Aging

[Gyrase]

Hello, What do we know about aging? What are latest findings? I start but my knowledge on this issue may be a few years old ...

1- One of theories is telomere shortening that as far as I know has been shown is related to some forms of pathologic aging. But not all cells divide at the same rate, what about neurons what cause them to be lost in process of aging

 

2- It has been suggested that some proteins known as Heat shock proteins that help to preserve conformation of cellular proteins may be associated with aging. Their expression decrease with aging. Dose it mean if we could lower temperature of body and prevent local hyperthermia we would much longer. If I recall correctly it has been shown that in some worms lowering body temperature + very low calorie regime can multiply their life period, can this be true also for complex primates ?

 

3- Free radical especially oxygen, ROS(Reactive Oxygen Species) is another prime suspect. Some damages to DNA may be unrepairable and accumulate overtime, also damages to cell membrane can be important. But Cells have very sophisticated defense mechanisms against ROS. If we would supply huge amount of none toxic anti oxidants could it multiply our life period? It has been recommended to use extra amount of anti oxidants like vitamin E as supplements but it had not huge effect on humans' life period.

 

regards,

[Hobbz]

I'm a little familiar with the Free Radical Theory of aging. It's not so much that the ROS molecules are damaging proteins and membranes because those are turned over thousands of times in a life span of many organisms. It's more about the accumulation of mutations that occur in DNA due to ROS. Over time the mutations build up and can cause apoptosis, necrosis, senescence or carcinogenesis. One interesting observation in biology is the average lifespan of animals plotted against the resting heart. The slower the heart rate the longer the animal lives.

[Gyrase]

ROS can cause cancer but not all old people die from cancer and many of cancers are known to be genetically inherited. ROS is definitely a prime suspect. maybe the price that an animal pays for, to be faster and more agile(more oxygen) is reducing life Span.

All aerobic organisms had to fight the damages that they cause from the start of aerobic life but also defense mechanisms against ROS are very sophisticated and why anti oxidation chemicals like vitamin E do not have a sensible effect increasing our life span. can you think about an experiment that can shed light exactly to what extent ROS can cause aging?

 

cheers,

DG

[Hobbz]

A couple things about oxygen and ROS.

 

The more oxygen living cells are exposed to the more damaging ROS molecules are, which has been shown irradiating cells exposed to varying amounts of oxygen. So perhaps the more oxygen an organism is exposed (faster heartbeat) the faster ROS can hurt the organism.

 

Cancer is one pathway to death and exposure to ROS certainly increases its likelihood. ROS has also been suggested to play a role in artherosclorosis as well.

 

Funny you mentioned vitamin E, because that is the one supplement that has been shown to decrease the likelihood of cancer and I think artherosclorosis as well in epidemiology studies. Other vitamins and supplements don't have near as strong of evidence as vitamin E.

 

Several experiments have been done in cell cultures with non-immortalized cell lines, cells that have a finite number of divisions. Cells that have upregulated antixodant enzymes will divide longer than normal cells before they go into senescence.

 

And that reminds of another point, are we talking about longevity (lifespan) or aging (losing the capacity to function properly). I'm assuming aging since of course since that's what this thread is titled. Anyway, the role ROS may play role in senescence which some people argue is the cause of aging. And ROS may bring about senescence by pushing the genome to accumulate more mutations which could upregulate genes that prevent cell division.

 

So one experiment could be to look at several cell lines and determine if there is a common amount of mutations in the genome they acquire in order for them to senesce. Then upregulate antioxidant enzymes which will allow them to divide longer and see if they acquire more, less or the same number of mutations before they senesce. I would hypothesize that they(upregulated antioxidant enzyme cells) would acquire the same number of mutations at senescence and have a greater dividing potential.

[Gyrase]

Hobbz, we are not talking about reducing likelihood of some illnesses by some percents and increasing life-span for some years. we are talking about process of aging that if it is understood it can increase life span of an organism dramatically for ours I don't mean 10,20,50 years but maybe 400,800,... as I said in some worms with usually short lifespan, lowering body temp+ low calorie diet could multiply their life span if I remember correctly more than x4. As I said my knowledge is a few years old but as far as I remember first there were much enthusiasms about vitamin E but there were also some researches that questioned previous findings that vitamin E can lower risk of cancer and heart disease.

we are not talking about cancer that usually appears at last stages of organism life we are talking about process of aging that if slows can multiply our life span at very least.

you talked about effect of upregulated antioxidant enzymes on number of cell division in vitro. can you be more specific which enzyme, which cell, possibly refer me to abstract of the article? I especially interested about new researches.

 

cheers,

DG,

[Hobbz]

Here are some interesting papers I found and the one I was referring to earlier was the first paper noted below. They used superoxide dismutase and found that it increased the doubling capacity of the cells. I think the other papers offer some possible explanations for the first however I haven't had much time to look over them.

 

"Manganese superoxide dismutase protects the proliferative capacity of confluent normal human fibroblasts" Antioxid Redox Signal.

 

"H2O2 accelerates cellular senescence by accumulation of acetylated p53 via decrease in the function of SIRT1 by NAD+ depletion." Cell Physiol Biochem.

 

"Cytoplasmic localization and ubiquitination of p21Cip1 by reactive oxygen species" Biochemical and Biophysical Research Communications

 

Enjoy.

 

Sorry I made a mistake the first paper can be found in the Journal of Biological Chemistry and not Antioxidants and Redox Signaling.