"I keep saying that chemotherapy is barbaric and in most cases more destructive than the cancer it proposes to cure. Now there's evidence

 thatthe total body assault that chemotherapy provides may have lingering efefcts in woman that will derail a normal life after breast cancer. - Carl"

Chemotherapy-related weight gain may be factor in prolonged fatigue

TAMPA, Fla. – In a follow-up study, researchers at Moffitt Cancer Center and colleagues have found that patients who receive chemotherapy for breast cancer might experience prolonged fatigue years after their therapy. The new study, published in the American Cancer Society's current issue of CANCER, is a follow-up to a study on fatigue and chemotherapy and radiotherapy for breast cancer Moffitt researchers published in CANCER in 2007.

"Fatigue is among the most common symptoms reported by women who are treated for breast cancer," said study corresponding author Paul B. Jacobsen, Ph.D., program leader for Health Outcomes and Behavior at Moffitt.

The 2007 study found that immediately following treatment fatigue was greater in women who had received chemotherapy than in patient groups comprised of women who had received both chemotherapy and radiotherapy, radiotherapy alone, or in groups with no cancer history. Six months after treatment, women in the chemotherapy alone group reported more fatigue than the combination therapy group, the radiotherapy group, or the non-cancer group.

"On the basis of our 2007 study and the results of other studies, we hypothesized that fatigue in the group receiving chemotherapy would diminish over a three-year follow-up period, yet possibly remain higher than fatigue levels for women who had received radiation, combination therapy, or those with no history of cancer," explained Jacobsen.

The recently published follow-up study was comprised of 205 patients who had received chemotherapy compared with 193 women in a control group with no history of cancer. The controls were within five years of age of the cancer patients and lived in the same zip codes as their partner cancer patients. The average age for both groups was 55. Fatigue levels were measured at six months and 42 months.

Their new findings, however, contradicted the expectation that patients receiving chemotherapy would, overtime, experience less fatigue and eventually see their fatigue levels diminish to equal the levels of women in the other two groups.

"Contrary to our expectations, fatigue did not diminish over time for patients in the chemotherapy group," said Jacobsen, who studies the behavioral and psychosocial aspects of cancer, cancer treatment, outcomes, and cancer survivorship. "In some cases, fatigue worsened, and that finding is not consistent with prior research."

Among the possible factors influencing the long-term or worsening fatigue included the potential for weight gain, common among patients who receive chemotherapy and who, according to the researchers, rarely return to their pre-treatment weight.

One variable affecting prolonged or worsening fatigue might involve supportive care, suggested the researchers.

"This finding has important implications for patient education and for fatigue monitoring during follow-up," concluded Jacobsen. "Our results should inform patient education efforts when patients receiving chemotherapy are often told that their fatigue will gradually diminish following treatment. Health care providers may want to communicate to their patients who have received chemotherapy that their fatigue may not improve over time and may worsen."

The researchers concluded that patients should be informed about interventions known to be effective against fatigue post-treatment, such as exercise and cognitive behavior therapy.

The extent to which we are able to activate our muscles voluntarily depends on motivation and will power or the physical condition and level of fatigue of the muscles, for instance. The latter particularly leads to noticeable and measurable performance impairments. For a long time, the research on muscle fatigue was largely confined to changes in the muscle itself. Now, a joint research project between the University of Zurich and ETH Zurich has shifted the focus to brain research. Headed by neuro-psychologist Kai Lutz from the University of Zurich in collaboration with Urs Boutellier from the Institute of Human Movement Sciences and Sport at ETH Zurich, the researchers discovered neuronal processes for the first time that are responsible for reducing muscle activity during muscle-fatiguing exercise. The third and final part of this series of experiments, which was conducted by Lea Hilty as part of her doctoral thesis, has now been published in the European Journal of Neuroscience.

Muscle's nerve impulses inhibit motoric area in the brain

In the initial study, the researchers showed that nerve impulses from the muscle – much like pain information – inhibit the primary motoric area during a tiring, energy-demanding exercise. They were able to prove this using measurements in which study participants repeated thigh contractions until they could no longer attain the force required. If the same exercise was conducted under narcotization of the spinal chord (spinal anesthesia), thus interrupting the response from the muscle to the primary motoric area, the corresponding fatigue-related inhibition processes became significantly weaker than when the muscle information was intact.

In a second step, using functional magnetic resonance imaging, the researchers were able to localize the brain regions that exhibit an increase in activity shortly before the interruption of a tiring, energy-demanding activity and are thus involved in signalizing the interruption: the thalamus and the insular cortex – both areas which analyze information that indicates a threat to the organism, such as pain or hunger.

The third study has now shown that the inhibitory influences on motoric activity are actually mediated via the insular cortex: In tests using a bicycle ergometer, the researchers determined that the communication between the insular cortex and the primary motoric area became more intensive as the fatigue progressed. "This can be regarded as evidence that the neuronal system found not only informs the brain, but also actually has a regulating effect on motoric activity," says Lea Hilty, summing up the current result. And Kai Lutz points to the new research field that now opens up with these results: "The findings are an important step in discovering the role the brain plays in muscle fatigue. Based on these studies, it won't just be possible to develop strategies to optimize muscular performance, but also specifically investigate reasons for reduced muscular performance in various diseases." Prolonged reduced physical performance is a symptom that is frequently observed in daily clinical practice. It can also appear as a side effect of certain medication. However, so-called chronic fatigue syndrome is often diagnosed without any apparent cause.

