Scientists Examining DNA of Centenarians

[DoggerDan]

http://news.yahoo.com/longevitys-secrets-sought-dna-100-olds-203909753.html

Apparently, there's something good in their genes! "By the time you reach, say, 105, "it's very hard to get there without some genetic advantages," says Dr. Thomas Perls, a geriatrics expert at Boston University."

We've been hearing about gene therapy for years, but what's the likelihood of devising a therapy to correct our deficient DNA, repairing it with theirs, so that we can live longer lives?

 

[Ryan_m_b]

To be honest this is mainly for show in my opinion. We finished the human genome project a decade ago and in decades hence we will still be deciphering the data. And that's before we start talking about transcriptomics, proteomics, metabolics and the myriad of environmental factors that lead to the phenome. Out of those hundred hundred year olds it's going to be impossible to tease out any genetic vs environmental link.

Another problem is that there is not going to be some magic longevity gene. Their phenotype is not only complex interplay between their genes and environment but also between their all of their genes. How would you know which complement of genes was responsible? Without creating thousands of knock-out variants and watching them grow for a century.

 

[Ygggdrasil]

The scientists about whom the Yahoo article reports previously published a paper in Science detailing some of the findings of their sequencing project. They claimed to find certain gene variants that seemed to appear more frequently in the centenarians than in the control population. However, other genetics researchers quickly noted some flaws in the study's design and further experiments showed that the paper's findings were just an artifact: the gene chips used to study the control population have slightly different biases and sensitivities than the gene chips used to study the centenarian population. Thus, the paper was subsequently retracted in July of this year.

This case is a cautionary tale of just how difficult it is to tease out very weak correlations from a very messy data set. Given the complex interactions between genes and environment, designing a study with the statistical power to find such correlations is extremely difficult.

 

[Greg Bernhardt]

Another problem is that there is not going to be some magic longevity gene. Their phenotype is not only complex interplay between their genes and environment but also between their all of their genes. How would you know which complement of genes was responsible? Without creating thousands of knock-out variants and watching them grow for a century.

Just started reading the book https://www.amazon.com/dp/0316017922/?tag=pfamazon01-20 in Pennsylvania. Apparently the community was studied by scientists because the residents were living very long and healthy lives. The scientists studied all aspect including genetic advantages. They couldn't find anything different. They concluded it was the communities close Italian culture which led to long life.

 

[DoggerDan]

Thanks for the responses!

Another problem is that there is not going to be some magic longevity gene. Their phenotype is not only complex interplay between their genes and environment but also between their all of their genes. How would you know which complement of genes was responsible? Without creating thousands of knock-out variants and watching them grow for a century.

Alternatively, starting with two large groups, those who are otherwise healthy yet die of old age less than 70 yrs old, and every centenarian one can get to donate some DNA. No need to track everyone and determine the differences over 100 years.

However, as you said, the complexity of interactions between myriads of genes would probably require very large sample populations to resolve any clear results.

 

[Ryan_m_b]

Just started reading the book https://www.amazon.com/dp/0316017922/?tag=pfamazon01-20 in Pennsylvania. Apparently the community was studied by scientists because the residents were living very long and healthy lives. The scientists studied all aspect including genetic advantages. They couldn't find anything different. They concluded it was the communities close Italian culture which led to long life.

Interesting, I wonder why they came to that conclusion. It's a fantastically hard thing to do, it makes me laugh to read old science fiction from the 80s and 90s where they made the mistake of assuming that once we've cracked the genome we've cracked the phenome. The reality is we're barely any closer to the latter!

Thanks for the responses!

Alternatively, starting with two large groups, those who are otherwise healthy yet die of old age less than 70 yrs old, and every centenarian one can get to donate some DNA. No need to track everyone and determine the differences over 100 years.

However, as you said, the complexity of interactions between myriads of genes would probably require very large sample populations to resolve any clear results.

It would still be extremely hard. The problem is ironically a lack of data combined with too much data. In other words even if even with thousands of people with detailed medical and personal histories as well as full genome data for all we are still missing huge swathes of their life that may be important (that's not to suggest that there's some fountain of youth that half of them live next to, just that the variables and combinations are gargantuan). On the other hand all the data we do have is a mountain to get through; I can't remember who said it but there's a quote about the results of the human genome project that goes something like "After ten years we have an ocean of data and a puddle of knowledge".

That's not to say there isn't hope. We are getting closer to understanding how phenotypes are developed and with regards to ageing the field of metabolomics (the study of all the molecules and pathways occurring within a cell/organism) holds great promise for the future.

 

[Monique]

That's why scientists turn to much simpler organisms such as C. elegans to study longevity. We know too little about the subject (although I would say big progress has been made in recent years), controlling the genetic background and environmental factors is extremely important in order to elucidate the different factors.

 

[atyy]

Interesting, I wonder why they came to that conclusion. It's a fantastically hard thing to do, it makes me laugh to read old science fiction from the 80s and 90s where they made the mistake of assuming that once we've cracked the genome we've cracked the phenome.

What is the "phenome"?

What, btw, is the human "genome" anyway? Naively, I'd expect it to include the distribution of polymorphisms in the human population, which I don't think the orginally advertised "complete genome" had.

 

[Ryan_m_b]

What is the "phenome"?

What, btw, is the human "genome" anyway? Naively, I'd expect it to include the distribution of polymorphisms in the human population, which I don't think the orginally advertised "complete genome" had.

