There are several major theories that attempt to explain the biological process of aging: 1) Evolutionary theories propose that aging occurs because natural selection favors traits that benefit reproduction early in life, rather than maintenance of the body later in life. 2) Physiological theories explore the molecular mechanisms of aging, such as the idea that genetic programs control aging or that damage accumulates over time due to free radicals or errors in cellular maintenance. 3) Stochastic theories maintain that aging results from random chance events or environmental insults, rather than programmed processes. The document discusses several specific theories under each of these broad categories.

1. THEORIES OF BIOLOGICAL AGEING

2. Biological Ageing Theories Evolutionary Physiological Programmed Stochastic intrinsic timing chance events

3. • 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

4. 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

5. 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

6. Physiological 1) Genetic Theories

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

9. • 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.

10. 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.

11. Hayflick’s Limit

12. 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

13. 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!

14. 4) Free Radical Theory What is a Free Radical (FR) ? FRs are atoms or molecules with an unpaired electron e.g. 0 2 + e = *O 2 - (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)

15. Reactive Oxygen Species (ROS): ROSs are not FRs but are highly reactive substances: e.g. Hydrogen peroxide (H 2 O 2 ) Peroxynitrite (ONOO - ) Peroxynitrite is the fastest acting and most toxic to the body.

16. 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

17. 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

18. 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

19. 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 H 2 O 2 .

20. 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

21. • 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

22. 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

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.