Alisa and I were doing our standard early morning cardio yesterday. Flipping through the channels of the flat-screen on the wall of our home-gym looking for something to pull our attention for thirty to forty minutes.. and nothing but children's shows that early on a Saturday is what usually challenges us. Then we stumbled upon Public TV artist-turned-art-teacher Bob Ross. Next thing I noticed was instead of waiting for the time to pass, I was stalling to stay on the machine just a little while longer so I could see his next strokes reveal the images that were developing in his mind. All of a sudden the time was effortless and the targeted thirty minutes past and  forty-five minutes seemed to short. It was time to stop yet we both were still clinging to our machines waiting for the mountain-scape to unfold and the snow to be powdered onto the trees in the foreground.

You may want to try this for yourself... find your local PBS channel guide and see when  Bob Ross's show, The Joy of Painting is on. If it airs at a time when you're not doing cardio.. TiVo it. Try watching this during your next cardio session and let me know if it has the same effect of making the time go almost too fast as it did for Alisa and I.

The timing of the release of this research on the heels of my interview with Aubrey de Grey is very promising. Perhaps a day will come when the cash cow of medicine is reversing aging - and thus staving off disease - as opposed to "treating" T2 Diabetes. - Carl

Researchers have shown they can reverse the aging process for human adult stem cells, which are responsible for helping old or damaged tissues regenerate. The findings could lead to medical treatments that may repair a host of ailments that occur because of tissue damage as people age. A research group led by the Buck Institute for Research on Aging and the Georgia Institute of Technology conducted the study in cell culture, which appears in the September 1, 2011 edition of the journal Cell Cycle

The regenerative power of tissues and organs declines as we age. The modern day stem cell hypothesis of aging suggests that living organisms are as old as are its tissue specific or adult stem cells. Therefore, an understanding of the molecules and processes that enable human adult stem cells to initiate self-renewal and to divide, proliferate and then differentiate in order to rejuvenate damaged tissue might be the key to regenerative medicine and an eventual cure for many age-related diseases. A research group led by the Buck Institute for Research on Aging in collaboration with the Georgia Institute of Technology, conducted the study that pinpoints what is going wrong with the biological clock underlying the limited division of human adult stem cells as they age.

"We demonstrated that we were able to reverse the process of aging for human adult stem cells by intervening with the activity of non-protein coding RNAs originated from genomic regions once dismissed as non-functional 'genomic junk'," said Victoria Lunyak, associate professor at the Buck Institute for Research on Aging.

Adult stem cells are important because they help keep human tissues healthy by replacing cells that have gotten old or damaged. They're also multipotent, which means that an adult stem cell can grow and replace any number of body cells in the tissue or organ they belong to. However, just as the cells in the liver, or any other organ, can get damaged over time, adult stem cells undergo age-related damage. And when this happens, the body can't replace damaged tissue as well as it once could, leading to a host of diseases and conditions. But if scientists can find a way to keep these adult stem cells young, they could possibly use these cells to repair damaged heart tissue after a heart attack; heal wounds; correct metabolic syndromes; produce insulin for patients with type 1 diabetes; cure arthritis and osteoporosis and regenerate bone.

The team began by hypothesizing that DNA damage in the genome of adult stem cells would look very different from age-related damage occurring in regular body cells. They thought so because body cells are known to experience a shortening of the caps found at the ends of chromosomes, known as telomeres. But adult stem cells are known to maintain their telomeres. Much of the damage in aging is widely thought to be a result of losing telomeres. So there must be different mechanisms at play that are key to explaining how aging occurs in these adult stem cells, they thought.

Researchers used adult stem cells from humans and combined experimental techniques with computational approaches to study the changes in the genome associated with aging. They compared freshly isolated human adult stem cells from young individuals, which can self-renew, to cells from the same individuals that were subjected to prolonged passaging in culture. This accelerated model of adult stem cell aging exhausts the regenerative capacity of the adult stem cells. Researchers looked at the changes in genomic sites that accumulate DNA damage in both groups.

"We found the majority of DNA damage and associated chromatin changes that occurred with adult stem cell aging were due to parts of the genome known as retrotransposons," said King Jordan, associate professor in the School of Biology at Georgia Tech.

"Retroransposons were previously thought to be non-functional and were even labeled as 'junk DNA', but accumulating evidence indicates these elements play an important role in genome regulation," he added.

While the young adult stem cells were able to suppress transcriptional activity of these genomic elements and deal with the damage to the DNA, older adult stem cells were not able to scavenge this transcription. New discovery suggests that this event is deleterious for the regenerative ability of stem cells and triggers a process known as cellular senescence.

"By suppressing the accumulation of toxic transcripts from retrotransposons, we were able to reverse the process of human adult stem cell aging in culture," said Lunyak.

"Furthermore, by rewinding the cellular clock in this way, we were not only able to rejuvenate 'aged' human stem cells, but to our surprise we were able to reset them to an earlier developmental stage, by up-regulating the "pluripotency factors" – the proteins that are critically involved in the self-renewal of undifferentiated embryonic stem cells." she said.

Next the team plans to use further analysis to validate the extent to which the rejuvenated stem cells may be suitable for clinical tissue regenerative applications.

The study was conducted by a team with members from the Buck Institute for Research on Aging, the Georgia Institute of Technology, the University of California, San Diego, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, International Computer Science Institute, Applied Biosystems and Tel-Aviv University.

Citation:

Inhibition of activated pericentromeric SINE/Alu repeat transcription in senescent human adult stem cells reinstates self-renewal. Cell Cycle, Volume 10, Issue 17, September 1, 2011