PATHOLOGY OF AGING Michelle Magid
{a 2nd year med
student, whose site I could not find again} What is Biological
aging? Ex. At 20, a top athlete is #1 in the world at his sport. At 35, he is #150. What happened? Ans.
He underwent BIOLOGICAL AGING.
Biological aging is not the same as disease. What is the cause of Biological aging?
Ans. Unknown
As aging proceeds, the ability to ADAPT becomes impaired. If we could eliminate all premature
deaths, we would all still die at about 85. MAXIMUM LIFESPAN IS NOT CHANGED BECAUSE WE WILL ALL UNDERGO BIOLOGICAL AGING.
Trends: Life expectancy in the US has increased for children under 2, increased for people age 30-40, but has
barely increased for people of about age 75. Why??? We have combated birth complications leading to death of babies,
and we can treat illnesses leading to death of middle-aged adults, but we CANNOT GET RID OF BIOLOGICAL AGING.
All organ
functions and abilities decrease with age. Ex. At age 25, we have 6% bone mineral. At age 70, we have 5% bone mineral.
Thus, as we get older, we are naturally more likely to get osteoporosis. Ex. An aged mouse will not be able to adapt to
increased cold stress. It's heart will slow down, it won't shiver as much etc? thus it will get sick and die.
A younger mouse will be able to ADAPT better to stressful environments. Ex. As we age, our vascular system doesn't adapt
as well. Ex-our blood pressure rises as we get older. Ex. As we age, we cannot ADAPT to increased blood sugar (our
blood sugar concentrations will show increase in a cortisone glucose tolerance test.) Ex. Females are born with 733,000
oocytes. At about age 15, they have 389,300 oocytes. At age 45, they only have 10,900 oocytes. Although some of
the oocytes are lost in the menstrual cycle, most of the loss of oocytes is due to Biological Aging in the Ovary.
THEORY:
IS BIOLOGICAL AGING DUE TO ENVIRONMENTAL STRESS (ex. Radiation)? Two mice strains were examined. The strain with
more chromosomal abnormalities had a shorter lifespan. It was thought that more environmental stress= more chromosomal
damage=more biological aging= decreased lifespans. This theory hasn't held up. If this theory were true, pilots,
who are exposed to radiation, should have decreased lifespans, but they don't.
THEORY: IS BIOLOGICAL AGING DUE TO LIPOFUSCIN
ACCUMILATION? Lipofuscin increases with age. Caused by lipid peroxidation (by free radicals for ex.). The accumulation
of lipofuscin= Biological aging. Lipofuscin build-up is a good indicator of free radical oxidation damage being done
to cells. Cells get rid of free radicals via various mechanisms. If the radicals aren't destroyed, they will slowly
cause cell damage. This may be a factor in Biological aging.
THERE IS A STRONG GENETIC COMPONENT TO BIOLOGICAL
AGING> Ex. Non-identical twins have a much larger difference in lifespan than identical twins. Regular siblings
have a larger difference in lifespan than non-identical twins. A genetic component may be DNA repair mechanisms.
If you increase the amount of DNA repair enzymes, you will increase your lifespan.
HAYFLICK PHENOMENON- normal fibroblasts
will grow and divide in a cell culture, BUT at some point, the cells will stop growing (ex at about fifty doublings) regardless
of nutrients etc? This is a normal process. (Side note: if you transform the cell with radiation or something, the cell becomes
immortal and will NOT stop growing after 50 doublings. Cell is actually cancerous. This is not a normal process) Is
Biological aging merely due to the cessation of cells dividing? Ans: Probably not. Aging takes its greatest toll
on cells that DON'T divide (terminally differentiated cells) such as brain cells. Aging is not as relevant with continuously
dividing cells such as fibroblasts and Gastric mucous cells. However, there IS a correlation between lifespan and population
doublings in vitro. Hmmmm?.
DISEASES: Progeria and Werners- Children age very quickly. They are bald and wrinkled by
age 12. The fibroblasts of these sick children have a fibroblast doubling of about 5, not 50. Again, there is a correlation
between lifespan and population doublings of dividing cells.
There is also something about chromosome 1 that has to
do with biological aging. We are not sure what it is, but it adds evidence that there is a genetic component to Biological
aging.
There is a progressive shortening of chromosomes with each chromosomal replication. You reach a point
where the shortening of chromosomes infringes upon the CODING SEQUENCES in the gene. Thus, the loss of coding sequences
may lead to or cause biological aging. TELOMERASE prevents the shortening of chromosomes with replication. Coincidentally,
there is a lot of telomerase in cancer cells. Perhaps increased telomerase in a person hinders biological aging, but
may also cause cancer.
If we could eliminate all premature deaths, we would all still die at about 85. MAXIMUM
LIFESPAN IS NOT CHANGED BECAUSE WE WILL ALL UNDERGO BIOLOGICAL AGING.
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