# Which mutations cause aging

Could somebody, possibly, provide a list of the mutations that cause aging- the specific mutations- "hotspots" and/or discuss that with me (ie you could pm me) thanks

## Answers and Replies

Monique
Staff Emeritus
Gold Member
A problem comes with making a definition for aging. In order to find mutations you must first have a clear phenotype to look for, something that you can measure. Aging is not something you can measure, but you can look at extremes such as Progeroid syndromes, which are commonly regarded as accelerated aging. Studying such syndromes might give us insight into an aspect of aging, but you must understand that it is not representative for aging in the general population.

Hutchinson–Gilford progeria syndrome is caused by de novo mutations in Lamin A (LMNA), a nuclear protein. Werner progeria syndrome is caused by mutations in the WRN gene. You can find more information on PubMed.

just to verify:

you would not be able to use gene therapy in one or more organs to make it so that the mutations did not contribute to aging (until of course they accumulated again) because of gene and/or genome lengthening, even if you could do that just by repairing the repair system and/or other things?

(Obviously theres maybe other reasons than gene/genome lengthening for why you maybe couldnt do that)

this post is only regarding normal etc aging; not things like accelerated aging/anything like that

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I'm still not sure what your question is. If you're looking for information on chromosome shortening, which eventually leads to its destruction, look up telomeres. http://en.wikipedia.org/wiki/Telomere

well like my friend said okay, you could repair/replace all the mutations that contribute to aging with gene therapy, but that would end up with the- he said gene or genome- being lengthened too much and so he said it wouldnt work for that reason if nothing else.is that correct? also, you cant prevent all mutations that contribute to aging with telomere maintenance and/or other things, correct? and you cant repair and/or replace etc all the mutations that contribute to aging with anything other than gene therapy right?

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Monique
Staff Emeritus
Gold Member
A large component of aging is wear-and-tear due to environmental factors, not genetic factors.

If you were going to repair certain adverse mutations with gene therapy, then doing it by homologous recombination would not lengthen the genome. Thinking that gene therapy will cure aging is too speculative.

Here's an article from Albert Einstein College of Medicine of Yeshiva University, New York City that I think relates to this discussion. It's important to me to know where the money is going for research.
NIH Awards Einstein Researcher $11.2 Million to Study Genome Instability as a Cause of Aging August 27, 2009— (BRONX, NY) — The National Institutes of Health (NIH) has awarded Albert Einstein College of Medicine of Yeshiva University a five-year,$11.2 million grant to study the impact of damage to DNA on aging and disease. Research funded by this grant, and conducted by a consortium of scientists, could reveal the role of genome maintenance systems in delaying aging and will begin to explore novel interventions to maintain health in old age.

Led by Jan Vijg, Ph.D., chairman of genetics at Einstein, the research project will build on the consortium's previous, internationally recognized work involving mice that undergo accelerated aging. This research has shown that interfering with the cellular processes responsible for DNA repair leads to what appears to be premature aging in these animals. These results indicate that accumulating DNA errors may underpin the aging process.

The investigators in the consortium now plan to see if treatments based on these results can extend life spans of mice bred to have short lives. "We can try to use interventions that are based on alleviating DNA damage," Dr. Vijg says. "One approach, for example, could be the use of antioxidants, which neutralize free radicals, the chemicals that contribute to DNA damage."

Altogether, the research project involves four main areas of study:

■unraveling the mechanisms that lead from DNA damage to premature as well as normal aging
■testing the role of DNA maintenance and repair as a pro-longevity system in humans
■developing sets of blood-based biomarkers that indicate premature aging in mouse models, and validate these biomarkers in normally aging mice and in humans
■developing new, experimental interventions that neutralize symptoms of premature aging in the short-lived mice

The NIH program project grant has funded five groups of scientists who are working on interrelated parts of the project's four research areas. In addition to Dr. Vijg's group, another Einstein team is headed by Yousin Suh, Ph.D., associate professor of medicine, and of genetics. Yousin Suh, Ph.D.Dr. Suh will take advantage of a unique Einstein resource: tissue samples from Ashkenazi Jewish centenarians — living to age 100 and beyond. Using this relatively homogeneous population, brought together by her Einstein collaborator, Nir Barzilai, M.D., Dr. Suh will look for gene variations that are associated with longevity. Her team will test these
"longevity genes" by inserting them into otherwise ordinary human cells and then observing whether the inserted genes improve cellular function.

The other groups of investigators are affiliated with: the Buck Institute for Age Research in Novato, CA, studying the genetic causes of cell senescence (led by Dr. Judy Campisi); the Erasmus University Medical Center in Rotterdam, the Netherlands, developing biomarkers and studying interventions in DNA repair-defective mouse models (led by Dr. Jan Hoeijmakers); and the University of Texas Health Science Center in San Antonio, TX, also working with DNA repair-defective mouse models (led by Dr. Paul Hasty). Finally, the National Institute of Public Health and the Environment, in Bilthoven, the Netherlands, harbors the central core facility with all the mouse models kept under standardized, germ-free conditions (led by Dr. Harry van Steeg).

The information developed by the Einstein project may help to unravel one of the major mechanisms through which we age, which in turn may lead to new approaches to intervene on a rational basis. "Ultimately," says Dr. Vijg, "our hope is that this research will lead to new strategies that can be deployed for delaying, preventing, or even curing age-related disease."
###
http://www.einstein.yu.edu/home/news.asp?id=401

I'm on a roll so to speak. Here's another article from Albert Einstein College of Medicine of Yeshiva University, New York City

NIH Awards Einstein $3.5 Million To Study Epigenomics Of Human Health And Disease September 17, 2009 — (Bronx, NY) — The National Institutes of Health (NIH) has awarded Albert Einstein College of Medicine of Yeshiva University two grants totaling$3.5 million to study epigenetic changes — chemical modifications of genes caused by stress, diet or other environmental influences — and how they contribute to human diseases and biological processes.