The phenome is the sum total of physical traits that an organism expresses. It is created by the interaction between biology and the environment (in such a vague, tangled way that it's almost impossible to tease out totally).

I've heard them used interchangeably but the genome is the sum total of an organism's DNA (or RNA depending on what they are), when applied to a species it is the sum total of genes, promoters etc of that species. A genotype is the specific variation of a genome that an individual has. e.g.

Genome of Species X

Genes: A, B, C, D, E, F, G

Genotype of Species X Specimen Y

Genes: A1, B1, C2+C1, E3, F0, G1+G4

 

[atyy]

The phenome is the sum total of physical traits that an organism expresses. It is created by the interaction between biology and the environment (in such a vague, tangled way that it's almost impossible to tease out totally).

After seeing "phenome" in your post, I looked it up, and to my horror, it is quite a mainstream term nowadays! I'm the sort of old fogey who can't come to terms with "metabolome", "lipidome", "connectome" ... I only accept "genome", having been brainwashed when I was young enough to think it a word:) I can kinda live with "proteome".

 

[Ryan_m_b]

After seeing "phenome" in your post, I looked it up, and to my horror, it is quite a mainstream term nowadays! I'm the sort of old fogey who can't come to terms with "metabolome", "lipidome", "connectome" ... I only accept "genome", having been brainwashed when I was young enough to think it a word:) I can kinda live with "proteome".

I like it. Biology is a complex thing requiring a holistic approach. Breaking it down into different systems is a good way to go

 

[ViewsofMars]

I hope to return later to this topic of discussion but first off wanted to share with everyone the Glossary of Genetic Terms from the National Gnome Research Institute. I think it is a very valuable resource. Here are three terms by the NGRI:

DNA (Deoxyribonucleic Acid)
DNA is the chemical name for the molecule that carries genetic instructions in all living things. The DNA molecule consists of two strands that wind around one another to form a shape known as a double helix. Each strand has a backbone made of alternating sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of four bases--adenine (A), cytosine (C), guanine (G), and thymine (T). The two strands are held together by bonds between the bases; adenine bonds with thymine, and cytosine bonds with guanine. The sequence of the bases along the backbones serves as instructions for assembling protein and RNA molecules.

Narration Transcription
DNA, or deoxyribonucleic acid, is the central information storage system of most animals and plants, and even some viruses. The name comes from its structure, which is a sugar and phosphate backbone which have bases sticking out from it--so-called bases. So that "deoxyribo" refers to the sugar and the nucleic acid refers to the phosphate and the bases. The bases go by the names of adenine, cytosine, thymine, and guanine, otherwise known as A, C, T, and G. DNA is a remarkably simple structure. It's a polymer of four bases--A, C, T, and G--but it allows enormous complexity to be encoded by the pattern of those bases, one after another. DNA is organized structurally into chromosomes and then wound around nucleosomes as part of those chromosomes. Functionally, it's organized into genes, of which are pieces of DNA, which lead to observable traits. And those traits come not from the DNA itself, but actually from the RNA that is made from the DNA, or most commonly of proteins that are made from the RNA which is made from the DNA. So the central dogma, so-called of molecular biology, is that genes, which are made of DNA, are made into messenger RNAs, which are then made into proteins. But for the most part, the observable traits of eye color or height or one thing or another of individuals come from individual proteins.
Sometimes, we're learning in the last few years, actually, they come from RNAs themselves without being made into proteins--things like micro RNAs. But those still are relatively the exception for accounting for traits.
http://www.genome.gov/Glossary/index.cfm?id=48&textonly=true
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Genome
The genome is the entire set of genetic instructions found in a cell. In humans, the genome consists of 23 pairs of chromosomes, found in the nucleus, as well as a small chromosome found in the cells' mitochondria. These chromosomes, taken together, contain approximately 3.1 billion bases of DNA sequence.

Narration Transcription
" Genome " is a funny word. Nobody can figure out how to pronounce it. Is it "jeh-NOHM" or "JEE-nohm"? I've heard various opportunities for mispronunciations, some of which are pretty funny. But basically, it is the entire instruction set of an organism; all of the DNA. For humans, that amounts to about 3.1 billion letters of the code--As, Cs, Gs, and Ts--all in the right order, spread across all of those chromosomes.
http://www.genome.gov/Glossary/index.cfm?id=90&textonly=true
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Phenotype
A phenotype is an individual's observable traits, such as height, eye color, and blood type. The genetic contribution to the phenotype is called the genotype. Some traits are largely determined by the genotype, while other traits are largely determined by environmental factors.

Narration Transcription
"Phenotype" simply refers to an observable trait. "Pheno" simply means "observe" and comes from the same root as the word "phenomenon". And so it's an observable type of an organism, and it can refer to anything from a common trait, such as height or hair color, to presence or absence of a disease. Frequently, phenotypes are related and used--the term is used--to relate a difference in DNA sequence among individuals with a difference in trait, be it height or hair color, or disease, or what have you. But it's important to remember that phenotypes are equally, or even sometimes more greatly influenced by environmental effects than genetic effects. So a phenotype can be directly related to a genotype, but not necessarily. There's usually not a one-to-one correlation between a genotype and a phenotype. There are almost always environmental influences, such as what one eats, how much one exercises, how much one smokes, etc. All of those are environmental influences which will affect the phenotype as well.
http://www.genome.gov/Glossary/index.cfm?id=152&textonly=true