Our Genome Changes Over Lifetime, And May Explain Many 'Late-onset' Diseases

[n2doc]

ScienceDaily (June 25, 2008) — Researchers at Johns Hopkins have found that epigenetic marks on DNA-chemical marks other than the DNA sequence-do indeed change over a person's lifetime, and that the degree of change is similar among family members. The team suggests that overall genome health is heritable and that epigenetic changes occurring over one's lifetime may explain why disease susceptibility increases with age.

"We're beginning to see that epigenetics stands at the center of modern medicine because epigenetic changes, unlike DNA sequence which is the same in every cell, can occur as a result of dietary and other environmental exposure," says Andrew P. Feinberg, M.D., M.P.H, a professor of molecular biology and genetics and director of the Epigenetics Center at the Johns Hopkins School of Medicine. "Epigenetics might very well play a role in diseases like diabetes, autism and cancer."

If epigenetics does contribute to such diseases through interaction with environment or aging, says Feinberg, a person's epigenetic marks would change over time. So his team embarked on an international collaboration to see if that was true. They focused on methylation-one particular type of epigenetic mark, where chemical methyl groups are attached to DNA.

"Inappropriate methylation levels can contribute to disease-too much might turn necessary genes off, too little might turn genes on at the wrong time or in the wrong cell," says Vilmundur Gudnason, MD, PhD, professor of cardiovascular genetics at the University of Iceland director of the Icelandic Heart Association's Heart Preventive Clinic and Research Institute. "Methylation levels can vary subtly from one person to the next, so the best way to get a handle on significant changes is to study the same individuals over time."

more:
http://www.sciencedaily.com/releases/2008/06/080624174849.htm

[Trajan]

1. It has been my layman's belief for many years ...

That aging is the effect of our genes, which regenerate our tissues throughout our lives, being chipped away, small chunk by small chunk, leading to ever degrading body tissues as the genetic information is altered over long periods of time.

Just my own ignorant belief ... but I think it is quite reasonable ...

Gamma Rays anyone ?

[TZ]

3. No its the other way around...

Aging makes our genes work less efficiently. Genes, like anything else biological wear out..Evolutionary biologists for years have known that gene is driven to replicate itself so evolutionary pressures have evolved to make genes work harder and faster during the reproductive age..once one gets past that, you start to see the wear and tear of the genes--they don't process effectively, stop replacing themselves quickly, and are much more likely to mutate..thats why older women who have babies have a higher risk of having a baby with genetic defects.
Aging is being shown to be linked to having genes that wear out at different rates, although obviously physical/environmental stressors have some effect.

[Trajan]

5. What do you mean by 'wear out' ?

They are abraded ? .... tired ? .... they lose layers of molecules ?

Do the genes get wrinkled ?

I do not understand how a gene 'wears out', except by physical damage, which is what I referred to ....

[tinrobot]

6. The telomeres get shorter

From Wikipedia:

A telomere is a region of repetitive DNA at the end of chromosomes, which protects the end of the chromosome from destruction. Derived from the Greek telos (end) and meres (part).

During cell division, the enzymes that duplicate the chromosome and its DNA can't continue their duplication all the way to the end of the chromosome. If cells divided without telomeres, they would lose the end of their chromosomes, and the necessary information it contains. (In 1972, James Watson named this phenomenon the "end replication problem.") The telomere is a disposable buffer, which is consumed during cell division and is replenished by an enzyme, the telomerase reverse transcriptase.

This mechanism usually limits cells to a fixed number of divisions, and animal studies suggest that this is responsible for aging on the cellular level and affects lifespan. Telomeres protect a cell's chromosomes from fusing with each other or rearranging. These chromosome abnormalities can lead to cancer, so cells are normally destroyed when telomeres are consumed. Most cancer is the result of cells bypassing this destruction. Biologists speculate that this mechanism is a tradeoff between aging and cancer.

http://en.wikipedia.org/wiki/Telomere

[Trajan]

7. So this is essentially the same as ...

"That aging is the effect of our genes, which regenerate our tissues throughout our lives, being chipped away, small chunk by small chunk, leading to ever degrading body tissues as the genetic information is altered over long periods of time."

Right ?

[TZ]

9. wear out as in

more and more replication errors occur. You know DNA has a feature where it self repairs right? For instance everytime you go out in sunlight the UV damages your DNA..however it goes over itself and repairs the mistakes. As you age your DNA has a harder and harder time fixing that type of damage, which leads to things like too much or not enough of a certain enzyme being made which can lead to all sorts of problems including diseases. Thats what I mean about DNA "wearing out". And of course you have classic replication errors like trisomy 21 where 3 chromosomes are made during meiosis leading to Down's syndrome in children..a problem that becomes more frequent in women over the childbearing age of 35.
A classic example of how DNA can wear down after ageing and cause chronic disease is something I deal with a disease called essential thrombocythemia..where a defective enzyme pathway (JAK2) causes a "switch" in the bone marrow to stay on allowing far too many platelets to be made.

[undergroundpanther]

2. Don't forget

Stress ,abuse,sunlight exposure,also alter the DNA too.
Stress
http://www.theaustralian.news.com.au/story/0,25197,22402331-27699,00.html
Abuse
http://www.sciencedaily.com/releases/2008/05/080507084001.htm
Sunlight
http://www.fasebj.org/cgi/content/full/16/1/45

Seems just existing in this hostile world tears us apart even down to the biochemical level as life hurts us.

[Phoonzang]

4. So um...if our genes change on their own

during our lifetime, how about changing the genes ourselves to have favorable effects?

[Loisenman]

8. folk wisdom wins

When I was a child, my mother would talk about different genes "coming out" as one got older. Then I learned some biology and became certain this could not be true. But of course now it seems as if her folk wisdom was right.