Aging Lecture 5
Aging Lecture 5
DNA Instability
Fundamental Properties of Cells Lecture 5
Julian Pakay
Weismann dropped this concept and instead suggested that aging evolved
because organisms that segregate germ and soma must invest additional
resources to reproduce instead of maintaining the soma, and this
renunciation of the soma results in aging.
August Weismann – Programmed Cell Death
“death takes place because a worn-out tissue cannot forever renew itself, and
because a capacity for increase by means of cell division is not everlasting but
finite”
Main Idea
Numerous checkpoints to
ensure DNA is accurately
duplicated
• Expression of cyclin/activation
of Cdk
• Phosphorylation of signalling
proteins to enter S phase
p53 helps prevent damaged DNA from being copied
Alexis Carrel (1921) suggested that all cells explanted in culture are
immortal, and that the lack of continuous cell replication was due to
ignorance on how best to cultivate the cells.
Generally believed that all vertebrate cells could divide indefinitely in cell
culture.
The cells were fed with a daily extract of chick embryo tissue.
Cells fed with an extract of chick embryo tissue extracted under conditions that
permitted the addition of fresh living cells to the culture at each feeding.
Measuring life-span in culture
• Grown to confluence
When the male ‘control’ culture stopped dividing, the mixed culture was examined and
only female cells were found. This showed that the old cells ‘remembered’ they were
old, even when surrounded by young cells, and that technical errors or contaminating
viruses were unlikely explanations as to why only the male cell component had died
Life History of Mitotic Cells in Culture
Data From Fetal Fibroblasts For Several Species
• cancer cells
• cell lines
What causes this replicative senescence?
Hayflick’s laboratory showed that the replicometer was located in the nucleus
End Replication Problem
Enzyme (reverse
transcriptase) with protein
+ RNA subunits
Telomeres shorten with age (T cells, tissue with high cell turnover)
Therefore, telomere shortening is a cause of aging
Cycloastragenol is a natural
ingredient extracted in minute
quantities from the root of the
astragalus plant. Its method of
action is to activate the hTERT
gene, thereby activating the
enzyme telomerase
Long-lived animals should have long telomeres
and
Short-lived animals should have short telomeres
Humans 5–15 kb
Mice Up to 150 kb
Rats 20–100 kb
Birds 5–20 kb
Ants 9–13 kb
Telomere length and maximum lifespan in mammalian species
Why might you want limit cell division in a large long-lived species?
How to explain these correlations?
One hypothesis:
but