Biochemistry of Aging

Presented by Shanzay Annum Malik

Aging

• Gradual change in an organism that leads to increased risk of weakness, disease, and death over the entire adult life span of any living thing.

• There is a decline in biological functions and in ability to adapt to metabolic stress.

Changes in organs include

• reduced immunity, • loss of muscle strength, • decline in memory and cognition,• loss of colour in the hair • elasticity in the skin.

Gerontology and Geriatrics

• Gerontology is concerned with the changes that occur between maturity and death along with factors that influence these changes.

• Geriatrics focuses on health care of elderly people and promote health by preventing and treating diseases and disabilities in older adults.

Factors of Aging

• mitochondrial damage• free radicals• telomeres• apoptosis and necrosis• diseases• other effects

Mitochondria: main unit of chemical power supply

• During the synthesis of macroergical bio-molecules(high energy releasing potentials e.g. ATP) free radicals are being produced as the by-product.

• Free radicals released in large quantities cause intercellular oxidative stress (e.g. oxidative damage of mitochondria)

• damaging mitochondria and cause early apoptosis

Free radical

• A molecule that contains one or more unpaired electrons &is capable of independent existence.

• Eg : Superoxide H2O2, • hydroperoxy radical (HOO+2 )• lipid peroxideradical (ROO) • Nitric oxide (NO)

Harmful effect of free radicals

• Because of their reactive nature, free radical can provoke inflammation or altered cellular function through

• Lipid peroxidation• Protein modification• DNA modification

Lipid peroxidation product:

• React with amino acid mainly CYS, HIS,LYS to modify protein structure & function.

• Can crosslink lipid in cell membrane interrupting structure & fluidity.

Protein modification

• Proteins are major targets of free radical attack because of their high abundance & responsible for most of functional processes.

• Free radical causes oxidation & modification of certain amino acid (met, cys,His,try)

• ROS may damage protein by fragmentation• net result is loss of biological activity of proteins

DNA modification :

• Free radical induced DNA damage includes

– strand break.– DNA protein crosslink.– large range of base & sugar modification.

Telomeres

• Repetitive DNA sequences at the ends of all human chromosomes

• aging cells have shorter telomeres• length differs between species• in humans 8-14kb long

• Telomeres are thought to be the "clock" that regulates how many times an individual cell can divide.

• Telomeric sequences shorten each time the DNA replicates.

• Once the telomere shrinks to a certain level, the cell can no longer divide. Its metabolism slows down, it ages, and dies

Apoptosis and Necrosis

• There are two ways that a cell can die: • Necrosis occurs when a cell is damaged

by an external force, such as poison, a bodily injury, an infection or getting cut off from the blood supply (which might occur during a heart attack or stroke). When cells die from necrosis, it's a rather messy affair. The death causes inflammation that can cause further distress or injury within the body.

• Apoptosis or programmed cell death• When a cell is compelled to commit

suicide proteins called caspases go into action.

• They break down the cellular components needed for survival,

• production of enzymes known as DNases, which destroy the DNA in the nucleus of the cell.

Diseases

• Progeria • Werner Syndrome

other effects

• Stress Effects • Octopus Suicide : The octopus suicide

mechanism involves behaviors where Females stop eating and die of starvation

Anti-aging Agents.

• Aspirin • Caloric restriction • Exercise• laughing out louder• Resveratrol, a constituent of red wine and

grape skins has been found to extend life span

Non aging species

• Rougheye Rockfish 205 Years• Lake Sturgeon 152 Years• Aldabra Tortise 152 Years• Koi 226 Years• Bowhead Whale 211 Years