Aging The biology of senescence

Topics to cover• Aging• Types of Aging• Theories related to aging• Causes of Aging• Life span• Senescence• conclusion

Definition of some terms• Senescence – The process of aging at the cell and

organismal levels.• Gerontology – is the branch of biomedical sciences

that studies aging.• Lifespan – Longest time that species is capable of

living. (110 years for humans)

• Life expectancy – the amount of time a member of a species can except to live. (72-76 years for humans)

What is Aging?• Aging is the progressive accumulation of changes with

time , associated with or responsible for the ever increasing susceptibility to disease and death which accompanies advancing age.

• These changes create a normal physiologic decline seen in middle and late adulthood.

Changes during puberty Graying of hair

Primary aging• Physiologic changes associated with age. • Lungs & heart function decreases with age.• Cellular immune system is most affected.• Liver & kidney functions diminishes as well.• Decrease in homeostatic reserve & therefore

elderly people cannot tolerate various diseases stress.

Secondary aging• Is the increased rate of aging changes that stems

from disease & psycho-socio-economic problem.• Chronic diseases have mostly replaced acute

illness.• Diabetes, rheumatic diseases, chronic CVD smoking, poor nutrition & lack of exercise.• To some degree it is Reversible & Controllable so

prevention & early detection is of paramount importance

Senescence• The process by which a cell looses its ability to

divide, grow, and function. This loss of function ultimately ends in death.

A degenerative process, only.Has no positive features.

Symptoms of normal aging• EXTERNAL• More grey hair on your head.• Skin is not as smooth as it used to be.

Distinction between different ageing processes

1) UNIVERSAL AGEING : age changes that all people share

2) PROBABILISTIC AGEING : age changes that may happen to some , but not all people as they grow older for e.g. : onset of type II diabetes.

3) CHRONOLOGICAL AGEING : it refers to how old a person is.

4) SOCIAL AGEING : society’s expectations of how people should act as they grow older.

5) BIOLOGICAL AGEING : an organism’s physical state as it grows.

6) PROXIMAL AGEING : age-based effects that comes about because of factors in the recent past.

7) DISTAL AGEING : age-based differences that can be traced back to cause early in prison’s life.

Groups of Aging theories• There are 2 main groups of aging theories• First - aging is natural & programmed in the body,

while • second - aging is a result of damage which is accumulated over time.

• Complex interaction of genetics, chemistry, physiology & behavior.

Programmed Theories• Assert that the human body is designed to age

(biological timeline).

Programmed Senescence TheoryNeuroendocrine TheoryImmunological TheoryCellular clock theoryTelomeric Theory

Theories of Aging• Programmed longevity - caused by genes switching “on” &

“off” over time.• E.g., Hay flick's Limits Fibroblast was removed from Umbilical cord & cultured it divided & re-divided until 50 divisions after this point it cannot divide further

• Neuroendocrine theory - changes in hormones control aging.

• E.g., Menopause – there is Decreased level of estrogen & progesterone, Hot flashes & insomnia

• Immunological theory - programmed to decline over time, leaving people more susceptible to diseases.

• E.g., Decreased T cells in adults - leads to increased diseases in older adults - increased autoimmune diseases in adults

• Cellular clock theory - cells hitting their programmed reproductive limit.

Telomeric Theory • This is an extension of the “Hayflick Limit.”• Telomeres are specialized DNA sequences at

the end of chromosomes.– They shorten with each cell division.– When the telomeres become too short, the cell enters

the senescence stage.• In the normal process of DNA replication, the

end of the chromosome is not copied exactly, which leaves an un-replicated gap.

Telomeric Theory

• Shortened telomeres are found in:– Atherosclerosis – Heart disease– Hepatitis– Cirrhosis

Telomeric Theory and Cancer• 90% of cancer cells have been found to

possess telomerase.– Telomerase prevents the telomere from

shortening.– This allows the cancer cells to reproduce, resulting

in tumor growth.• Research areas

– Measuring telomerase may help detect cancer.– Stopping telomerase may fight cancer by causing

death of cancer cells.– Telomerase may be used to help with wound

healing or the immune response.

Error theories• Assert that aging is caused by environmental damage to

our body’s systems, which accumulate over time.

Wear & Tear theory Rate of living theory Cross linking theory Free radical theoryCatastrophe theorySomatic mutation theory

• Wear & tear – oldest hypothesis that cells & tissues simply wear out with time.

• E.g., wearing out of the skeletal system such as in osteoarthritis

• Rates of living – faster an organism uses oxygen, the shorter it lives.

• E.g., animals with rapid metabolism tend to have the shortest lifespan i.e., birds.

• Studies examining the relationship between metabolic rates and longevity have produced inconsistent results, limiting the usefulness of this theory.

• Cross-linking (glycation) - cross linked proteins accumulate & slow down body processes.

• E.g., non-enzymatic glycosylation reaction occur when glucose molecules attach to proteins causing a chain of chemical reactions resulting in a structural change to the proteins

- loss of flexibility of connective tissue - micro vascular changes in arteries• Genome error - genetic mutation causes cells to

malfunction

• Free radicals (oxidative stress) – cause damage to cells & eventually impairs function.

Free radical cycleThe free radical “grabs” a electron from any molecule it its vicinity.

