE IS NOT SIGNIFICANT.
- Trouble could be present in recent memory but they
do not unlearn things.
- Slowing of central processing, but still capable of
learning new things.
o CARDIOVASCULAR FUNCTION
 Decreased arterial compliance, consequent increase in
peripheral resistance
- Cause an increase in systolic pressure
- Therefore, increase in afterload; can cause left
ventricular hypertrophy in elderly
 Postural hypotension
- Blunting of the baroreceptor reflex, where
baroreceptors, which are supposed to quickly sense
the change in blood pressure upon rising from bed,
are not able to do so.
- This inhibits the elderly from jolting out of the bed
and running towards somewhere upon waking up,
unlike us, where we can easily scram and run to
school when we are 5 minutes away from the start of
our Physio class. O:D
o PULMONARY FUNCTION
 Decrease in lung volumes
 Decline in maximal oxygen intake
 Decrease in strength and endurance of respiratory
muscles, which lead to a lower response to physical
conditioning/ exercise with age.
 THIS DOESN’T MEAN YOU CAN’T EXERCISE ALREADY.
You simply have to limit yourself even more due to your
physical incapability.
o RENAL FUNCTION
 Less response to Na+ load
 Less ability to concentrate/dilute urine
 Impaired secretion of K+, Acids
 DECREASED BLADDER CAPACITY AND COMPLIANCE;
results in premature contraction even if not yet full.
 This is the reason behind the main concern of elderly-
urine incontinence.
o GASTROINTESTINAL FUNCTION
 SECOND MOST COMMON cause of hospitalization for
the elderly
 However, if this stays healthy, it will seem like a GI tract
of any young, healthy individual.
 Common problems: motility, chewing (due to presence
of dentures), swallowing (due to the weakening of the
muscles responsible for involuntary swallowing) and
constipation (due to the less response of colonic wall to
distension, therefore it stacks up so much/naiipon)
CAN WE DEFER AGEING? YES!
Despite the fact that we will all reach this stage
in life, we can somehow do something to delay its
onset.
Page 4
 THEREFORE, AGEING DEPENDS ON YOUR GENES.
This is not completely modified or affected by the
intake of various substances.
MAINTAIN A HEALTHY LIFESTYLE, EXERCISE AND
DIET.

AGEING IS A NORMAL PROCESS.

AFTERALL, WE DON’T HAVE TO LOOK YOUNGER
TO DO THE THINGS WE ENJOY.

-------------------------------------------------------------ENDofTRANX
A research conducted, wherein 2 sets of mice
are fed differently, one fed continuously (ad libitum), Goodluck Batch 2014! HAPPY SUMMER!
while the other one was fed in a controlled manner, SUMMMER NAAAAAA! WOOOOOOOOOOO!
60% of the total diet of the ad libitum mice.
The research shows that the mice with a
controlled diet outlived the mice that had unlimited
supply of food.
They started to link caloric restriction to an
increase in lifespan.

o CALORIC RESTRICTION
 Retards growth (still unsure though)
 Decreases oxidative stress, due to decrease in
metabolism, decrease in production of ROS.
 Decrease in caloric intake causes decrease in uptake
of insulin, decrease in insulin-like growth factors and
insulin-like signals, would all boil down to a lower blood
sugar, where less glycation/glycosylation reactions
happen.
 In this case, you are simply decreasing the occurrence
of all the harmful reactions we talked about (in the 2 nd
page of this handout)
o ANTI-AGEING MEDICINE aka MAGIC BULLETS
 Vitamins C and E
 AAs: Methionine
 Hormones: Melatonin, DHEA, Estrogen, Testosterone,
GROWTH HORMONE
- Researchers conducted an experiment wherein mice
were genetically modified, removing the gene for the
GH receptor. The mice without GH receptor didn’t
react to the hormone, therefore produced less
growth yet a longer lifespan.
 HOWEVER THERE IS NO CREDIBLE EVIDENCE THAT
THESE WORK 100%.
 CAUTION! WE ARE NOT AWARE OF THE LONG-TERM
EFFECTS OF THESE SUBSTANCES.

(Clinical)
o PROGERIA
 Rapid ageing in young people.
 15 year old person that looks like (functions like, works
like, body is actually like) a senior citizen.
 And they actually die because of the diseases that
occur commonly in the elderly.

PHYSIOLOGY: AGEING Page 5