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People who have long-lived parents and grandparents often believe they will live exceptionally long too due to inherited longevity.  And now there is evidence for that, but not from the classic inheritability we were likely taught in college biology class.

This report deals with two biological terms: genotypes and phenotypes.  The genotype is the genetic makeup of an individual and is usually used to explain a particular trait.  When that particular trait is expressed or materializes, then that is known as the phenotype.

What we inherit are two sets of genetic information.  The first are the better-known inherited traits that emanate from sequences of what are called nucleotides (adenine, guanine, cytosine, thymine amino acids) on the DNA ladder.  An example of a phenotype is hair color or blood type.

We may not only inherit traits but certain disorders and syndromes.

For example, a genetic disorder that emanates from a third copy of chromosome 21 (normally there are only two copies) may result in delays in physical growth, characteristic flat facial features and stunted mental capacity – what is known as Down Syndrome.  (A chromosome is a coiled strand of DNA comprised of many genes.)  [Wikipedia, Down Syndrome]

Examples of inherited diseases

There are other examples of inherited disorders.  For instance, we may inherit one of the many storage disorders that emanate from mutations that result in enzyme deficiencies.

There are different types of mutations [see examples at Genetics Home Reference, NIH] Some of these gene mutations may result in enzyme deficiencies.

For example, an inherited single enzyme deficiency may result in inability to properly metabolize and dispose of cholesterol – a disease called Niemann-Pick disease.  [National Institutes of Health] Or a single enzyme deficiency may result in the inability to dispose of cellular debris in night vision cells of the eye (the rods) which leads to night blindness (retinitis pigmentosa).  [Wikipedia, Retinitis Pigmentosa]

Another example is an inherited syndrome called progeria where children excrete in their urine more hyaluronic acid, a gel-like water-holding molecule in connective tissue (gooey stuff that occupies space between cells).

Children with progeria develop premature baldness, cataracts, stiff joints and wrinkled skin and have a life expectancy of about 13 years.  Progeria is an inherited syndrome that emanates from a mutation in a single gene known as lamin A.  Parents and siblings of children with progeria are never affected by the disease however.  [Learning About Progeria, National Human Genome Research Institute]  So a genetic mutation can shorten the human lifespan.

Inherited disease versus age-related disease

Only about 2% of all disease emanates from gene mutations.  [KnowledgeofHealth.com April 25, 2014]  Most chronic disease is associated with aging—maladies such as diabetes, heart disease and cancer. [The Journals Of Gerontology: Series A: Biological Sciences & Medical Sciences June 2014] Hold this fact in your mind for a moment and we will return to it below.

Epigenetics: the modifiable aspect of our genes

The second type of biological inheritance emanates from the dynamic protein-making function of our genes – what is called epigenetics.  Epigenetics is when there is a change in phenotype but not genotype.  [WhatIsEpigenetics.com]

In epigenetics there are no mutations in the rungs (nucleotides) on the DNA ladder but a change in the set of instructions that are molecularly stamped into genetic memory for genes to produce or not produce proteins – what is called gene expression or silencing – in a process called epigenetic imprinting.

Epigenetic instructions are erased, reset and imprinted at the earliest stage of development, when the egg and sperm unite, and may not only include instructions inherited from either parent but also from the environment.  This opens the door to environmental and nutritional factors resetting the inherited epigenetic code.

The good news is that the resetting of the epigenetic code may also be accomplished throughout life, not just in the earliest stage of development. [Seminars Nephrology July 2013

Transgenerational inheritance

The particular focus of this report is to provide evidence that not only are the 21,000 or so genes in our genome (library of genes) erased and reset from the point of our earliest development in a process called epigenetic imprinting, but that our molecularly imprinted set of instructions is passed on to future generations.

Now, let’s return to the discussion of longevity, particularly long life that is transferred to future generations.

Over 75 years ago Cornell University researcher Clive McCay demonstrated in laboratory mice that restriction of calories prolongs the maximum lifespan.  [Journal of Nutrition July 1, 1935; Journal of Nutrition July 2010]  Subsequent animal studies suggest a doubling of the disease-free years of human life by cutting food intake in half.  But the difficulties of mounting a life-long study in humans has thwarted conclusive evidence in humans.

Longevity can be passed on to the next generation

Now for a stunning modern discovery — the dramatic doubling of the maximum lifespan of life forms in the laboratory via calorie restriction has been reported to extend into the third generation of offspring!  This is called transgenerational inheritance.

Roundworms deprived of food lived longer and so did their offspring, and their offspring, and their offspring – to the third generation!  This is accomplished via a set of genetic instructions passed along by something called small RNA (ribonucleic acid).  [Cell July 17, 2014]

RNA is similar to DNA and is comprised of just one backbone of the DNA ladder with half of the step on the ladder (just one nucleotide).  When RNA is linked with an opposing rail or backbone with another nucleotide, then this becomes the coiled DNA ladder. [RNA Structure]

This writer investigated when the first description of transgenerational inheritance was published.

