A number of age-related diseases have been traced to having dangerous versions (called alleles) of certain genes. Indeed, many older adults free of these diseases have been found to possess the desirable, apparently disease-protective, variants of those same genes. Thus, the same gene that in one form is a longevity assurance gene might in another form be one that decreases longevity. Some age-related diseases with origins in our genes include:

Heart disease
Cancer
Neurological disorders
Macular Degeneration
Osteoporosis

Two genes with effects on heart disease have been linked to human longevity. The most well studied of these genes, called apolipoprotein E (apoE), produces a protein that circulates in our blood. Researchers have found that those people who carry at least one copy of the E4 variant of the apoE gene have a higher risk of heart disease (and Alzheimer's disease) than those who carry at least one E2 variant. Statistically, people who survive to age 100 have been found to be about half as likely to carry the E4 gene and somewhat more likely to carry the E2.¹³ Interestingly, investigators have found that people possessing two copies of the apparently protective E2 (i.e., one from each parent) have an increased likelihood of high blood triglyceride levels, a predictor for heart disease. This would seem to negate its protective effect.¹⁴

A second gene with a known association with heart disease is the gene that produces a substance known as angiotensin converting enzyme (ACE). ACE affects blood pressure regulation. Researchers looking at this gene's effects have found a paradox: people who carry the variant of this gene that is associated with an increased risk of heart disease also have a longer life expectancy.¹⁵

Research around both the apoE and ACE genes, suggests some of the difficulty of untangling the effects of individual genes on complex disease and aging processes.

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While much cancer is caused by external factors (smoking, toxins like asbestos and radon, repeated sunburns), scientists are uncovering an important role for genetics in both susceptibility and resistance to various cancers.

Tobacco-related cancer: The apoE gene, already investigated for its role in heart disease, also seems to play a role in susceptibility to cigarette-induced cancers. For example, researchers have found that those smokers who have survived into old age without cancer have a higher frequency of the protective, E2 variant of the apoE gene.¹⁶

Breast cancer. Another gene linked to cancer susceptibility is a gene called L-myc. In a Russian study, the so-called S variant of that gene was strongly associated with the risk of breast cancer (57% of women with disease had it, compared to 41% of healthy controls).¹⁷

Gastrointestinal cancer: In animal models, susceptibility for various forms of colon cancer can be inherited. Researchers have looked at strains of mice known to develop gastrointestinal cancers similar to human cancers. Artificial insertion of a gene called Apc into these mice increases their risk of gastrointestinal cancer 40-100 times normal. Studies are underway to identify similar genes in humans.¹⁸

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Alzheimer's disease: Early onset familial Alzheimer's disease arises before age 60. Mutations in genes for proteins called presenilins are responsible for 50% of familial Alzheimer's disease. Alzheimer's disease that comes on after age 60 is associated with the same E4 variant of apolipoprotein E gene that increases the risk of heart disease.¹⁹

Stroke: Mice that inherit the undesirable E4 version of the apoE gene have an increased risk of stroke.²⁰ In other animal studies, researchers have found that genes play a role in recovery from stroke. Older rats with deliberately induced strokes have less ability to turn on the genes that could promote recovery than younger rats also induced to have strokes.²¹

Cognitive function: The gene for apoE appears to affect cognitive function among elderly people who smoke or drink. Possession of the generally less helpful E4 variant seems to decrease the risk of cognitive decline among smokers and light drinkers,²² while increasing cognitive decline among heavier drinkers.²³

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Our old friend ApoE and its E4 variant confer dangerous and protective effects on various age-related processes. For example, French studies have found that macular degeneration, the leading cause of age-related blindness, occurs less frequently among those with the E4 variant of apoE.²⁴

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In yet another example of the varied effects of apoE4, postmenopausal women who have the allele suffer twice the rate of bone density loss and osteoporosis than women without the E4 variant.²⁵ Of note, however, estrogen replacement therapy is equally effective in restoring bone mineral density in women with E4 or without it.

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