The Aging Process
The definition of "Aging Process" is a universal change in a species. This change is progressive, irreversible, and deleterious.
Life Expectancy = time it takes for 50% of individuals of a certain species to die out.
Life Span = the length of time an individual lives. Note that this is different than life expectancy. It is influenced, amongst other things, by medical advances and the environment.
Gompertz Curve mathematical correlation of age and survival
- atherosclerosis is an aging process as well as emphysema and osteoarthritis
what if we were biologically immortal, how long would we live? (we would still die due to our environment). Using the Gomperts equations it was calculated that the average life span would be 1,200 years, with a maximum life span of 25,000 years.
Is aging a disease? Yes. Certain diseases demonstrate this by severely compressing the life span: Hutchinson Gilford Disease (die age 12), Werner Syndrome (die at 30-40), Down Syndrome (>40 years).
Three Fundamental Observations:
- According to this theory even if we were to cure atherosclerosis and cancer we would only get a minimal increase in life expectancy (would still die of infections and accidents)
- Further, humans that pass a certain age have a reduced chance of getting certain diseases (malignant neoplasm, etc)
- Evolutionary Biologists refuted this with the argument that it is not possible to study enough people to observe a statistical significance
- As such experiments were done with a huge population of drosophila (fruit flies):
- after a certain age the graph reached a plateau instead of just rising as expected
- demonstrated that some members of the drosophila population reached a life span that exceed the expected by a factor of five
- similar results were achieved with epidemilogic studies of human populations.
With age, vessels and the lungs get stiff. Collagen becomes more and more yellow. Evidence of this is the accumulation of yellow pigment in the lens of the eye with age
Regardless, homeostatic factors dont change with age (pH, temperature, enzymes, etc).
Anything that gets stressed changes, and example of which is the observed decrease in lymphocytes. (note: this may be a good thing because there is an increased risk for autoimmune diseases with age).
- (1) Most definitive age-related changes are found in long-lived tissues such as neurons and lymphocytes.
- (2) Many age-related processes are accelerated by diabetes. Possibly relating to sugar damage (see below).
- (3) Food restriction in animals prolongs life.
- stress increases rate of aging
Theories of Aging
(1) Stochastic Theories random forms of damage, "wear and tear"
(2) Genetically Controlled / Programmed
Cellular aging in vitro: The hayflick phenomenon Telomere Shortening (telomeres at the end of a chromosome get shorter after every division, possibly due to telomerase getting old. This makes the chromosome more susceptible to damage that comes with aging)
Aging genes in c. elegence and drosophila involved with glucose-insulin signaling
Recent studies showed that under metabolic restriction animal metabolism did not go down, but rather remained unchanged or even increased. This could probably be due to more efficient use of metabolic fuels.
- Oxidative Stress / Free Radical Theory damage by O2 radicals.
- Carbonyl Stress / Glycation / Maillard Reaction as mentioned above get brown pigmentation with aging. This is due to sugar residues cross-linking proteins. Recent experiments showed increasing levels of Pentosidine (crosslinked protein) in aging animals, and decreasing levels of Pentosidine in food restricted animals. These sugar crosslinks may have a significant affect on collagen and elastin which become brittle with age due crosslinking of molecules. Brittle collage/elastin = tissues with low compliance.