A paper entitled “The Inheritance Of Acquired Characteristics” published in Science magazine in 1897 referred to “epigenesisists.”  [Science April 23, 1897]  Biologists already knew there were adaptive changes in living organisms that were acquired during life and passed on to the next generation. There was lively debate over the two rival theories of heredity – inborn generational heredity and acquired adaptive changes.  Here is how it was described in 1897:

A hypothesis has been presented which seems in some degree to mediate between the two rival theories of heredity.  The point of view taken in these publications is briefly this: Assuming the operation of natural selection as currently held, and assuming also that individual organisms through adaptation acquire modifications or new characters, then the latter will exercise a directive influence on the former quite independently of any direct inheritance of acquired characters.  For organisms which survive through adaptive modification will hand on to the next generation any ‘coincident variation’ which they may chance to have.”

How come we are only learning about this now?

The answer to the above question is that Darwinian evolution got in the way.  The notion that life forms evolve due to a process called natural selection was first proposed by Charles Darwin.

What Darwin postulated (he never conducted any experiments) was that life forms prevailed that carried certain beneficial traits that promoted their survival.  Life forms that did not harbor those advantageous traits would die off (survival of the fittest).

Natural selection can be likened to the genotype – the inherited sequence of nucleotides on the DNA ladder.  From this came the prevalent explanation of the origins of man.  Biologists then proposed that unfit genes become mutated and the fit genes remain intact which leads to greater complexity and the evolution of Homo sapiens.

But Charles Darwin himself may have acknowledged the existence of another powerful biological mechanism aside from natural selection.  He called it “conditions of existence” or “struggle for existence” which is the title of the third chapter of Darwin’s Origin Of Species.

David Marsh of the McCarrison Society For Nutrition & Health in London, England, claims Darwin claimed “conditions of existence” were more powerful than “natural selection.”

Marsh points out that natural selection has weak predictive power because of its dependence upon random events.  Marsh says recent changes in human height and shape over the past century strongly point to Darwin’s “conditions of existence.”  [Nutrition & Health Jan 2012]

Enter the idea of an anti-aging pill

The expression or occurrence of variations in different life forms via environmental or nutritional factors went overlooked, that is, till now.

Though the idea of an anti-aging pill has been talked about for decades only in the past decade or so has this idea gained credence among biologists.  [Scientific American Aug 2002]

It was the French naturalist Jean-Baptiste Lamarck (1744-1829 AD) who proposed inheritance of biological traits by non-mutational changes acquired in one generation that can be transmitted to the next.  The idea that Lamarkian inheritance has something to do with aging was first posed in 1990.  [Gerontology 1990]

While it is impractical to conduct a longevity study in humans (would require 80-100 years), animals that live shorter lives can be studied epigenetically.  Laboratory mice generally live no longer than 3 years. Mice also have about the same number of genes are humans

It has been demonstrated in laboratory mice that acquired traits (phenotypes) are transmitted to most offspring.  The first epigenetic inheritance in laboratory mice was noted in 1997.  Therefore, biologists say there are transgenerational effects that are important for human health based upon epigenetic data acquired from laboratory mice.  [Current Biology April 1997]

Mice are considered a good model for the study of human aging. [Institute of Laboratory Animal Resources Journal 2011]

So it was in 2008 that researchers who study aging embarked upon a 12-week study of laboratory mice fed with three different diets: (1) a life-prolonging limited calorie diet; (2) a normal calorie diet + the red wine molecule resveratrol; and (3) a normal calorie diet + a proprietary nutraceutical (Longevinex®) comprised of resveratrol and other herbal molecules. [Experimental Gerontology Sept 2008]

The calorie-restricted diet significantly differentiated (switched genes on or off) in 198 genes.  The resveratrol + normal calorie diet altered 225 genes.  The Longevinex® matrix of natural molecules altered 1711 genes, 9-fold more than a limited calorie diet!

Moreover, if laboratory mice are fed a calorie restricted diet over the entire lifetime, 831 genes are differentiated.  This suggests it would require a full lifetime of adherence to a limited calorie diet or a resveratrol pill to achieve the full epigenetic effect.

However, Longevinex® switched 677 of those 831 genes (82%) in the same direction (on or off) as a life-extending calorie-restricted diet, and it did this in just 12 weeks, thus making Longevinex® the closest thing to a bona fide anti-aging pill on record.  This also suggests most longevity seekers who elect to use resveratrol pills will not experience a meaningful benefit in the short term.

The gratifying knowledge is if this newly published experiment with roundworms can be translated to humans, their great, great grandchildren are likely to live longer and healthier lives.

While this report gets ahead of the science and attempts to connect the scientific dots before they are confirmed, it may be many years before any of this can be confirmed in human studies, if at all.

While Longevinex® has been reported to provide health benefits to humans [Nutrients June 4, 2013; Nutrition Research Nov 2011], even a life-long study of laboratory mice costs millions of dollars, beyond the reach of any nutraceutical company.

It is the National Institute on Aging (National Institutes of Health) that is remiss in not picking up the ball and funding a longevity study among laboratory mice that compares resveratrol and a proven nutraceutical matrix like Longevinex® with a calorie-restricted diet.  ©2014 Bill Sardi, ResveratrolNews.com