Genomics Holy Grail: The Secret to Super-Longevity Lies in your Genes…

aging_regenerative_medicine_genetics_genome_longevity

The search for the Holy Grail in aging has long been a focus in regenerative medicine, which poses the question: why do some of us age better than others?

Now growing evidence in Genomic Studies shows that there are key genetic players in the Aging game…

genes_genome_aging_longevityEver since the Human Genome Project, which began 25 years ago, the tools available to researchers have transformed our understanding of population genetics and the complex nuances which lie within our own individual genomes.

In a recent paper published in PLOS Genetics, teams from several European research centres have revealed there is indeed a tangible molecular mechanism behind the complex phenotype of ‘super longevity’ (long-life). And this has been roughly linked to certain single-nucleotide polymorphisms (SNPs – simple mutations in the code) at particular genetic locii…

aging_longevity_einstein_ny_genes_genomics_study

There is also ongoing genetic research into ‘Super Agers’ / centenarians at the Albert Einstein College of Medicine in New York (US) (Source: AECM)

In the study led by Stuart Kim at Stanford University (US), researchers looked to pool data from the other research centres also studying aging, to expand the sample group size (800 people over 100 and about 5000 over 90). This meant a large enough sample size was able to identify several key genes as a link to the ‘longevity phenotype’.

Such Genome-Wide Association studies (GWAS) also offer an unbiased means to understand the genetic basis of  certain traits…


The New England Centenarian Study (NECS) led by Boston University identified 4 key genetic influences in Long-life:

1. ABO Locus

Controls blood type. The study results showed that centenarians are more likely to have the O blood group than controls. People with blood type O have been reported to be protected from coronary heart disease, cancer, and have lower cholesterol levels.

aging_genome_longevity_blood_type_ABO_genes

(Source: Wikipedia Commons)

2. CDKN2B/ANRIL

Implicated in the regulation of the cell life cycle, SNPs from this region have previously been found to be associated with a surprising diversity of age-related diseases. These include cardiovascular disease, type 2 diabetes, intracranial aneurisms, amyotrophic lateral sclerosis (ALS) and several cancers in the case of Anril (through a study at the Paris Descartes University).

For cardiovascular disease, this locus shows the strongest association of any locus in the genome, with each copy of the risk allele increasing one’s risk of disease by 20–30%.

3. APOE/TOMM40

APOE was initially investigated because its ɛ4 allele was known to increase the risk of Alzheimer’s and coronary artery disease, and in the study the disease-allele was shown to be depleted in long-lived populations.

There was also a relationship between the locus and incidence of age-related macular degeneration (vision loss) and total cholesterol levels.

4. SH2B3/ATXN2

Variation in this locus has been associated with a wide variety of diseases, including rheumatoid arthritis, type 2 diabetes, coronary artery disease, blood pressure and cholesterol levels.

iGWAS analysis also showed a protective SNP against lung and pancreatic cancers and promoting good bone mineral density. SH2B3 specifically encodes a signaling protein, and loss-of-function mutations in the invertebrate equivalent gene (Lnk) in fruit flies (Drosophila) was also shown to result in an extended lifespan.

drosophila_aging_melanogastar_alzheimers_longevity_genes_genome

A ortholog (equivalent gene copy) in Drosophila melanogastar (Common fruit fly) for the SH2B3 gene also seems to prolong lifespan… (Source: Wikipedia Commons)


Generally though, the study showed that one of the genetic mechanisms for extreme longevity involves the avoidance of certain risk alleles that predisposes carriers to common diseases, including coronary artery disease, Alzheimer’s, high cholesterol and chronic kidney pathologies.

Timothy Cash of the Spanish National Cancer Research Centre in Madrid went on to explain that although no concrete evidence for predicting who will live to 100 has been pinned down, these findings still represent huge progress in the field of Aging.

It’s the first time someone has shown that particular disease [variants] are depleted in centenarian populations

However, the barrier to such GWAS studies for Longevity is that centenarians are obviously quite rare, and in the US only account for around 17 per 100,000 in the population (never mind those that reach 110+!).

Nonetheless, as medical and wellness continues to improve across the world, the numbers of such super-agers is also swelling to heights we’ve never seen before. Therefore studies of the mechanisms behind aging could go on to reveal great therapeutic angles of attack for chronic diseases, which plague the aging population.

Dani Bancroft

Dani Bancroft

Editor. Originally from London and studied for a BSc (Hons) Zoology from the University of Reading, UK. Previous work includes having written for The Spark University Newspaper and the Wellcome Trust.

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4 Comments

  1. Brad Arnold
    04/01/2016 at 22:54 — Reply

    While I am not advocating solely lifestyle changes to increase longevity, it appears from this quote that they are more powerful than previously thought. Since I am 55 years old, I am on the cusp of when extreme longevity treatments will emerge, so am trying desperately to achieve escape velocity. Might I add that now we can take this genetic knowledge and alter adults genomes using gene therapy (the first commercial longevity gene therapy will be offered by BioViva very soon in their clinics in Mexico and Columbia).

    “The guru and leader and physician founder of this anti-aging revolution and great healthcare specialty, Dr. Ron Klatz, MD, DO was asked about the benefits to those communities around the world who are adopting the anti-aging lifestyle.
    He stated, that those communities all over the world are enjoying a life expectancy of 91.5 years average versus the standard 68-year life expectancy for those only receiving standard care. This is a 23.5-year difference….hence the coined term, “the anti-aging dividend.”” -David A. Kekich, Maximum Life Foundation, Longevity Press Release, Dec 31, 2015

    • Dani Bancroft
      07/01/2016 at 10:09 — Reply

      Thank you, Brad for your insightful comment. I had a look at BioViva’s site – very interesting.

  2. Steve
    13/01/2016 at 03:18 — Reply

    As a follow up, Liz Parrish, who’s the CEO of Bioviva, has become one of the first to receive a treatment targeting two gene locii in each of her cells (or, of course, as many as can be accessed via the CRISPR delivery vehicle she used) on Sept 15, 2015. One targeted a gene controlling telomere length. No confirmation yet from ongoing testing she receives on weather or not this actually “took hold” in her genome. But it is hopeful that there will be more mavericks like herself who are willing to risk their own health in the hope of saving, well, literally billions of people from the disease of aging.

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