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Aging
Prepared by BESTARD,JOAQUIN ANTON
Christiaan Leeuwenburgh, Ph.D
Biochemistry of Aging Laboratory
College of Health and Human Performance
Center for Exercise Science, College of Medicine
Webpage: http://grove.ufl.edu/~cleeuwen/
E-mail: cleeuwen@ufl.edu
Introduction
Aging:
Process that occurs in the lifespan of every creature.
Involves every molecule, cell, and organ in the body.
Unlike senescence it includes problematic and non-
problematic changes in the body.
Senescence:
Progressive deterioration of many bodily functions
over time.
Negative factors of aging.
Aging Introduction
Difference Between Life Expectancy and
Lifespan
Life Expectancy: Average number of years a body is
expected to live.
Maximum Lifespan: Greatest age reached by any member
of the species.
Mean Lifespan Theories of Aging
Programmed Theories:
Programmed Longevity: Aging is the result of the
switching on and off of certain genes that cause
senescence.
Endocrine Theory: Biological clocks act with
hormones to control the pace of aging.
Immunological Theory: Programmed decline in the
immune system functions leading to infectious
disease and thus aging and death.
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Theories of Aging
Damage/Error Theories:
Wear and Tear: Cells and tissues have vital parts that
wear out.
Rate of Living: Lifespan is inversely proportional to an
organisms rate of oxygen basal metabolism
Cross-linking: Bodily processes are slowed by the
accumulation of cross-linked proteins that damage
cells and tissues.
Free Radicals: Accumulation of oxygen free radicals
damages cells and eventually organs.
Somatic DNA Damage: Genetic mutations occur and
accumulate with age, causing cells to malfunction.
Damage to mitochondrial DNA leads to mitochondrial
dysfunction.
Genes and Longevity
Replicative Senescence:
Process occurring at the cellular level.
Cells cease to divide, but they continue to respond to
hormones and other stimuli until they die. (This only
applies to cells in test tubes in vitro)
Brain cells are an example of cells with low
replicative capacity, they reach replicative
senescence after a few divisions.
Genes and Longevity
Hayflick Limit:
Number of times cells can divide before they reach
replicative senescence (in vitro).
The higher the Hayflick limit in the cells of an
organism the longer the lifespan of that organism.
Most cancerous cells do not seem to have a Hayflick
limit since they divide forever in vitro.
Genes and Longevity
Effects of Replicative Senescence on the
Cell:
Cells that have reached replicative senescence are
more resistant to dying and occur more in aging
bodies.
Senescent fibroblasts may cause cancer by secreting
enzymes that degrade the extra-cellular matrix*,
researchers believe this leads to cancer.
*Extra-cellular matrix: underlying structure created by
fibroblasts, controls the growth of other cells.
Genes and Longevity
Telomeres:
Protects the genetic encoding from becoming a short
sequence during replication.
Tail at the end of every chromosome that gets shorter
as the cell divides.
In theory, when telomeres become too short their
function is disrupted and the cell stops dividing.
Telomerase:
Enzyme responsible for restoring lost telomeric
sequences in cells. As a result cells can divide
indefinitely.
Mostly found in sperm and egg cells.
Telomerase enzyme is also activated in cancer cells.
Telomeres
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Telomeres Biochemistry and Aging
Oxygen Radicals:
Oxygen radicals is one of the leading causes of
aging.
Mitochondria converts oxygen to ATP, the byproducts
of the reaction are oxygen free radicals, which cause
a large amounts of damage to cells and tissues.
Reactive oxygen species/Oxygen free radicals react
readily with other molecules, called oxidation, this
process creates chain reactions within the body.
Some of the chain reactions due to oxidation are
beneficial. Example: Immune system uses free
radicals to destroy bacteria and pathogens.
Detrimental results of oxidation include: extensive
damage of membranes, proteins, and DNA.
Mitochondria are prone to free radical damage.
Oxygen Free Radicals Biochemistry and Aging
Antioxidants:
Counteract formation of free radicals
Examples: Vitamin C and E, Super-oxide Dismutase
(SOD), Catalase, Glutathione peroxidase.
Biochemistry and Aging
Protein Crosslinking:
Glucose molecules attach to proteins creating a chain
reaction in which proteins bind with other proteins the
result is a dysfunctional protein that disrupts cellular
function.
Glycation/Non-enzymatic Glycosylation is the name
of this process.
Investigators believe glycation and oxidation are
ineterdependent processes since free radicals and
cross-links seem to accelerate the formation of one
another.
Biochemistry and Aging
Advanced Glycation End products
(AGEs):
Stiffen tissues and may cause deterioration related to
aging.
Example: Collagen is the protein that forms
connective tissue, which provides structure and
support for organs and bones. When collagen reacts
with glucose the flexibility of the protein is lowered.
Lower flexibility causes organs containing this protein
to stiffen and become less efficient.
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Biochemistry and Aging
Macrophages:
Combat glycation.
