Comprehensive Library Of Resveratrol News

Longevity seekers often pay too much attention to lengthening telomeres, those end caps on our chromosomes, or even activation of known longevity genes such as the sirtuin1 survival gene.  The question remains: precisely what causes humans to get old and why does the rate of aging differ from individual to individual?  What influences genes to accelerate or slow the rate of aging?  The same library of ~20,000 genes is housed inside the billions of cells in every human body.  What causes one person’s set of genes to age them faster than another individual?

Inborn errors (mutations) in the sequence of rungs on the DNA ladder called nucleotides, which are responsible for only ~2% of human disease, explain the rare occurrence of premature aging syndromes such as progeria where young children exhibit premature baldness, cataracts and skin aging. [Age and Ageing 1998]  Progeria emanates from a mutation in a single gene called lamin A.

The rest of humanity ages normally but unevenly.  Some die of old age after six or seven decades and others succumb after ten or even twelve decades.  What explains the widely differing rate of aging and why do some people look old sooner than others?

While the study of human aging is largely focused on what happens inside living cells, in progeria it is the non-cellular gooey stuff in between cells called connective tissue that ages.  DNA cannot directly explain the wrinkled skin, hair loss and cloudy cataracts characteristic of progeria children.  There is no DNA in connective tissue.

If humans have young functioning cells in their brain, eyes, heart, liver and other organs but their connective tissue ages prematurely they will end up looking old and dying young like progeria children.  Few if any anti-aging strategies address connective tissue aging.  Who wants to live long and look old, wrinkled and decrepit?

Photos of Jean Calment, the longest-living human (lived 122 years), at age 80 (she looked 40) and at age 120 years.

While most people believe they will live long because they inherited longevity from family members or fear they won’t live very long because their forefathers died in their 40s and 50s, inherited gene structure (mutations) may have little to do with this.  It turns out, for most humans, our lives shape our genes rather than genes shape our lives.

By the way, this latter group, comprised of people whose forefathers died young, generally comprises most longevity seekers – they fear dying young like their fathers and mothers did.

These two sister mice are genetically identical and came from the same litter. The brown mouse is inherently lean and will live longer.

In recent times it has been discovered that genes have a dynamic property.  Genes produce proteins in response to environmental factors (radiation, temperature, oxygen, food or lack of food).  This environmental-responsive protein-making property of genes is called epigenetics.

The genes that were actively producing proteins (called gene expression) or weren’t producing proteins (called gene silencing) in your very early development in the womb are “imprinted” to form a semi-permanent inherited (but reversible) gene profile.  It is this epigenetic profile that is passed on to future generations much as gene mutations are.

This biological phenomenon of gene imprinting has recently been demonstrated in a community in northern Sweden in the 1800s when the supply of food suddenly and temporarily became plentiful due to weather changes and its residents over-ate and their descendants died prematurely.  There was a trans-generational (inherited) effect.

A wonderful YouTube presentation that explains why “DNA is not your destiny” can be viewed to better understand gene imprinting.  [YouTube]

The network of genes that control aging have always been there.  What causes these genes to begin making proteins and accelerate aging?  What causes humans to lose the strength and resilience of youth?

From Iron To Rust In Seven Decades

The primary malignant factors of aging are accumulated metals – primarily iron and copper.  While iron is an essential nutrient transported on the back of the iron-binding red hemoglobin pigment in red blood cells, when unbound iron can generate inflammation that destroys tissues and induces DNA mutations.

During youth humans need all the iron they can get to produce millions of red blood cells per second in their bone marrow.  But when physical growth slows, around the age of 18 years, the demand for iron declines and iron begins to accumulate, first in males and then later in females when menstruation ceases with the change of life.  When iron begins to accumulate is when genes begin switching from a youthful state to an aging state.

So researchers recently put the metal theory of aging to the test.  They fed laboratory mice three different diets: (1) adequate intake of iron; (2) an iron-enriched diet and (3) an iron-restricted diet.   Here is what happened to those three groups of rodents.

The major impact was that iron-restricted animals lost weight.  The leanness of youth was restored (see chart below).  [PLoS One April 12, 2013]

An Iron-Restricted Diet Restored The Leanness Of Youth

Body Weight Of Animals On Three Different Iron Diets
DIET	Normal diet	Iron restricted	Iron enriched
Total iron intake, milligrams (78 days)	64.22 mg	16.81 mg	627.64 mg
Initial body weight	526.52 grams	510.75 grams	514.62 grams
Final body weight	496.91 grams	446.28 grams	471.85 grams
Source:  Dietary iron concentration may influence aging process by altering oxidative stress in tissues of adult rats.  PLoS One April 12, 2013

The second thing researchers measured was the expression (activation) of a gene called senescence marker protein-30 (SMP30). Proteins made by this gene control cellular senescence – its gradual inability to grow and replicate itself. [Methods Molecular Biology 2007] Synthesis of SMP30 protein differed between iron-restricted and iron-fortified animals.  The less SMP30 gene protein that is produced the greater the deterioration of cellular functions with advancing age. [Mechanisms Ageing & Development March 16, 1999]

Other important genes that control iron storage (ferritin) were also modified by iron.  The main point here is that genes connected with aging and iron storage are switched on or off by a modifiable factor  — iron.  The lesson is that the dietary intake of iron and its progressive accumulation in the human body govern the genes, not the other way around.

The presumption is that the less iron consumed in adulthood the slower a living organism would age.  Superlongevity, living 110+ years, is not achieved by calorie restriction per se but more succinctly by reduction of iron intake.  There are over one-thousand published reports on the topic of calorie restriction and aging but only eleven that deal with iron, calorie restriction and aging. [PubMed.gov]

A second lesson here is that we don’t necessarily need to deprive ourselves of food as biologists claim to approach the superlongevity achieved with calorie restriction.  Longevity is within reach of every human being.