It does this because electrons like to exist in pairs.

When it “grabs” an electron from another molecule, it damages the other molecule.

Free Radicals

As the free radical (green) attacks the membrane it can release another type free radical (blue).

Damaged membrane

The free radical (blue) attacks the DNA releasing another free radical (purple).

mitochondrion

Free Radicals

anti-oxidantmolecule

Repaired membrane damaged

DNA

The anti-oxidant molecule destroys the damaging free radical. The membrane repairs itself, but the DNA remains damaged, impairing the cells function. In addition, the anti-oxidant molecule now has an unpaired electron and thus becomes a new radical.

Free Radical Theory• Free radicals do not go unchecked. The body

has a multi-layered defense system that reacts and detoxifies the damaging radicals.

• Defenses include:– Natural antioxidants in the body, such as bilirubin.– Enzymes such as superoxide dismutase (SOD),

catalase, & glutathione peroxidase.– Dietary antioxidants such as beta carotene, and the

vitamins C and E.

Can This Stop Aging?

Somatic Mutation • Genetic mutations occur and accumulate with

age in the somatic cell causing the cell to:– Deteriorate– Malfunction

• Accumulation of mutations result in :– Damage to the DNA

The theory states that aging is an imbalance between DNA’s ability to repair itself and accumulating DNA damage.

– When the damage exceeds the repair, the cell malfunctions and this can lead to senescence.

DIVISION OF THE LIFE SPANBoth human and animal’s life is often divided into various ages

1)Juvenile[via infancy/childhood/adolescence(0-19)]2)Early adulthood(20-39)3)Middle adulthood(40-49)4)Late adulthood(60 and rest of the life)

Ages can also be divided into decades

Terms ages

1)Denarian 10-192)Vicenarian 20-29 3)Tricenarian 30-394)Quadragenarian 40-495)Quinquagenarian 50-596)Sexagenarian 60-697)Septuagenarian 70-798)Octogenarian 80-89

WHAT IS SENESCENCE?Senescence refer to state or process of ageing.

There are different types of senescence. They are1)NEGLIGIBLE SENESCENCE : Numerous species show very low sign of ageing this is known as negligible senescence for e. g fishes like lake trout and the rock fish, invertebrate like sea anemone and lobster.

2)CELLULAR SENESCENCE: In human and other animals, cellular senescence has been attributed to the shortening of telomeres with each cell cycle, when telomere become too short, the cell dies. The length of the telomeres is therefore the “molecular clock” predicted by hay flick. Telomere length is maintained in immortal cell for e.g. germ cells and keratinocytes stem cells but not other skin cell types.

CAUSES OF AGEING

Ageing can be as a result of animal’s genetic set up and can be due to environmental factors, nutritional influence, social and psychological reasons.

1)GENETIC SET UP AS A CAUSE It is found even under ideal condition an organism is destined to age and die at particular time. So far, no animal or plant is found to be immortal. The genetic setup must be influencing this phenomenon like any other psychological activity of an organism.

2)ENVIRONMENTAL INFLUENCE The surrounding in which the organism lives affect a lot by a way of pollution, stress etc.

3) INFLUENCE OF NUTRITION AND HEALTH PRACTICE ON AGEING

• Nutritional status of an animal can affect the ageing process. Lack of essential nutritional component needed for a healthy living can enhance ageing process. Irregularity of meals, lack of sleep, smoking habits, alcohol consumption, lack of exercise, tension and worries etc., cumulatively cause in enhancing ageing.

4) SOCIAL AND PSYCHOLOGICAL INFLUENCES

• Psychological factors like insecurity, stress etc. can largely affect the organisms, life span. Stress can be psychological, occupational and nutritional also.

PREVENTION AND REVERSAL•Several drugs and food supplements have been shown to retard or reverse the biological affects of ageing in animal model•Resveratrol: a chemical found in red grapes, have been shown to extend the Life span of yeast by 60%•The combination of Acetyl-L-cartinine and α-lipoic acid if been fed to rat produce a rejuvenating affect.•Rapamycin: is generally used to suppress the immune system and prevents the rejection of transplanted organs.•By using cosmetics also we can look some year younger

Can you delay or stop aging by taking vitamins and other free radical scavengers?

• There is no evidence-based proof that dietary supplements delay or stop aging. This is a big area of nutrition quackery. BEWARE!

• Remember, there is a lot of evidence-based proof that taking some supplements INCREASES cancer rate, for example lung cancer. Smokers who take beta-carotene supplements have higher lung cancer rates than smokers not taking these supplements.

• Therefore, the risk/benefit ratio is in favor of NOT taking SUPPLEMENTS to retard aging.

CONCLUSION1) Ageing is a universal truth of life on earth.2) Ageing is a process that is witnessed globally i.e.

irrespective of place in any part of the world.3) Ageing affects all individual of species.4) But recent development in science and technology

has helped to overcome Senescence to a certain extent.

The End

REFERENCES• 1) Development biology - Scott f. gilbert• 2) Development biology - Leon. W. Broader• 3) Cell biology, genetics and developmental biology - k. sharada and Mathew Joseph4) www.en.m.wikipedia.org/wiki/Ageing5) www.d.sc.discovery.com6) www.uga.edu.com