The NIH will award approximately \$62 million to medical institutions over the next five years to study the impact of epigenetic changes on a number of diseases and conditions, including tumor development, hardening of the arteries, autism, glaucoma, asthma, aging, and abnormal growth and development. The grants will build on the work of the NIH Roadmap for Medical Research's Epigenomics Program.

Einstein's grants will focus on epigenetic modifications related to abnormal fetal growth and to chronic kidney disease, led, respectively, by Francine H. Einstein, M.D., assistant professor of obstetrics & gynecology and women's health and Katalin Susztak M.D., Ph.D., associate professor of medicine. Their research will illuminate the total repertoire of epigenetic influences — referred to as the "epigenome"— that characterize each of these conditions.

"The goal of epigenomics research is in part to understand how human diseases are caused and how environmental factors affect them," says John M. Greally, M.B., B.Ch., Ph.D., associate professor of genetics and of medicine at Einstein, who directs Einstein's Center for Epigenomics. "This research is also driven by the fact that epigenetic processes are inherently reversible and could therefore respond to therapies that reverse long-term damage to the cells. These pioneering studies by Drs. Einstein and Susztak are the first steps towards this ultimate goal."

"Epigenomics represents the next phase in our understanding of genetic regulation of health and disease," says NIH Director Francis Collins, M.D., Ph.D. "These awards will address the extent to which diet and environmental exposures produce long-lasting effects through changes in DNA regulation." Dr. Collins notes that the initiative "is expected to profoundly alter the way we understand, diagnose and treat disease."

The main epigenetic modification being studied in these projects is DNA methylation, the addition of methyl groups to the cytosine bases of DNA, often associated with silencing of nearby genes. DNA methylation is one of a number of epigenetic regulatory mechanisms that control gene expression in normal cells but can become altered in disease. For example, epigenetic changes have been found in every type of cancer that researchers have studied.

[snip]

http://www.einstein.yu.edu/home/news.asp?id=416

I like what Dr. John M. Greally and Dr. Francis Collins said.

These are relevant.

Scaffidi P, Misteli T. Lamin A-dependent nuclear defects in human aging. Science. 2006 May 19;312(5776):1059-63. Epub 2006 Apr 27.

Scaffidi P, Misteli T. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med. 2005 Apr;11(4):440-5. Epub 2005 Mar 6.

okay well if in theory you could replace mutations using homologous recombination gene therapy...would it be possible for someone to pm me or post a list of all known mutations that definitely contribute to aging?

Monique
Staff Emeritus
Gold Member
You have not defined aging, so no: nobody can give you the mutations. And again, a large part of aging is environmental factors.

For instance: what mutations causes an empty can of soda to age? Clearly it has no mutations, it is corroding by chemical actions.

well I understand that theres other potential causes of aging than mutations
I guess by aging I mean= what leads to death..organ failure..etc..I suppose I need to be more specific...so I wanted a list of all the mutations that contribute to this so I can see what mutated genes would need to be replaced via homologous recombination recombination to make it so that, those genes were not mutated (under they became mutated again of course). if some mutations cant be put on a list because theyd be specific to an individual I understand. But Id really like a list or talk to someone about getting a list maybe someone could pm or something, Id be willing to pay for a list
I realize defining aging and not being able to measure it etc make it more complex. I guess I should come up with a better definition for aging then "the changes that come with time that kill you" for the purpose of this thread I mean give me some time and I'll try to come up with a better definition of aging for the purposes of this thread but you sort of get the jist of what I mean when I say aging right; wrinkles death etc

but like I..would like to know about getting a list of the known mutations that contribute to aging (I know not every mutation will be included on there) I realize I need to define aging first for the purposes of this thread..but you sort of get the jist of what I mean by aging right...please, any help is appreciated; thanks

also I understand there are causes of aging other than mutations; if so perhaps give a list? If you define aging as accumulating injuries you could maybe repair the body with stem cells etc so...Im not referring to injuries as a cause of aging (in this thread) what environmental causes of aging are you referring to. I know mutations for sure cause aging dont know the other causes also Im only referring to biological human tissue aging

i know there may be/is other reasons for aging Im just trying to find out about mutations if anyone could help like a lot or a little or something they could also pm me their email address etc or just pm me

thanks

Monique
Staff Emeritus
Gold Member
In the second post you mention you are only interested in normal aging and not accelerated aging syndromes. I guess the best general hallmark of 'healthy aging' is longevity, you may be interested in studying the journal of Biogerontology. There have been recent advances where by mutating certain genes scientists were able to increase the longevity of the nematode C. elegans, you might want to look into that as well.

There still is the problem that there may be alleles or mutations that dispose you to age faster than someone else (as in the case of accelerated aging syndromes), but there is also the situation where the process of aging introduced mutations in the genome (this would fit the description of injuries, the process is random and different for each cell in your body). From your description it is not clear which of the two you are talking about.

I realize that there may be mutations in an individual which may allow them to age faster/may be different from mutations in other individuals..I just want a list of the mutations that definitely contribute t aging in all individuals or @ least most individuals; u could always check to see if a person didnt have the mutation I guess yes I need to read the different journals etc if anyone can help me get the lists faster please let me know

if youre aware of any other causes of aging please list them

what I want to do is take a cell and compare it to a template/human genome to see the mutations let me know if someone cna help me with that

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Monique
Staff Emeritus