More Clues to Aging - Our bodies, our cells

[RedOnce]

Aging is characterized by a gradual functional decline of all organ systems.

"Cellular senescence" is the phenomenon where cells lose the ability to divide in response to DNA damage that cannot be repaired. Whether or not cellular senescence contributes to organismal aging has been controversial, but now the science is beginning to come in.

Skeptics say 'Show us the evidence.' "The first solid evidence is in this study. These initial findings won't settle the debate, but they make a strong case." Dr. Sedivy commented.

Our bodies, our cells

February 3, 2006

In the journal Science, biologists from Brown University reported a connection between the age of baboons and the number of aging cells in their skin, boosting the theory that cellular senescence is associated with an aged body. Replicative senescence occurs when cells lose their ability to divide after a number of replications. Senescent cells are associated with skin wrinkles, weakened immune response and other age related conditions and diseases.

Professor of medical science John Sedivy and colleagues examined skin samples from the forearms of 30 baboons aged 5 to 30 for biomarkers of cellular aging. They found an exponential increase in DNA double-strand breakage with the animals' increasing age, reaching 30-35 percent in the oldest animals. The most important biomarker, telomere dysfunction-induced foci (TIF) which show that telomeres have shrunk to the extent that cell division is halted, were found in 4 percent of the tissue cells of 5 year old baboons and in up to 20 percent of the cells of the 30 year olds.

The authors observed that telomeric DNA damage may not be entirely due to replicative exhaustion, and note that oxidative stress increases the rate of telomere shrinkage.

http://www.lef.org/whatshot/index.html#lccr



2006 Feb 2;
Cellular Senescence in Aging Primates.

Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM.

Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02903, USA.

"We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching values of >15% in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated (ATM) kinase and heterochromatinized nuclei, confirming their senescent status."

PMID: 16456035

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16456035&query_hl=2&itool=pubmed_docsum





Related Studies:

2006 Feb 6; Epub 2006 Jan 19.
Downregulation of protein kinase CKII is associated with cellular senescence.

"Taken together, these results suggest that downregulation of CKII activity is tightly associated not only with cellular senescence but also with organism aging."

PMID: 16442104

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16442104&query_hl=2&itool=pubmed_docsum



2006 Feb 1;5(3)
p63: A New Link Between Senescence and Aging.

"The recent discovery that loss of the p53-related protein p63 induces cellular senescence and causes features of accelerated aging provides further evidence that cellular senescence is intimately linked with organismal aging, and identifies p63 as a key regulator of both of these processes."

PMID: 16434880

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16434880&query_hl=2&itool=pubmed_docsum

[Talismom]

1. This is one of the areas I study. Another important finding is that

factors (radiation, toxins, oxygen damage, many oncogenes, to name a few)that cause cellular stress can induce cellular senescence without decreasing telomere length.

These senescent cells switch from a program of cell division to one of massive secretion and some of the products secreted can favor cancer formation in surrounding tissues. This is thought, by many, to be why cancer increases with age. Cell senescence is said to be a double-edged sword. In youth it stops damaged cells from dividing uncontrollably and so prevents cancer, letting one live long enough to reproduce. Later on these long senescent cells become more numerous and this favors cancer development in old age.

Judith Campisi, at Lawrence Berkeley National Laboratory refers to it as antagonistic pleiotropy--a fancy way of saying that we pay a price for holding off cancer long enough to reproduce. Lots of evolution in this subject baby!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T31-4DKJJB7-8&_coverDate=01%2F01%2F2005&_alid=366522936&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4933&_sort=d&view=c&_acct=C000002898&_version=1&_urlVersion=0&_userid=27541&md5=dbef03248add67b7d1108703af23e0c5

[RedOnce]

2. Most interesting finding! Thank you for posting it.

[Talismom]

3. Thank you for the heads-up on the newest studies! n/t

[Wind Dancer]

7. Thanks, Talismom.

Your posts are some of the most informative on DU, I look forward to reading more about these important discoveries.

:hi:

[RedOnce]

10. Thank you for bringing up Judith Campisi. Here is a current article

about her with some interesting comments and quotes.

