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Longevity's Relationship to Genetic Signals & Antioxidants

By William Misner Ph.D.

The relationship between dietary antioxidants and longevity is argued vigorously and not well understood. Preventing free radical cellular damage and an inevitable premature death using antioxidants is rational. W.B. Grant's and Caldwell Esselstyn's research papers demonstrate that a plant-based antioxidant-rich diet not only prevent pathological disease but in some cases reverses pathology leading to predicted death. Longevity is effected by genetic signals that turn on longevity or conversely turn on apoptosis (cyclic cell death).

During the past two millennia average life expectancy at birth, determined by the chances for death, of humans has risen from 30 years, in ancient Rome, to almost 80 years today in the developed countries. Chances for death are now largely determined by the inherent aging process after age 28. The inherent aging process after age 28 limits life expectancy from birth to around 85 years, but the maximum life span to about 122 years. Modern man has improved survival from birth to age 28 above that of his pre-iron age relatives.

LONGEVITY, as a property of being long-lived, has natural limitations with a strong GENETIC COMPONENT, apparent from research from yeast to humans. Genetic screening efforts with invertebrates have unraveled multiple genetic pathways that imply longevity is promoted through the manipulation of metabolism and the resistance to OXIDATIVE STRESS. Antioxidants versus free radicals may influence the primary "intrinsic" aging process as well as several secondary age-associated pathological processes. C. elegans and D. melanogaster are important systems for studying aging. This is especially true for the former, in which the age-1 mutant has been shown to greatly increase the life span over the wild-type strain. This genetic mutation results due to increased antioxidative enzyme activities, namely Cu-Zn superoxide dismutase and catalase. Therefore the genomic and free radical theories are very closely linked. Down's syndrome (trisomy 21) is characterized by a significantly shortened life span and also plagued by increased oxidative stress, which results in various free radical-related disturbances. Exactly how this extra chromosome results in an increased production of reactive oxygen species is only partially understood. Not only are several major age-associated diseases clearly affected by increased oxidative stress (atherosclerosis, cancer, parkinson's, multiple sclerosis), but the fact that there are numerous natural protective mechanisms to prevent oxyradical-induced cellular damage speaks loudly that this theory has a key role in aging [the presence of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, among others; various important intrinsic (uric acid, bilirubin, -SH proteins, glutathione, etc.) and extrinsic (vitamins C, E, carotenoids, flavonoids, etc.) antioxidants; and metal chelating proteins to prevent Fenton and Haber-Weiss chemistry]. A major part of the free radical theory involves the damaging role of reactive oxygen species and various toxins on mitochondria. These lead to numerous mitochondrial DNA mutations which result in a progressive reduction in energy output, significantly below that needed in body tissues. This can result in various signs of aging, such as loss of memory, hearing, vision, and stamina. OXIDATIVE STRESS also inactivates critical enzymes and other proteins. Oxidative stress is implicated in a wide variety of degenerative processes, diseases and syndromes, including the following: mutagenesis, cell transformation and cancer; atherosclerosis, arteriosclerosis, heart attacks, strokes and ischaemia/reperfusion injury; chronic inflammatory diseases, such as rheumatoid arthritis, lupus erythematosus and psoriatic arthritis; acute inflammatory problems, such as wound healing; photo-oxidative stresses to the eye, such as cataract; central-nervous-system disorders, such as certain forms of familial amyotrophic lateral sclerosis, certain glutathione peroxidase-linked adolescent seizures, Parkinson's disease and Alzheimer's dementia; and a wide variety of age-related disorders, perhaps even including factors underlying the aging process itself. The beneficial impact of exogenous antioxidants reduces age-related degenerative diseases that may forecast an improvement in life span and enhance quality of life. Reducing free radical damage may reduce vulnerability to pathological disease during "Golden Years." In other words, antioxidants reduce pathology disease's premature mortality toll.

There is a decrease in specific microntrients that occur in tandem with increased age. They are: L-carnitine, acetyl-l-carnitine (ALC), creatine phosphate, phenylalanine, s-adenosylmethionine (SAMe), chondroitin sulfate (CSA-B form), ratio of chondroitin sulfate-A (CSA-A) to chondroitin sulfate-C (CSA-C), hyaluronic acid, lutein, stomach hydrochloric acid, cytochrome c oxidase, delta-6 desaturase, glutathione peroxidase, superoxide dismutase (SOD), melatonin, adenosine triphosphate (ATP), docosahexaenoic acid (DHA), phosphatidylcholine, phosphatidylserine (PS), beneficial bacteria (probiotics), bromine, calcium, chromium, copper, iron, magnesium, acetylcholine, nitric oxide, ribonucleic acid (RNA), carnosine, coenzyme CO-Q10, methylsulfonylmethane (MSM), choline, folic acid, lipoic acid, vitamin B1, vitamin C, vitamin B6, vitamin B12, vitamin D, and gamma-tocopherol.

There are also an associated decreases in endogenous substances that occur in tandem with increased age. They are: Na-PCA, elastin, norepinephrine, insulin-like growth factor-1 (IGF-1), nerve growth factor (NGF), androstenediol, androstenedione, DHEA (dehydroepiandrosterone), follicle stimulating hormone (FSH), human growth hormone (hGH), luteinizing hormone (LH), pregnenolone, relaxin, testosterone, thymic hormones, thymosin, plasma thymulin, thyroid hormones, and dopamine. .

Consumption of micronutrient antioxidants through food or supplementation reduce free radical oxidation damages to the cells resulting in inhibition of the cell's vulnerability to pathological disease. Several other endogenous substances also decrease with age may have a gene component or a genetic signaling property. This second group of substances may be influenced by diet and supplements. It is proposed that micronutrients and other endogenous substances could be factors in raising the current life expectancy from 85 to the maximum life span to about 122 years. How to reduce free radical damage to cells is currently better understood than how to design dietary protocols that turn off longevity-inhibitor genes or turn on longevity-enhancing genes. .

Hayflick lists the causes of age change:

"Unlike aging, there is no disease or pathology that shares these six qualities":
(a) Occur in every multicellular animal that reaches a fixed size at reproductive maturity
(b) Cross virtually all species barriers
(c) Occur in all members of a species only after the age of reproductive maturation
(d) Occur in all animals removed from the wild and protected by humans even when that species probably has not experienced aging for thousands or even millions of years
(e) Occur in virtually all animate and inanimate matter
(f) Have the same universal molecular etiology, that is, thermodynamic instability

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