An insight into the theory of aging.
The deterioration of functions of the body over time is aging.
Theories of Aging
There are many theories about the mechanisms of age related changes. No one theory is sufficiently able to explain the process of aging, and they often contradict one another. All valid theories of aging must meet three broad criteria:
- The aging changes that the theory addresses must occur commonly in all members of a humans.
- The process must be progressive with time. That is, the changes that result from the proposed process must become more obvious as the person grows older.
- The process must produce changes that cause organ dysfunctions and that ultimately cause a particular body organ or system to fail.
Modern biological theories of aging in humans currently fall into two main categories: programmed and damage or error theories. The programmed theories imply that aging follows a biological timetable (regulated by changes in gene expression that affect the systems responsible for maintenance, repair and defense responses), and the damage or error theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of ageing.
These two categories of theory are also referred to as non-programmed aging theories based on evolutionary concepts (where aging is considered the result of an organism’s inability to better combat natural deteriorative processes), and programmed ageing theories (which consider aging to ultimately be the result of a biological mechanism or program that purposely causes or allows deterioration and death in order to obtain a direct evolutionary benefit achieved by limiting lifespan beyond a species-specific optimum lifespan.
The programmed theory:
- Aging by Program, where biological clocks act through hormones to control the pace of aging.
- Gene Theory, which considers aging to be the result of a sequential switching on and off of certain genes, with senescence being defined as the time when age-associated deficits are manifested.
- Autoimmune Theory, which states that the immune system is programmed to decline over time, leading to an increased vulnerability to infectious disease and thus ageing and death.
The damage or error theory:
Wear and tear theory, where vital parts in our cells and tissues wear out resulting in ageing. Rate of living theory, that supports the theory that the greater an organism’s rate of oxygen basal, metabolism, the shorter its life span Cross-linkage theory, according to which an accumulation of cross-linked proteins damages cells and tissues, slowing down bodily processes and thus result in ageing. Free radicals theory, which proposes that superoxide and other free radicals cause damage to the macromolecular components of the cell, giving rise to accumulated damage causing cells, and eventually organs, to stop
When we examine a chromosome, there are two components to note: the DNA, and the telomere. The telomere exists on the ends of the chromosome to provide structural integrity so that the DNA does not unravel. Think of telomeres like the plastic cap (aglet) on the end of a shoelace. When shoes are new, not having a cap on the end of the lace will not cause fraying, but with each wear the shoe lace is exposed to the environment, which adds up over time, leading to physical damage. Telomeres become damaged as we age because whenever the cell divides, the telomere is nicked. Therefore, with each divide the telomere gets short and shorter. Cellular division is a natural biological process, and after approximately 50 divisions, the cell reaches what is known as the “Hayflick limit” and senescence begins.
Image credit: Oumere
Telomeres are similar to the plastic caps protecting your shoelaces. When telomeres become too short, they can no longer protect DNA, and senescence occurs.
REACTIVE OXYGEN SPECIES
Studies showed that cellular senescence is commonly triggered by various forms of DNA damage. Mutant mice that are deficient in DNA repair show premature senescence and progeroid phenotypes, suggesting the involvement of DNA damage-induced senescence in aging.
Sources of DNA damage include external sources, such as ionizing radiation tobacco smoke, air pollution and genotoxic drugs, and cell-intrinsic sources, such as replication errors, programmed double-strand breaks, and DNA damaging agents—reactive oxygen species (ROS).
Image source: http://churchandstate.org.uk/2013/02/the-first-person-to-live-to-150-has-already-been-born/
Reactive oxygen species (ROS),such as superoxide anion, hydroxyl radical, hydrogen peroxide and nitric oxide, are normal byproducts of metabolism took place in mitochondria, and are believed to be one important source of DNA damage.
ROS can damage the mitochondria’s DNA (mtDNA) and proteins, and the mutant mtDNA in turn are more liable to produce ROS byproducts. Therefore a positive feedback loop of ROS is established. With age the number of mutant mtDNA increase and the mitochondrial functions decline, leading to an increased production of ROS.
The increased generation of ROS can cause lipid peroxidation, protein damage, and several types of DNA lesions in cells. Therefore, ROS are considered important factors in the mechanisms of such diseases as diabetes, cancer, atherosclerosis, heart attacks, Alzheimer’s disease, as well as in aging. Evidence has shown that species that live longer generally show higher cellular oxidative stress resistance and lower levels of mitochondrial ROS production compared to species that live shorter.
The free radical theory of human aging
Some studies have shown that calorie restriction (i.e., a 20-40% reduction of dietary caloric intake) extends life expectancy in several species ranging from yeast to rodents. One possible explanation is that caloric restriction reduced production of reactive oxygen species by mitochondria. In addition, calorie restriction induces autophagy that removes harmful proteins and organelles, thereby reducing the accumulating damage to the cell. However, this phenomenon has not yet been demonstrated in humans.
Changes in Physical Function Related to Human Aging
The rate and progression of cellular aging can vary greatly from person to person. Yet, generally, over time, aging affects the cells of every major organ of the body. The age-related physiological changes occurs all areas like on the cardiovascular, respiratory, renal/urinary, endocrine, gastrointestinal, and musculoskeletal systems, and on the skin.
The biology of aging
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Ivanova DG, Yankova TM: The free radical theory of aging in search of a strategy for increasing life span. Folia Med 2013;55(1):33-41.
Lagouge M, Larsson NG: The Role of Mitochondrial DNA Mutations and Free Radicals in Disease and Ageing. J. Intern. Med. 2013;273(6):529-543.