GENETIC
CONTRIBUTIONS
TO AGING
AGING
Aging affects physiological functions and can be defined as
the accumulation of damage in molecules, cells and tissues
over a lifetime
This often decreases an organism’s capacity to maintain
homeostasis in stress conditions, and entails a greater risk
for many diseases (cancer, cardiovascular and
neurodegenerative disorders) and premature mortality
Aging is a multifactorial process that is determined by
genetic and environmental factors
GENETIC CONTRIBUTIONS
TO AGING
At the cellular level, the most prominent event in an aging
tissue is cell senescence, it is characterized by gradual
accumulation of DNA damage and epigenetic changes in
DNA structure that affect correct gene expression and lead to
altered cell function
The genetic theory of aging states that lifespan is largely
determined by the genes we inherit
According to which, our longevity is primarily determined at
the moment of conception and is largely reliant on our
parents and their genes
FACTORS IN GENETIC
CONTRIBUTIONS
Telomeres
Longevity Genes
Cell Senescence
Stem cells
Epigenetics
FACTORS IN GENETIC
CONTRIBUTIONS
Telomeres - At the end of each of our chromosomes lies a
piece of "junk“ DNA
Telomeres do not code for any proteins but appear to have a
protective function, keeping the ends of DNA from attaching
to other pieces of DNA or forming a circle
Each time a cell divides a little more of a telomere is snipped
off
Eventually there is none of this junk DNA left, and further
snipping can damage the chromosomes and genes so that
the cell dies
In general, the average cell is able to divide 50 times before
the telomere is used up
FACTORS IN GENETIC
CONTRIBUTIONS
Longevity genes - are specific genes that are associated with
living longer
Two genes that are directly associated with longevity are
SIRT1 (sirtuin 1) and SIRT2
Cell senescence - refers to the process by which cells decay
over time
This can be related to the shortening of the telomeres or the
process of apoptosis (or cell suicide) in which old or
damaged cells are removed
FACTORS IN GENETIC
CONTRIBUTIONS
Stem cells - Pluripotent stem cells are immature
cells that have the potential to become any type of
cell in the body
It is theorized that aging may be related to either
the depletion of stem cells or the loss of the ability
of stem cells to differentiate or mature into
different kinds of cells
FACTORS IN GENETIC
CONTRIBUTIONS
Epigenetics - refers to the expression of genes, a
gene may be present but can either be turned on
or turned off
We know that there are some genes in the body
that are turned on for only a certain period of time
The field of epigenetics is also helping scientists
understand how environmental factors may work
within the constraints of genetics to either protect
or predispose to disease
EVIDENCE BEHIND
THE THEORY
The strongest evidence in support of the genetic
theory is the considerable species-specific
differences in maximal survival, with some species
(such as butterflies) having very short lifespans,
and others, such as elephants and whales, being
similar to ours
Direct measurements of telomere length have
shown that telomeres are vulnerable to genetic
factors that can speed up the rate of aging
EVIDENCE AGAINST
GENETIC THEORIES OF
AGING
One of the stronger arguments against a genetic theory of
aging or a "programmed lifespan" comes from an
evolutionary perspective
It's also clear from what we know about lifestyle and disease
that there are many other factors in aging
Identical twins may have very different lifespans depending
on their exposures, their lifestyle factors (such as smoking)
and physical activity patterns
EVOLUTIONARY
IMPLICATIONS
Many evolutionary biologists consider senescence to be the
default state occuring after the animal has fulfilled the
requirements of natural selection
After its offspring are born and raised,the animal can die
E.g. Pacific salmon Recent studies indicate that there are
genetic components that regulate rate of aging
Altering activity of these genes can alter lifespan of an
individual.
EVOLUTIONARY
IMPLICATIONS
The maximum lifespan is a characteristic of a species; It is
the maximum number of years a member of species has
been known to survive
Life expectancy is not a characteristic of species, but of
populations It is the age at which half the population still
survives
Specific gene combinations (genotypes) determine lifespan:
remarkable changes in duration are observed as a result of
alteration in a single gene
EVOLUTIONARY
IMPLICATIONS
One main classes have been described of lifespan-extension
mutants in Caenorhabditis elegans
The class is related to hormone mechanisms of the
insulin/IGF-I signaling (IIS) pathway, such as daf-2 and age-
1 mutants which extend lifespan in worms, flies and mice
But is this sort of insulin signaling critically involved
in longevity in humans as well?
EVOLUTIONARY
IMPLICATIONS
One clue to the hormone pathway's importance is that it has
been conserved through evolution
Another clue is the role that the insulin pathway plays in
diseases like diabetes and cancer
e.g. insulin resistance at the cellular level is a key feature of
type II diabetes
Mutations along the pathway that insulin/IGF-1 receptors put
into motion have been associated with the dysregulation of
growth that characterizes cancer
The disease idea is especially tantalizing, as the risk of both
diabetes and cancer increases with age
TO REDUCE THE GENETIC
AGING OF CELLS
Exercise
Eat a healthy diet
Reduce stress
Avoid carcinogens
Maintain a healthy weight
Thank you!
Any questions?
