CELLULAR AGING

Galen (A.D. 129 –c. 199)

-Thought that aging was due to changes in body humors that began in early life

-These changes caused a slow increase in dryness and coldness of the body

Roger Bacon (c. 1220-1292)

- One of the first to suggest a “wear and tear” theory

- Aging is the result of abuses and insults to the body system

- Good hygiene might slow the aging process

Charles Darwin (1809-1892)

- Attributed aging to the loss of irritability in the nervous and muscular tissue

Theories of Aging have been around for more than

2000 years

 Aging is, at least in part, the result of accumulating damage to molecules in our body—such as:Proteins lipids, and nucleic acids (DNA and RNA)

It turns out that damage can come from many different sources, both internal and external.

Where does the damage come from?

Cellular Aging

Even though, understanding cellular aging is at the heart of a great deal of research, there remain many unanswered questions about how aging happens at the cellular level

There are three major theories of cellular agingFree radical theory agingTelomere and aging DNA repair defects

CELLULAR AGING

• The free radical theory of aging argues that oxidative damage accumulates with age and drives the aging process

• Free radicals form from environmental factors such as X-rays, strenuous exercise, sunlight, pollution

• alcohol and smoking

Free Radical Theory of Aging

Example of ROS

• Mitochondria need oxygen to generate cellular energy, and humans need a constant supply of that energy to survive

• But oxygen has a darker side, and it has attracted the attention of scientists who study aging

• Because forms of oxygen itself are free radicals, very breathing and our otherwise healthy aerobic exercise generate free radicals that help along the aging process

O2, the good, the bad and the ugly

Free radicals can damage many kinds of biological molecules by stealing their electrons, the attacked molecule also becomes a free radical and this lead to a chain reaction

These renegade oxygen-containing species can mutate your genes, damage the lipids that make up your cellular membranes, and break the proteins that do much of the cell's work, thereby causing cellular injury in multiple and overlapping ways

The thieving oxygen

 

ROS or reactive oxygen species can be formed by different processes including normal cell metabolic processes.

• Scientists have already uncovered clear links between reactive oxygen compounds and aging

• Fruit flies genetically engineered to produce high levels of enzymes that destroy reactive oxygen species lived almost 50 percent longer than normal flies

• The same enzymes also made the microscopic roundworm Caenorhabditis elegans live significantly longer than normal

Free radicals Cell damage aging

• Substances that prevent the harmful effects of oxidation are known as antioxidants. Natural antioxidants include vitamin C, vitamin E and beta carotene, the substance that our body uses to produce vitamin A.

• Enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase can neutralize free radicals

• These antioxidant and enzymes that trap free radicals may slow or reverse the oxidation of proteins during aging

• At the ends of each chromosome is a long non-functional strand of DNA called a telomere. Telomeres consist of the six-base repeating sequence TTAGGG

• With each cell division, some of the telomere is lost, (it is analogous to a photocopier cutting off the first and last lines of each page)

• Once a cell's telomeres shrink to a critical minimum size, the cell takes notice and stops dividing.

TELOMERES AND AGING

The 46 human chromosomes are shown in blue, with the telomeres appearing as

white pinpoints.

• For humans, the length of the remaining telomere is usually an indicator of how many divisions a dividing cell has left

• The Hayflick limit (or Hayflick Phenomenon) is the number of times a normal cell population will divide before it stops, presumably because the telomere reach a critical length

• Germ cells, stem cells and "immortalized" cancer cells contain an enzyme called telomerase that replaces lost telomeres, thus preventing them from experiencing a Hayflick Limit

• Telomerase usually absent in most somatic tissues

Telomerase activity

• The DNA damage theory of aging proposes that aging is a consequence of unrepaired DNA damage accumulation

• Unless precisely repaired, nuclear DNA damage can lead to mutation and/or other deleterious cellular and organismal consequences

• An example of cellular aging that occur via DNA repair defect is Werner Syndrome

DNA repair defects

• Werner syndrome is a premature aging disease that begins in adolescence or early adulthood and results in the appearance of old age by 30-40 years of age

• Its physical characteristics may include short stature (common from childhood on) and other features usually developing during adulthood: wrinkled skin, baldness, cataracts, muscular atrophy and a tendency to diabetes mellitus, among others

Aging in Fast-Forward: Werner Syndrome

• Mutations in the WRN gene cause Werner syndrome. The WRN gene provides instructions for producing the Werner protein, which is thought to perform several tasks related to the maintenance and repair of DNA

• The disorder is inherited and transmitted as an autosomal recessive trait. Cells from WS patients have a shorter lifespan in culture than do normal cells

• Werner syndrome is estimated to affect 1 in 200,000 individuals in the United States. This syndrome occurs more often in Japan, affecting 1 in 20,000 to 1 in 40,000 people

•Perhaps, the combination of the three theories (free radicals, telomeres and DNA repair defect) contribute to the process of cellular aging

•Research is still going on as it has been going on for over 2000 years to understand the complex process of cellular aging

CONCLUSION