Macrophages detect AGEs, engulf them and once
broken down the AGEs are dumped into the blood
stream. The bloodstream takes the residue to the
kidneys where the AGEs are filtered out and
eliminated.
Similar to antioxidants, this system is not perfect and
AGEs overcome our only defenses against them with
age. Researchers say that the efficiency of the
kidneys decreases with age and macrophages
become less active while the level of AGEs increase.
Macrophages
Macrophages (pink and purple) attacking bacteria
(green and yellow). The red circle in the picture on
the right is a red blood cell.
Biochemistry and Aging
DNA Repair and Synthesis:
It has been discovered that DNA repair mechanisms
decline with increasing age.
Organisms with better DNA repair mechanisms live
longer.
Scientists suspect that a special type of DNA only
found in the mitochondria gets damaged faster than
the DNA in the nucleus causing the energy producing
capabilities of the mitochondria to decline with age,
this decline leads to age relate diseases.
Werners Syndrome (WS), is a genetic disease that
accelerates aging and as a result people at a young
chronological age develop characteristics seen in old
people.
Werners Syndrome
A WS patient at age 14 (left); the same WS
patient at age 48 (right).
Neurodegenerative Disease
Alzheimers Decease (AD):
Progressive brain disease.
Characterized by impairment of memory and a
disturbance in at least one other thinking function (for
example, language or perception of reality).
Believed to be caused by the production and
accumulation of the beta-amyloid protein, which
leads to nerve cell death.
Loss of nerve cells lead to deficits in
neurotransmitters.
Biochemistry and Aging
Heat Shock Proteins (HSPs):
Produced when a cell is exposed to a stress.
Levels of production vary with age.
Old animals produce a low number of HSPs
compared to younger animals when they are
exposed to the same stress.
HSPs help the cell dismantle and dispose of
damaged proteins.
Facilitate the making and transport of new proteins.
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Biochemistry and Aging
Hormones:
Made in specialized group of cells called glands.
Hormones are chemicals in the body that regulate,
stimulate, and control the function of various tissues
and organs.
Aging affects the production of certain hormones, like
estrogen and testosterone.
Dehydroepiandrosterone (DHEA) and melatonin are
other hormones that decrease with age.
It is unclear what effect on the body does the
decreasing number of hormones have.
Hormones
Biochemistry and Aging
Growth Factors:
Hormones that stimulate cell activity, and in turn
affect function of tissues.
For example, the insulin-like growth factor (IGF-I)
mediates the actions of the hGH hormone.
Physiologic Clues
Rates of Aging:
Aging is different from person to person.
Within the same individual, organs and tissues age
differently.
Physiologic Clues
Normal Aging:
Heart:
Heart tissue thickens with age.
Maximal oxygen consumption decreases by 10% in
men and 7.5% in women.
This decline in oxygen consumption occurs because
the hearts pumping rate and the bodys oxygen
extraction capability decreases with time.
Arteries:
Arteries stiffen with age.
Moving the blood through the inelastic arteries
requires the heart to pump blood with more force.
Physiologic Clues
Normal Aging:
Lungs:
Maximum breathing declines 40% between ages of
20 and 70.
Brain:
Age decreases the number of axons that connect
neurons, as a result neurons dont function properly,
but their numbers dont decline.
Kidneys:
Kidneys remove less waste from the blood when they
are older.
Bladder:
Bladder capacity declines.
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Physiologic Clues
Normal Aging:
Body Fat:
Old age decreases weight by decreasing muscle
tissue and body fat.
Redistribution of body fat also occurs, body fat
redistribution is different in women and men thats
why women are less susceptible to certain conditions
including heart disease.
Bones:
Bone mineral is always lost and replaced in the body.
Around age 35, the loss becomes grater than the
replacement.
The loss is even greater in women at menopause.
Physiologic Clues
Normal Aging:
Sight:
Around age 40, focusing close up may become
difficult.
Around 70 years of age, the ability to distinguish fine
details begins to decline.
Starting at 50, there is more susceptibility to glare,
difficulty seeing at low illumination levels and more
difficulty detecting objects in motion.
Hearing:
Listening to higher frequencies becomes difficult with
age.
Hearing declines faster in men than in women.
Physiologic Clues
The Immune System:
The immune system consists of the thymus, spleen,
tonsils, bone marrow, and the lymphatic system.
Lymphocytes are of special interest when studying
aging.
B-cells and T-cells are the two classes of
lymphocytes found on the body.
B-cells grow in the bone marrow and one of their
functions is secreting antibodies when they detect the
presence of infectious agents or antigens.
Physiologic Clues
The Immune System:
T-cells are produced by the thymus, which decreases
in size as we age.
T-cells are divided into cytotoxic and helper T-cells.
Cytotoxic T-cells attack infected cells directly.
Helper T-cells produce lymphokines, chemicals that
mobilize other substances in the immune system and
cell.
T-cells that work properly tend to decrease in aging,
even though the population of T-cells remains
constant.
The Immune System