The document discusses several theories of aging, which are generally categorized as either error theories, where aging results from damage accumulation over time, or programmed theories, where aging follows an internal biological timetable. Specific theories covered include the waste accumulation theory of aging being caused by a buildup of free radical damage, and the mitochondrial damage theory linking aging to reactive oxygen species generated by mitochondria. Programmed theories discussed include the immunological theory of aging being driven by a decline in immune system effectiveness over the lifespan. The rare premature aging condition progeria is also summarized.

1. “Theory of Ageing”

2. What is Aging?
The gradual and spontaneous changes that
occur in maturation from infant to young adult.
These changes create a normal physiologic
decline seen in middle and late adulthood.

3. There are many theories of ageing. In 1990
Mevdevev in an excellent review stated that
there were more than 300 theories of ageing
and the number is increasing.

4. Characteristics of the ageing process.
Theories of Ageing
Jose Vin˜ a1, Consuelo Borra´ s2 and Jaime Miquel3
1Department of Physiology, School of Medicine, University of Valencia
3Department of Biotechnology, University of Alicante, Spain

5. Theories of ageing Classification.
Theories of Ageing
Jose Vin˜ a1, Consuelo Borra´ s2 and Jaime Miquel3
1Department of Physiology, School of Medicine, University of Valencia
2Department of Biotechnology, University of Alicante, Spain

6. Ageing theories, which mainly has been categorise
into two main categories:
 Error theory
Aging is a result of internal or external assaults that
damage cells or organs so they can no longer
function properly.
 Programmed theory
Aging has a biological timetable or internal
biological clock.

7.  Waste Accumulation Theory
 Mitochondrial Damage Theory

8. Waste Accumulation Theory
The human lifespan simply reflects the level of free radical damage
that accumulates in cells. When enough damage accumulates, cells
can’t survive properly anymore and they just simply give up.”
Earl Stadtman (National Institutes of Health)
Recent studies show that cross-linking reactions are involved in the
age related changes in the studied proteins.
The cross-linking theory of aging was proposed by Johan Bjorksten
in 1942. According to this theory, an accumulation of cross-linked
proteins damages cells and tissues, slowing down bodily processes
resulting in aging.

9. Bruce Ames and his co-workers, in California,
have calculated that reactive oxygen species modify
approximately 10,000 bases of DNA per cell.
DNA repairing enzymes are able to repair the vast
majority of these lesions, but not all. Therefore,
DNA lesions that go unrepaired, such as 8-oxo-dG
(DNA damage biomarkers) accumulate with age.
Genetic mutations occur and accumulate with
increasing age, causing cells to deteriorate and
malfunction.

10. RNA molecule is highly susceptible to oxidative stress.
Also the expression of this mitochondrial gene decreases
with age in parallel with the survival curve of Drosophila.
Thus, 16S rRNA can be considered as a Biomarker of
cellular ageing.
Calleja, M., Pen˜ a, P., Ugalde, C., Ferreiro, C., Marco, R., and Garesse, R. (1993) Mitochondrial DNA
remains intact during Drosophila aging, but the levels of mitochondrial transcripts are significantly
reduced. J. Biol. Chem. 268, 18891 – 18897.

11. It is well known that mitochondrial DNA is much
more oxidized with age than nuclear DNA.
In 1996, Scientists showed that oxidative damage to
mitochondrial DNA correlates with oxidation of
Mitochondrial Glutathione.
Reactive oxygen species are continuously generated
in the mitochondrial electron transport chain.

12. Approximately 1 – 2% of all oxygen used by
mitochondria in mammals, does not yield water but
reactive oxygen species.
Boveris, A., and Chance, B. C. (1973) The mitochondrial generation of hydrogen peroxide. General
properties and effect of hyperbaric oxygen. Biochem. J. 143, 707 – 716.
Mitochondria from old animals produce more ROS than
those from young ones.
These authors micro-injected isolated mitochondria from
fibroblasts of old rats into cells of young ones and so the ones
who had received ‘old’ mitochondria rapidly entered
senescence.
Sohal, R. S., Sohal, B. H. et al. (1990) Relationship between antioxidant defenses and longevity in
different mammalian species. Mech. Ageing Dev. 53, 217 – 227.

13. Under the prodding of the antioxidant enzyme Superoxide
Dismutase, toxic and damaging oxygen free radicals,
generated from ongoing cellular reactions, are combined with
Hydrogen Ions to form Hydrogen Peroxide.
To rid itself of hydrogen peroxide, itself a toxic free radical
generator, the cell then employs the talents of two more
antioxidant enzyme systems, Catalase and Glutathione
Peroxidase.
Working together, these enzyme proteins cleave the two
remaining hydrogen peroxide molecules, to produce harmless
water and molecular oxygen.

14. Natural defence mechanisms of free radical damage in cell.

15. The programmed theories imply that aging follows a biological
timetable.
This regulation would depend on changes in Gene Expression
that affect the systems responsible for maintenance, repair
and defence responses.

16.  Immunological Theory
The immune system is programmed to decline over time,
which leads to an increased vulnerability to infectious disease
and thus aging and death.
It is well documented that the effectiveness of the immune
system peaks at puberty and gradually declines thereafter
with advance in age.
For example, as one grows older, antibodies lose their
effectiveness.

17.  Progeria
Progeria is a rare genetic disease, originally described by
johnathan Hutchinson in 1886 and Hastings Gilford in
1904.
Hutchinson–Gilford progeria syndrome (HGPS)
Birth incidence of approximately 1 in 8 million.
In normal conditions, the “LMNA gene” codes for a structural
protein called “prelamin A”.
But in case of Progeria, defective “Prelamin A” is encoded.

18. Normal Nucleus
Abnormal Nucleus of Progeria patient
http://en.wikipedia.org/wiki/Progeria

19. Age and Ageing 1998; 27: 73-80
REVIEW
The premature ageing syndromes: insights into the
ageing process.

20.  Theories of Ageing
Jose Vin˜ a1, Consuelo Borra´ s2 and Jaime Miquel3 1Department of Physiology, School of
Medicine, University of Valencia 3Department of Biotechnology, University of Alicante, Spain
 Calleja, M., Pen˜ a, P., Ugalde, C., Ferreiro, C., Marco, R., and Garesse, R. (1993)
Mitochondrial DNA remains intact during Drosophila aging, but the levels of mitochondrial
transcripts are significantly reduced. J. Biol. Chem. 268, 18891 – 18897.
 Boveris, A., and Chance, B. C. (1973) The mitochondrial generation of hydrogen peroxide.
General properties and effect of hyperbaric oxygen. Biochem. J. 143, 707 – 716.
 Sohal, R. S., Sohal, B. H. et al. (1990) Relationship between antioxidant defenses and longevity
in different mammalian species. Mech. Ageing Dev. 53, 217 – 227.
 Modern Theories of Aging, Lyle MacWilliam , www.macwilliam.net
 http://en.wikipedia.org/wiki/Progeria
 Age and Ageing 1998; 27: 73-80
REVIEW -The premature ageing syndromes: insights into the ageing process.