The Age of Senescence

The Scientist Feb. 2006
Judy Campisi's work on cancer may reveal the secrets of (not) getting older
http://www.the-scientist.com/2006/2/1/60/1/


Perhaps the strongest evidence, published when Campisi moved to the West Coast, was her demonstration that senescent cells not only exist in vivo but also accumulate in aging tissue. What’s more, she and her colleagues have found that in culture, these nonreplicating cells are far from inert. They produce a plethora of unpleasant proteins that can, among other things, destroy the structural integrity of the tissue that surrounds them.

Whether senescent cells contribute to aging, notes Miller, “is the kind of scientific question that most people in the field decided not to pay attention to and hoped others would stop asking.” But Campisi thrives on attacking such puzzles. Take, for example, the observation that mouse cells and human cells behave differently in culture. Normal human fibroblasts divide maybe 50 or 60 times before they senesce; mouse cells, on the other hand, divide 5 or 10 times and then either die or become transformed.


“People had known about that phenomenon for 20 years and sort of ignored it,” says Miller. Campisi investigated and found that mouse cells are more sensitive to oxidative damage than human cells and that the oxygen concentration used in the typical incubator (about 20%) is more than mouse cells can handle. The observation raises a tantalizing possibility, says Campisi: “ One of the reasons why mice live so much shorter and develop cancer much more readily than humans is because they’re much more oxygen sensitive.”

In experiments in tissue culture and in mice, she finds that proteins produced by senescent fibroblasts, including proteases, growth factors, and even molecules that promote angiogenesis can fuel malignancy, encouraging premalignant cells to become fully cancerous and form tumors that can kill an animal. “That was a very important observation,” notes DePinho.

[JohnWxy]

11. Regarding Oxygen sensitivity ..

I wonder if there wouldn't be a benefit to reducing production of excess Oxygen Free Radicals by helping the Krebs energy to produce fewer OFRs, or to help reduce production of OFR in hypoxic conditions in the cells. To that end research on Idebenone seems encouraging.


http://smart-drugs.net/JamesSouth-idebenone.htm


Co Q10’s pro-oxidant action

"When blood flow is seriously reduced to any part of the body, as in a heart attack, stroke, trauma, shock, or chronic poor blood circulation- cellular/ mitochondrial oxygen (O2) levels quickly drop in the affected region. Yet because oxygen is seven to eight times more soluble in the lipid zones of cell membrane, compared to the watery compartments of the cell, there is still sufficient oxygen remaining in the membranes of cells and organelles, as well as in the electron transport chain, to auto-oxidize Co Q10. As the Co Q10 auto-oxidizes, hydrogen peroxide, superoxide and hydroxl free radicals are rapidly formed in massive numbers. These free radicals quickly damage cell/ organelle structure and function, as well as rapidly halt ATP energy generation by the electron transport chain.

Brain and spinal cord cells are especially prone to such damage, and may be irreparably damaged or even destroyed within minutes.

Why Idebenone is superior to Co Q10

Studies have shown that under the same cellular low oxygen conditions that cause Co Q10 to act as a pro-oxidant producer of damaging free radicals, Idebenone prevents the free radical dam-age and maintains relatively normal cell ATP levels. In short, while Idebenone can effectively substitute for Co Q10's positive and life essential functions, it doesn't have Co Q10's free radical producing and energy crashing "dark side" which occurs under hypoxic (low oxygen) conditions."

[Warpy]

4. The good news is that you can lengthen those telomeres

The bad news is that it only benefits succeeding generations, not yourself. They've found that people from families whose history includes delayed marriage and childbearing produced offspring with longer telomeres. It makes sense, the way for a genetic line to preserve itself if the humans carrying it are uncooperative and refuse to marry at 16.

[RedOnce]

5. Cool evolutionary feature!

I wonder if there are ways to slow our rate of telomere shrinkage?

Plus as Talismom points out "Another important finding is that factors (radiation, toxins, oxygen damage, many oncogenes, to name a few)that cause cellular stress can induce cellular senescence without decreasing telomere length." So, there appears to be hope for prevention independent of telomere length.

[Talismom]

8. I'd love to see that original source! n/t

[Warpy]

9. So would I

It was in print in the Lancet about 10 years ago, if my memory is accurate. Since I'm suffering from CRS Syndrome, it may not be.

There may be something of it left online, but probably not.

[Wind Dancer]

6. Thanks for this wealth of information!

I've bookmarked these links for further reading.