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Longevity Genes

Growing evidence suggests that subtle variations in gene codes can have significant effects on longevity. Several of these genes were found to play key roles in metabolism as well as maintenance and repair mechanisms within cells. They, therefore, attempt to minimize the accumulation of age-related damage within the organism. The process of aging is therefore under moderate genetic control which influences the rate at which damaged molecules accumulate. Through identifying the genes and pathways involved in metabolism and repair mechanisms, targets for the preservation of health and longevity can be defined.

Although the exact mechanisms leading to cellular aging remain unclear, two probable theories have been put forward. The free radical theory of aging 1 purports that aging is mainly caused by oxidative stress that develops as a result of the failure of antioxidant mechanisms to counteract harmful oxidant accumulation. The programmed theory of aging states that longevity is largely determined by the genetic make-up of an individual 2. Years of evidence suggest that the process of aging is likely a combination of both of these theories.



Glutathione is a key antioxidant molecule that functions to neutralize harmful compounds such as free radicals, peroxides, lipid peroxides, and heavy metals. Its protective role is noteworthy since it has been suggested that the enhancement of glutathione production can promote longevity and delay aging 3.

Research has shown that the main genes encoding the enzymes responsible for glutathione synthesis are prone to single nucleotide polymorphisms (SNPs) that can affect the functioning of these genes 4. Specifically, it was observed that these SNPs reduce the function of the enzymes, thereby limiting glutathione production and lowering the cell’s antioxidant defense mechanisms.

Interestingly, deficiencies in the enzymes that facilitate the antioxidant function of glutathione have also been linked to diseased states. Mostly associated with brain tissue, these deficiencies manifest as mild cognitive impairment and Alzheimer’s disease 5.

Superoxide dismutase

Superoxide dismutase is another antioxidant that contributes to neutralizing oxidants within the cell, however, it specifically ensures that the energy-producing structures remain unaffected. SNPs in this gene have been linked to the development of diabetes6, age-related cataract development6, and Alzheimer’s disease 7.

Antioxidant accessory molecules

Multiple molecules within cells play roles to support antioxidant production and function by either sensing changes in oxidant levels or facilitate the production of important antioxidant enzymes.

Oxidative stress sensing molecules

These molecules sense changes in the oxidant status of the cell, in other words, if the level of harmful oxidants reaches above a certain level, these molecules become activated and regenerate membrane-bound coenzyme Q, which is a potent antioxidant 8. Evidence has implicated SNPs in this sensing molecule to cause a significant increase in its expression in the brain, leading to an imbalance in the antioxidant/oxidant balance that is associated with Alzheimer’s disease.

Cofactor molecules for major cellular antioxidant enzymes

Cofactor molecules play indispensable roles in facilitating the production of antioxidant enzymes. Research has found that by slightly overexpressing one of these molecules, better protection from aging-associated functional decline, as well as an extended lifespan was observed in mice 9. Deficiencies in this molecule caused by SNPs have significant effects on aging, with an additional association with hearing loss being observed 10.

Telomere shortening

Telomeres are the caps at the end of each strand of DNA and their function is to protect the chromosome from damage. Each time a cell divides, these telomeres become shorter, which with time, completely prevents the cell from dividing. The shortening of telomeres is significantly associated with aging and is a central topic for anti-aging therapies. In some cases, for example, SNPs present in genes that regulate telomere length, shortening may be accelerated.

Telomerase is an enzyme that counteracts the shortening of telomeres over time. Interestingly, telomerase is almost totally absent in adult tissues which causes the telomeres of replicating cells to shorten progressively over time, leading to aging and age-associated diseases. SNPs in crucial components of the telomerase gene not only accelerate aging but have been associated with the development of several cancers 11,12 and neurological disorders 13.


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