THEORIES OF BIOLOGICAL
AGEING

Biological Ageing Theories
Evolutionary Physiological
Programmed Stochastic
intrinsic
timing
chance
events

• Evolutionary theories are more concerned with why
ageing occurs.
Why is a feature of life that is so detrimental to the
organism as ageing maintained by natural selection?
• Physiological theories attempt to explain how ageing
occurs in structures and functions within the body.
• Theories of ageing are often difficult to characterise
because many of them overlap.
• Many of these theories are inter-related
- NETWORK THEORIES

Evolutionary
1) Disposable Body Theory
Once an organism has produced viable offspring its body is
no longer needed, it then ages and dies.
2) Antagonistic Pleiotropy Theory
Certain genes maybe useful in early life but detrimental in later life
3) Accumulation of Late Acting Error Theory
Late acting genes have not been removed because they act after
reproduction

Physiological Theories
Programmed Ageing vs Stochastic Ageing
Programmed theories maintain that ageing occurs
due to intrinsic timing mechanisms and signals
e.g. Genetic Timers
Stochastic theories (i.e. probability theories) maintain
that ageing occurs as the result of chance or
accidental events e.g. Free Radical damage

Physiological
1) Genetic Theories

Physiological
A) Spontaneous Mutation Hypothesis
Normal
protein
production
Abnormal
protein
production

• One of the first serious attempts to explain ageing.
• It proposes that the key events in ageing are mutations
to the DNA.
• These mutations are passed on to successive cellular
generations and lead to incorrect protein, enzyme
formation.
• Genetic mutation play a role in the development of
some cancers.

Physiological
B) Genetic Timers
Genes are used in a specific sequence and govern each stage of the
body’s development and ageing.
• Genetic Clock Theory
Some genes keep track of the body’s progress and in this way control the
age at which certain events occur (Hayflick Limit).
• Death Gene theory
The closing segments in genetic instructions contain genes called
DEATH GENES that tell the body to deteriorate and die.
• Telomere Theory
Cells may keep track of their age by a shortening of their telomeres.

Hayflick’s Limit

C) Limited Gene Usage
There are a limited number of times that the
instructions in genes can be used. Reading the inform-
ation contained within genes somehow changes or
damages them.
The results of this are detrimental changes to the
proteins which are produced.
There are 2 reasons why genes may only be read a
certain number of times:
i) Somatic mutation
harmful factors may damage genes:
- radiation
- toxic chemicals
- free radicals
ii) Faulty DNA repair

2) Error Catastrophe Theory
Damage occurs not to the DNA but to the RNA which spreads damage
across the whole body.
3) Rate of Living Theory
Ageing is caused by the rate of metabolism because the mechanisms of
metabolism cause damage.
Basal Metabolic Rate (BMR)
Basal Metabolic Intensity (BMI) = body mass
 BMI  rapid ageing  shorter lifespan
LIVE FAST DIE YOUNG!

4) Free Radical Theory
What is a Free Radical (FR) ?
FRs are atoms or molecules with an unpaired electron
e.g. 02 + e = *O2
-
(superoxide radical)
Small FRs in the body include:
hydroxyl radical (*OH)
nitric oxide radical (*NO)
Larger FRs contain an organic molecule, R:
alkoxyl radical (*RO)
peroxyl radical (*ROO)

Reactive Oxygen Species (ROS):
ROSs are not FRs but are highly reactive substances:
e.g. Hydrogen peroxide (H2O2)
Peroxynitrite (ONOO
-
)
Peroxynitrite is the fastest acting and most toxic to the
body.

Damage caused by FRs is the main reason for ageing and age
related diseases.
There is no clear idea as to which, if any, of the the many types
of FR are the most important in promoting ageing.
The theory is based upon several observations:
+ve correlations:
metabolic rate vs FR production
age vs “
cataracts vs “
-ve correlations:
mean Longevity vs FR production

FRs damage body molecules by taking electrons from
molecules - oxidation
Oxidation alters the shape of molecules which often
leads to malfunction.
FRs appear to cause damage to DNA, lipids & proteins
FR damage can cause:
- inflammation
- excess blood clotting
- cataracts
- atherosclerosis

To defend against the effects of FRs the body has
mechanisms to eliminate them and to remove and
repair molecules damaged by them.
Substances called ANTI-OXIDANTS destroy FRs by
helping to create pairs of electrons.
Examples of anti-oxidants:
- vitamin E
- vitamin C
- beta carotene
The body also makes its own anti-oxidants:
- melatonin
- albumin
- uric acid

The body also makes enzymes to prevent FR
Production and speed up FR elimination.
Selenium is a vital dietary component as it helps an
enzyme (glutathione peroxidase) remove H2 O2.

5) Mitochondrial Theories
Mitochodrial activity and damage to mitochodria
causes ageing.
Organelles that release
useful energy for cells.
Mitochondrial DNA
(mtDNA) found in the
matrix.
Mitochondria

• Mitochondria are the main intrinsic source of FRs
& ROSs.
• Mitochondria are damaged by FRs
• Mitochondria are susceptible to damage by external
toxins and radiation.
• Cells which no longer divide accumulate damaged
mitochondria
• Mitochondria cannot repair their DNA

5b) Mitochondrial DNA Theory
• mtDNA damage occurs much faster than damage to
nuclear DNA
• mtDNA is not protected by proteins
• damaged mtDNA accumulates in cells
• damaged mtDNA leads to age changes because each
cell uses all of its mtDNA but only about 7% of its
nuclear DNA.
• Effects:
- less energy production
-  FR production
- accumulation of damaged & harmful
molecules

6) Clinker Theories
• Potentially harmful substances accumulate in the body
over the years
• One substance that has been identified is LIPOFUSCIN
• Lipofuscin is a mixture of chemical waste products
from normal cellular activities which becomes
concentrated in the cells of the body e.g. heart and
brain.
• High Lipofuscin concentrations make cells appear
darker in colour – age pigment.
• Accumulation of glucose has also been implicated in
causing age changes – it binds to molecules causing
them to stick together.

6) Clinker Theories (cont’d)
• Another substance that accumulates between cells
with age is a protein called AMYLOID.
• In some disease conditions (AMYLOIDOSIS) its
concentrations become excessive and interferes
with normal organ function.
• Amyloid is found in high concentrations in the
brains of ALZHEIMER’S disease patients.

7) Cross-linkage Theory
• Collagen and other molecules in the body become
linked together with increasing age.
• These cross-linkages are promoted by FRs, glucose
& light.
• Cross links:
-  movement of molecules for reactions
-  movement of materials through the body
-  movement of body parts
• The result or these changes is malfunction and ageing.

8) Wear & Tear Theory
• Ageing is an accumulation of injuries and damage to
parts of the the body.
• Use, accidents, disease, radiation, toxins and other
detrimental factors adversely affect different parts of
the body in a stochastic fashion.
• The Wear & Tear Theory does not account for the
rather regular and universal nature of biological
ageing.

Other Theories
Hormone Theories
• Ageing is caused by hormones secreted by the
endocrine glands. e.g. INSULIN THEORY
Calcium Theory
• Abnormal levels of Calcium lead to inadequate
regulation of adaptive mechanisms.
Immune System Theories
• The ability of the immune system to distinguish
between intrinsic and foreign materials is weakened.
Immune cells will then attack and damage the body’s
own structures.