By Gene Bruno, MS, MHS
-Dean of Academics, Huntington College of Health Sciences
Depending upon the source, the life expectancy of Americans is 78.2 or 78.3 years.[i] [ii]
Why is this? That is, why do we age at the rate that we do?
There are various theories about this.
In fact, there are currently ten primary theories on aging which may be classified under the general headings of programmed aging or unprogrammed aging.
This article will provide an overview of key aging theories and their impact on life span, as well as dietary supplements that may help mitigate the impact and help promote a healthy life span.
Programmed and unprogrammed aging
To a large extent, the term ‘programmed aging’ may be described as aging resulting from genetically programmed factors.
According to Spence[iii], a strong argument can be made for some manner of programmed aging since aging begins at birth and each species seem to have its own average lifespan.
The theories contributing to the premise of programmed aging include programmed cell death, telomere theory, gene theory, and gene mutation theory.
‘Unprogrammed aging’ may be described as aging resulting from molecular damage to normal body cells and molecules.
The theories contributing to the premise of unprogrammed aging include cross-linkage theory, free radical theory, stress protein theory, cellular garbage or accumulated waste theory, wear and tear theory, and autoimmune theory.
In programmed aging, the telomere theory is gaining ground.
The same may be said of the free radical theory with regard to unprogrammed aging, particularly in consideration of free radical damage to DNA.
Telomeres
As cells age, they lose a certain number of base pairs of DNA, known as telomeres, from the end of each chromosome every time cell division takes place. This is a result of the fact that DNA polymerase, which builds corresponding DNA strands, cannot start the synthesis of the new strand, but must wait for primase to do the job. As a result, the telomere section of the chromosome cannot be reproduced.
Although the telomeres are ‘sacrificial’ DNA without any necessary information content, there is still a problem.
When these telomeres have decreased to a critical length, cell division ceases; although cell senescence (aging) may continue for a time.[iv]
This finite ability to replicate is known as the ‘Hayflick limit’, and has been seen in cultured normal human and animal cells.[v] Fibroblast cells taken from adults would only divide about 20 times in vitro, although this limit is rarely, if ever, reached in the body.[vi]
Here is a more simplistic way to explain this phenomenon: At the ends of our chromosomes are stretches of DNA called telomeres. These telomeres protect our genetic data, making it possible for cells to divide.
Telomeres have been compared with the plastic tips on shoelaces because they prevent chromosome ends from fraying and sticking to each other, which would scramble our genetic information.
Yet, each time a cell divides, the telomeres get shorter. When they get too short, the cell no longer can divide and becomes inactive or “senescent” or dies. This process is associated with aging.[vii]
Free radicals and DNA
Spence[viii] describes free radicals as molecules with unpaired electrons, formed as a result of normal interaction with oxygen. Free radicals react chemically with other molecules, causing damage.
The free radical theory of aging describes free radical damage to macromolecules such as lipids, proteins and DNA, which in turn, may initiate changes explaining the various unprogrammed theories of aging.
Furthermore, the free radical theory of aging maintains that oxidative stress and reactive oxygen species damage the structure of the genome.[ix]
Consequently, damage to DNA can accumulate as chemically “silent” errors in repair—insertions, deletions, substitutions, transpositions, and inversions in DNA sequences—that affect the expression and structure of proteins.[x]
Dietary supplement intervention
Telomerase is an enzyme that adds telomere to DNA. Certain nutraceuticals and nutraceutical combinations have been shown to promote telomerase activity and help increase telomere length.
Likewise, research also indicates that certain nutraceuticals may help enhance DNA repair and reduce DNA damage.
Green Tea
In a sample of 976 Chinese men aged 65 years and over, telomere length (TL) was measured and daily intake of food groups was assessed. An analysis was undertaken to examine the association between food group intake and TL.
The results were that Chinese tea consumption was significantly associated with TL after adjustment for demographics and lifestyle factors (P = 0.002). Mean difference in TL for those in the highest quartile of Chinese tea consumption (>3 cups/d or >750 ml/d) as compared with those in the lowest quartile of Chinese tea consumption ( <or= 0.28 cups/d or <or= 70 ml/d) was 0.46 kb, corresponding to approximately a difference of 5 years of life.
In conclusion, Chinese tea consumption was positively associated with TL in elderly Chinese men.[xi]
Astragalus membranaceus
This study[xii] assessed the effects of these two compounds, extracted from Astragalus membranaceus, on telomere shortening rate and DNA repair ability in 2BS cells.
The telomere shortening rates of the cells cultured with HDTIC-1 or HDTIC-2 were 31.5 and 41.1 bp with each division, respectively, which were much less than that of the control cells (71.1 bp/PD).
We also found that 2BS cells pretreated with HDTIC-1 or HDTIC-2 had a significant reduction in DNA damage after exposure to 200 microM H(2)O(2) for 5 min. Moreover, the 100 microM H(2)O(2)-induced DNA damage was significantly repaired after the damaged cells were continually cultured with HDTIC for 1 h.
These results suggest that HDTIC compounds slow down the telomere shortening rate of 2BS cells, which is mainly due to the biological properties of the compounds including the reduction of DNA damage and the improvement of DNA repair ability.
In addition, the slowdown of telomere shortening rate, the reduction of DNA damage, and the improvement of DNA repair ability induced by HDTIC may be responsible for their delay of replicative senescence.
Vitamin D
The objective of this study[xiii] was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer Leukocyte telomere length (LTL).
Serum vitamin D concentrations were measured in 2160 women, aged 18-79 y (mean age: 49.4), from a large population-based cohort of twins. The results were that serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003).