Iron-restricted animals also exhibited much lower measures of oxidation (as measured by a noxious protein called malondialdehyde).

The study concludes that: “iron chelation (removal) therapy may be effective in treating or preventing oxidative stress and thus retard the aging process.  Both iron restriction in the diet and use of chelating agents may reduce the amount of iron and therefore minimize damage to proteins.”  [PLoS One April 12, 2013]

Another interesting correlation is made between SMP30 gene protein and diet.  Calorie-restricted animals live longer and a limited calorie diet has been shown to prevent the age-related decrease in SMP30 protein.  [Antioxidants Redox Signaling March-April 2006]  Connecting the dots, it may not be the reduction in calories but actually the reduction in iron via limited food intake that produces the anti-aging effects.

Some of these findings were reported in a study published more than two decades earlier.  That study showed that while iron storage levels (as measure by the iron-binding protein ferritin) are much higher in normally-fed animals, iron storage (ferritin) still rises dramatically with advancing age. [Age 1997]

Iron determines gender differences in the rate of aging

In another compelling study, the level of stored iron (ferritin) in human subjects aged 20-93 years showed a rise in every age group studied and ferritin levels were high in males than females, which may help explain why women generally live longer than men. [Age Ageing May 1981]

Yet another study also showed that males exhibit iron storage (ferritin) levels about four times higher than females (108 versus 26 nanograms per milliliter of blood).  Low ferritin levels were often observed in women aged 18-45 years but rarely found among women after age 50 years.  [Japanese Journal Clinical Pathology – Rinsho Byori May 1991]

Ferritin levels have been found to be 42% higher in the skin of postmenopausal women than premenopausal women. [Journal Cosmetic Science May-June 2013]

A disturbing study shows that the ferritin iron storage number in males reaches a steady state by age 30 years and doesn’t rise thereafter.  [Journal Clinical Pathology Dec 2010] This means the accumulation of iron in males may largely take place prior to men thinking they need to do something about it.

Organs especially affected by iron-induced aging

These scientific findings become relevant when correlated with the fact that high levels of stored iron (ferritin) in the blood increase the possibility for early diagnosis with Alzheimer’s memory loss.  [Frontiers Aging Neuroscience Dec 6, 2012] This again suggests iron chelation (removal) can reverse age-related damage in the human brain. [Frontiers Aging Neuroscience July 2013]

Iron may play a role in many age-related eye disorders including cataracts.  Iron chelation is suggested for prevention. [Progress Retinal Eye Research Nov 2007]

Excessive iron as exhibited by elevated ferritin levels is predictive of diabetes. [Diabetes Metabolic Research Review May 2013]

Diet-wise, the consumption of processed red meat, which provides a highly absorbable form of iron (heme iron), is associated with all-cause mortality. [American Journal Epidemiology Feb 1, 2014; Archives Internal Medicine March 23, 2009]

Of note, a limited calorie diet is associated with preservation of motor performance in lab animals which is correlated with reduce iron deposition in brain tissue.  [Journal Neuroscience Aug 22, 2012]

It is not surprising to learn that humans with genetically-induced iron overload exhibit shortened telomeres. [American Journal Hematology June 2013]

One study conducted on the island of Sardinia, a Mediterranean island known for its numbers of centenarians, reveals that centenarians exhibit a shortage of iron. [Experimental Gerontology Dec 2014]

There is little question that iron is the “malignant spirit in successful aging.”  [Ageing Research Review Jan 2003]

What to do

Longevity seekers who limit red meat in their diet and who supplement their diet with iron-controlling (chelating) molecules such as quercetin and rice bran IP6 [PLoS One July 24, 2014; Cancer Aug 1985], stand a chance of mimicking the biological effect of a calorie restricted diet known to double the healthspan and lifespan of laboratory mice.  A modest dose of these molecules minimizes the risk for anemia.

The red wine molecule resveratrol (rez-v-air-ah-trol) has been shown to increase iron storage via ferritin and thus serve as an antioxidant by virtue of reduction of available iron to induce oxidation. [Biochemistry July 30, 2013]

Of additional note, the consumption of refined sugars, in particular high fructose corn syrup, demonstrably increases iron absorption from food. [PLoS One Dec 10, 2013]

Preservation of youthful appearance + longevity

Finally, in addition to longevity, the ability to maintain a youthful-looking appearance may be achievable by supplementation with oral hyaluronic acid, a natural gel-like water-holding molecule produced in abundance in youth. Oral hyaluronic acid is a space filler and moisturizer in human skin. [Scientific World Journal 2014; Nutrition Journal July 11, 2014]

Furthermore, iron chelators also inhibit the production of the enzyme (hyaluronidase) that breaks down hyaluronic acid. [International Journal Biological Macromolecules Feb 1998]

Of additional note, oral hyaluronic acid may aid in the maintenance of a youthful-sounding voice contrasted with the typical guttural voice of old age. [Laryngoscope May 2001]

Dietary supplementation with the yellow carotenoid pigments lutein and zeaxanthin also guard against wrinkling and skin aging. [Skin Pharmacology Physiology 2007]

It may be even be possible for those children stricken with progeria, a premature aging syndrome, to benefit from these epigenetic therapies.

Resveratrol, quercetin, IP6 rice bran, hyaluronic acid and lutein/zeaxanthin are provided in a novel dietary supplement. [Longevinex Advantage]  — ©2014 Bill Sardi, ResveratrolNews.com