Download File - BIOLOGY and HONORS PHYSIOLOGY Mr. Wylam

Why We Grow Old and Die
SECTIONS
1. The Aging Process: Basics
2. The Cell Cycle and Mutation
3. Stem Cells, Gene Activity and
Methylation Sites
4. Telomere Degradation
5. Interaction with Our Environment
6. Aging Anomalies and Extending
Human Life
KEY QUESTION:
• When DNA from these individuals are compared side by
side, only 1.15 bases out of a thousand are different. Yet
given this striking similarity, one human’s life is just
beginning, while the others is coming to an end…
….WHY?
AGING BASICS
• The average human is composed of
100 trillion cells. Cellular Senescence
or biological aging is the gradual
deterioration of lifeforms at the cellular
level, that results in mortality.
• The word "senescence" essentially
refers to the phenomenon in which
normal diploid cells cease to divide.
AGING BASICS (CONT.)
• fibroblasts (connective tissue cells that
generate pliability in the skin) can reach
a maximum of 50 cell divisions before
becoming senescent.
• Neurons are innately senescent. While
some other cells divide thousands of
times.
• Erythrocytes never divide.
• An array of senescence exists among
the thousands of cell types in the human
body, yet they’re governed by a few
natural phenomenon…
THE CELL CYCLE AND MUTATION
• Cells are governed by the
Cell Cycle, which,
depending on cell type,
will determine if a cell
divides or undergoes
apoptosis (programmed
cell death). Often times
this is appropriate, but in
damaged cells usually
happens prematurely.
THE CELL CYCLE AND MUTATION
• Mutations (random errors in
DNA replication) build up every
day in any organism….the
product of the numerous cell
divisions that keep us alive.
• Although the vast majority are
harmless, some can disrupt the
cell cycle…
THE CELL CYCLE AND
MUTATION
• Although governed by 50+
“proofreading” enzymes that
continuously patrol our newly formed
DNA, “Free radicals” and random
errors persist and are preserved in the
genome….
• Mutations in the genes that code for
the proofreading enzymes themselves
are particularly deleterious.
THE CELL CYCLE AND MUTATION:
THE END GAME
• Apoptosis occurs prematurely or
inappropriately in cells with altered
genes. Mutations trigger regulatory
enzymes which not only inhibit
expression, but illicit a cascade of
events which will kill the cell and
prevent it from replicating.
• Over time, mutations accumulate in our
genome. Apoptosis is more pervasive,
cell functionality decreases, and
senescence abounds.
STEM CELLS
Stem cells are essentially
generic ‘starter cells. They
are “pluripotent” meaning
have the potential to develop
into different cell types in the
body. When division occurs,
subsequent cells can remain
as stem cells, or under
certain conditions become a
specific cell type.
STEM CELLS
• Stem cells decrease as we age,
although even the all adults
retain stem cells in spinal tissue
and Hematopoietic tissue
within red marrow.
• Although Embryonic stems cell
research is controversial, the
potential for their use in tissue
regeneration is exceptionally
promising.
MHC = Mesenchymal Stem cells
GENE ACTIVITY AND METHYLATION SITES
• DNA methylation is a
process by which methyl
groups are added to
DNA on cytosine
monomers. Methylation
modifies the function of
the DNA, typically acting
to suppress
gene transcription
Gene
Activity
and
Methylation
sites
GENE ACTIVITY AND METHYLATION SITES
• Although every person's DNA
remains the same throughout
their lives, gene expression
functions differently as we age.
• Changes appear in DNA
methylation patterns as we
grow older, scientists believe
these act as a "secondary
code" on top of our DNA that
lock genes in the “on” or “off”
position, governing their
expression.
TELOMERE DEGRADATION
• Telomeres represent portions of
DNA and protein present at the tips
chromosomes.
• Telomeres prevent them
chromosomal degradation and endto-end fusion during cell division.
Mammalian DNA consists of the 6
base sequence “TTAGGG”
repeated thousands of times.
TELOMERE DEGRADATION
• The enzymes associated with DNA
replication cannot function at the very
tips of chromosomes, therefore, tiny
portions of our chromosomes are left
every time a cell divides.
• As a result, these non-coding regions
become shorter and shorter as cell
divisions increase accumulate over
time. Eventually, senescence becomes
inevitable.
INTERACTION WITH OUR ENVIRONMENT
• Human behaviors can accelerate the
rate of mutation within our genes,
subsequently increasing the
likelihood of apoptosis and cancer.
• More generally, “overworking”
specific organs in various capacities
can result in failure and premature
death.
AGING ABNORMALITIES
• While a number of factors limit the
lifespans of different organisms,
some have evolved remarkable
genetic mechanisms which extend
life considerably.
• In particular scientists have focused
on mapping the genomes of
Bowhead whales and Galapagos
tortoises. These animals can live
over 200 years and 170 years
respectively.
AGING ABNORMALITIES
• Although slower metabolic rates
within the cells of these
organisms slows senescence.
Over a dozen unique genes have
been discovered within their
respective genomes which repair
DNA, and regulate the cell cycle
much more efficiently (as
compared to similar vertebrates),
extending life considerably.
Link:
http://www.slate.com/articles/health_and_science/science/2015/01/longest_living_mammal_on_earth_bowhead_whale_s_genome_giv
es_clues_about.html
DID YOU KNOW?
• A koi fish named Hanako holds the record as the
longest lived vertebrate in recorded history. Dying at
the age of 226 years. Hanako was born in 1751, and
died in 1977.
EXTENDING HUMAN LIFE
• Modern health and hygiene, coupled
with significant advances in
medicine have extended human life
dramatically over the last 200,000
years.
• Although still the stuff of science
fiction, the potential for transgenic
advances capable of extending
human life are quite real…