“Theory of Ageing”

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.

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.

Despite recent advances in molecular biology and genetics, the mysteries that control human lifespan are yet to be unravelled.

Characteristics of the ageing process.

Theories of AgeingJose Vin˜ a1, Consuelo Borra´ s2 and Jaime Miquel31Department of Physiology, School of Medicine, University of Valencia3Department of Biotechnology, University of Alicante, Spain

Theories of ageing Classification.

Theories of AgeingJose Vin˜ a1, Consuelo Borra´ s2 and Jaime Miquel31Department of Physiology, School of Medicine, University of Valencia2Department of Biotechnology, University of Alicante, Spain

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.

Waste Accumulation Theory

Mitochondrial Damage Theory

Error theory

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.

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.

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.

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.

Mitochondrial Damage Theory

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.

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.

Modern Theories of Aging, Lyle MacWilliam , www.macwilliam.net

Natural defence mechanisms of free radical damage in cell.

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.

Programmed theory

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.

Programmed theory

ProgeriaProgeria 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.

Disease Associated

Normal Nucleus

Abnormal Nucleus of Progeria patient

http://en.wikipedia.org/wiki/Progeria

Age and Ageing 1998; 27: 73-80REVIEWThe premature ageing syndromes: insights into 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

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.

References