- Aging & Longevity
Theories Of Aging
The Aging Process
Universal aging refers to age changes that all people share, while probablistic aging refers to age changes that may happen in some, but not all people as they grow older.
There are two basic theories of senescence or aging, which include the following :
- Programmatic theory - It states that aging, like "development" is a pre-ordained process due to an inherent genetic program that is executed at a rate that is characteristic of each species.
- Stochastic theory - This states that random cumulative damage to genes and proteins due to environmental changes, such as pollution, toxins etc ultimately produces aging.
Telomeres Are The Terminal Portions Of Chromosomes
The Programmatic Theory
This theory is based on the following factors :
- Telomere shortening - Telomeres are the terminal portions of our chromosomes that consist of many hundreds of base pairs (or genetic units). During each cell division, the final base pairs or ends of each chromosome cannot be replicated, resulting in progressive shortening with each round of cell division. A special reverse transcriptase, telomerase enzyme can replicate these chromosomal ends but this enzyme is normally expressed in germ-line cells (the cells concerned with reproduction). Thus telomere length shortens more than 30% during the lifespan of a normal person. Telomeres of individuals with premature aging syndromes, such as Werner's syndrome and Progeria, are much more shorter than those of normal individuals. These short telomeres signal apoptosis or programmed cell decay, and compromise the DNA stability, contributing to aging.
- Cellular senescence or reduced regeneration - The limitation of capacity of cells to undergo multiplication is termed as cellular senescence. The aged or senescent cells display critically short telomeres and irreversible growth arrest. Thus with increased age, the damaged cells cannot be replaced by new, more efficiently functioning cells, leading to reduced efficiency of overall functioning of our body. Though all body cells do not undergo replication( as it is believed that the neurons or nerve cells either do not multiply or replicate at an extremely slow rate), this aspect takes into account organ systems with fast regenerative capacity, such as the liver, and skin.
Caloric Restriction Reduces Oxidation Stress And Expand the Life span
The Stochastic Theory
Various components of stochastic theory of aging include the following :
- Oxidative Stress and Caloric Restriction - Oxygen which is the basic requirement for our survival, readily accepts single-electron transfers during various metabolic reactions, generating O-2, H2O2, and OH free radicals, that further generate an array of Reactive Oxygen Species (ROS) which cause severe damage. The end result being peroxidation of membrane fatty acids, DNA damage (base alterations, single stranded breaks) and loss of sulphydryl groups of proteins, leading to inactivation of enzymes and increased protein breakdown. If the antioxidative defense systems of an individual are not fully efficient, then throughout life the cells accumulate molecular damage. There is an age associated increase in both reactive oxygen species generation and the level of oxidatively damaged proteins and DNA. Restriction of calories which in turn decreases the metabolic rate, reduces oxidative stress and expands the lifespan. Lifelong caloric restriction is also associated with delays in age associated disorders manifested as an improvement in learning ability, immune responses, gene expression, enzyme activities, hormonal action, glucose utilization, DNA repair, and rate of protein synthesis.
- Aging and DNA damage - Presence of longevity genes - Certain changes in our DNA known as mutations, occur throughout the life of an individual. Reduced DNA repair capacity, along with cumulative DNA damage, plays a major role in the aging process. In certain other species, the so called longevity genes have been identified, whose mutation or over expression increases lifespan. All characterized longevity genes encode proteins that assist in control of environmental stress. The ras-2 gene in yeast, whose over expression delays senescence, acts as an environmental sensor for response to a variety of stressors , including starvation,ultra violet irradiation, oxidative damage, and heat shock.
- Amino acid racemization - This is a process that changes the orientation of the three dimensional structure of amino acids, the building blocks of proteins. It substitutes Dextro amino acids for Levo-amino acids within proteins with increasing age, and leads to reduced protein function. It causes accumulation of non-functional proteins in the aged.
- Non-enzymatic glycosylation - This is a complex metabolic process that occurs when sugars condense with protein amino groups, resulting in brown discoloration of tissue, loss of function, and increased degradation. When this process occurs in collagen protein of skin, it leads to cross linking and increased degradation, consequently increasing the appearance of wrinkles.
Aging and the Immune System
Our immune system has two main functions that include-
- To defend our body against external insults.
- Internal immunological surveillance.
Age associated decrements in the function of B- and T- lymphocytes (the WBC) and a variety of other accessory cells, are postulated to contribute to the increased incidence of infections and malignancies in the elderly.
Both genetic make up and environmental damage are responsible for aging
Aging in humans refers to a multi dimensional process of physical, psychological, and social changes.
Aging and longevity are determined by a complex mixture of environmental and genetic factors. Dietary factors, especially caloric restriction (intake of 60-70% of normal requirement) can substantially delay or prevent many age related diseases