The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging.
Resveratrol
Resveratrol is a natural substance found in many plants, including grapes, peanuts[xiv] and Japanese Knotweed (Polygonum cuspidatum).[xv]
Resveratrol’s introduction into the dietary supplement market a few years back was based upon the consideration that intake of it and other polyphenol compounds from red wine may contribute to the “French paradox”; the unexpectedly low rate of death from cardiovascular disease in the Mediterranean population, despite a diet that is relatively high in saturated fat.[xvi]
In-vitro studies suggest that resveratrol is capable of promoting telomerase activity, thereby helping to maintain telomere length.
This has been shown to the case without affecting cell proliferation.[xvii]
Likewise, resveratrol has also demonstrated an ability to delay cell senescence (aging) by its action on telemorase.[xviii]
In addition, research has shown that resveratrol significantly extends the lifespan of lower organisms such as the yeast Saccharomyces cerevisiae[xix], the worm Caenorhabditis elegans, and the fruit fly Drosophila melanogaster.[xx]
Other research demonstrated that resveratrol had similar life extension effects on the short-lived fish, Nothobranchius furzeri,[xxi] also increasing swimming performance, and cognitive performance.
Another study has shown that resveratrol improved the health and survival of mice that were on a high-calorie diet.[xxii]
Grape seed polyphenols
A study[xxiii] set out to determine (a); whether DNA damage is elevated in mice that carry mutations that predispose them to Alzheimer’s disease (AD) relative to control mice, and (b); whether increasing the intake of dietary polyphenols from grape seed extract could reduce genomic instability.
DNA damage was measured using the micronucleus (MN) assay in both buccal mucosa and erythrocytes and an absolute telomere length assay for both buccal mucosa and olfactory bulb tissue. The results were a significant 7-fold decrease in buccal MN frequency (p=0.01) for AD mice fed diets containing grape seed.
Similarly, in polychromatic erythrocytes, a non-significant reduction of 34.8% in MN frequency was found for the grape side extract group respectively compared to the AD Control. A non-significant 2-fold increase in buccal cell telomere length was also evident for the grape seed extract group compared to the AD control group.
Chlorella
Oxidative agents can cause damage to cellular DNA, included telomere length.
In a study[xxiv] where cells were exposed to the oxidative effects of hydrogen peroxide, telomere length decreased significantly coupled with a concomitant decline of telomerase activity. However, these decreases were prevented with prior and post treatment of Chlorella vulgaris to those cells.
Consequently, Chlorella as found to be an effective preventive against telemorase-shortening due to oxidative damage.
Vitamin E, vitamin A, folate, preformed niacin and calcium
Results from a recent population study[xxv] suggest that key micronutrients affect genome stability in human subjects in vivo. The results have recently been reported of a cytogenetic epidemiological study of 190 healthy individuals, (mean age 47.8 years, 46% males), designed to determine the association between dietary intake, measured using an FFQ, and genome damage in lymphocytes(33), measured using the cytokinesis-block micronucleus assay.
Multivariate analysis of baseline data shows that the highest tertile of intake of vitamin E, vitamin A, folate, preformed niacin (niacin or niacinamide) and calcium is associated with significant reductions in micronucleus frequency, (a robust biomarker of chromosome breakage or loss).
Multivitamins
In a cross-sectional analysis of data from 586 early participants (age 35–74 y) published in the American Journal of Clinical Nutrition, [xxvi] multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire. Relative telomere length of leukocyte DNA was also measured.
The results were that after age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres.
Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend = 0.002).
This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women.
Cat’s claw
A proprietary water/dialysis extract of cat’s claw standardized to 8% carboxyl alkyl esters (CAE) is of significant interest, since it has been shown to be capable of enhancing DNA repair.
In animal research, this action was observed in the repair of DNA single strand breaks (SSB) and double strand breaks (DSB) after whole body irradiation.[xxvii] Likewise, human research groups ingesting varying doses of CAE (250 mg/day and 350 mg/day) experienced significantly enhanced DNA repair and reduced DNA damage compared to non-supplemented groups after induction of DNA damage by a standard dose of hydrogen peroxide.[xxviii]
Zinc
Zinc has also been shown to enhance DNA repair.[xxix]
Additionally, in a study elucidated later in this module, a combination of zinc, niacinamide and mushrooms where shown to promote DNA repair.[xxx]
As little as 10 mg was used in this research. A possible mechanism for zinc’s effects was seen in an in-vitro study on rat cell line where low intracellular zinc resulting from nutritional deficiencies induced oxidative DNA damage, and disrupted p53, NF-κB and AP-1 DNA binding that in turn affect DNA repair.[xxxi]
Niacinamide
Likewise, niacinamide is a direct metabolic nutritional precursor to the formation of cellular nicotinamide adenine dinucleotide (NAD)[xxxii], which in turn is essential to energy production and is also a co-substrate for the participation of poly (ADP-ribose) polymerase (PARP) in DNA repair.[xxxiii] [xxxiv] [xxxv]
In other words, providing increased nutritional support to enhance DNA repair is another pathway to resist DNA damage.
This pathway is independent of both direct down-regulation of free radical production by NF-κB down expression and by antioxidant free radical scavengers.
In addition, the studies including niacinamide as mentioned in the two previous paragraphs lend support to this nutrients role in promoting DNA repair. The dose used is 100 mg.
Conclusion
Telomere length and DNA damage/repair may profoundly impact life span.
The use of key dietary supplements can may help promote a healthy telomere length, promote DNA repair and reduce DNA damage.
Collectively, this may help extend life span.
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