News flashes are posted here frequently to keep you up-to-date with the latest advances in health and longevity. We have an unparalleled track record of breaking stories about life extension advances.
Androgen insufficiency may underlie a number of conditions
The September/October 2009 issue of the Journal of Andrology published a review by researchers from Boston University School of Medicine in collaboration with researchers from Lahey Clinic Northshore in Peabody, Massachusetts which concludes that a decline in androgens could be the cause of a number of age-related diseases and conditions, such as metabolic syndrome, diabetes, cardiovascular disease and erectile dysfunction. Androgens are steroid hormones which include testosterone that control the development and maintenance of male characteristics. Reduced testosterone levels have in men been associated with a greater risk of mortality over a given time period.
In their article, entitled, "The Dark Side of Testosterone Deficiency," Boston University School of Medicine professor of biochemistry and urology Abdulmaged M. Traish, MBA, PhD, and his colleagues discuss the relationships between low testosterone levels and cardiovascular risk factors, citing numerous reports published between 1980 and 2008 to support their hypothesis. The authors trace androgen deficiency’s associations with the metabolic syndrome components of glucotoxicity and insulin resistance, lipotoxicity, and inflammatory factors, all which contribute to endothelial dysfunction.
"In view of the emerging evidence suggesting that androgen deficiency is a risk factor for cardiovascular disease, androgen replacement therapy could potentially reduce cardiovascular disease risk in hypogonadal men," stated Dr Traish. "It should be emphasized, however, that androgen replacement therapy should be done with very thorough and careful monitoring for prostate diseases.”
The authors recommend long-term, placebo-controlled clinical trials of testosterone in men who are deficient in the hormone. "Although challenges might lie ahead regarding how data from such clinical trials are to be properly interpreted and whether long-term safety can be established with testosterone supplementation, these findings warrant definite investigation into the beneficial role that androgens might have in preventing cardiovascular risk in androgen-deficient men," Dr Traish added.
Resveratrol suppresses ovarian cancer growth in laboratory studies
In the September 15, 2009 issue of the journal Cancer Research, a team from Korea reports that resveratrol, a compound found in grapes and red wine, reduces the proliferation of cultured human ovarian cancer cells as well as the growth of ovarian cancer tumors grafted into mice.
Young-Joon Surh of Seoul National University in South Korea and colleagues treated three human ovarian cancer cell lines (PA-1, TOV-112D and SK-OV-3) with five concentrations of resveratrol for 12, 24 and 48 hours, and observed that resveratrol dose and time-dependently decreased cell viability. The PA-1 cancer cell line was the most susceptible to resveratrol’s effects. Further testing of cells from the PA-1 line that were stimulated with insulin or serum determined that resveratrol induced apoptosis (programmed cell death) and decreased the expression of the oncogene eEF1A2, which protects against apoptosis.
When the researchers implanted ovarian cancer cells into mice, intraperitoneal administration of resveratrol decreased average tumor volume and mass compared to animals treated with a control substance. Tumor growth was associated with an increase in eEF1A2 expression that was reduced in animals that received resveratrol.
In their introduction to the article, the authors remark that resveratrol has been found to prevent angiogenesis (new blood vessel formation), induce autophagocytosis and lower chemotherapy resistance in ovarian cancer cells.
“The present study reveals that resveratrol significantly inhibits the growth of PA-1 human ovarian cancer cells in association with reduced eEF1A2 expression, suggesting this peptide elongation factor as a novel molecular target of resveratrol,” the authors conclude.
Coenzyme Q10 trial planned
A Phase III clinical trial of coenzyme Q10 (coQ10) in Parkinson’s disease patients is being planned by Rush University Medical Center to help confirm the ability of the compound to slow the disease’s progression. The trial, funded by the National Institutes of Health and the National Institute of Neurological and Disorders and Stroke, will add to the findings of an earlier study that revealed a reduction in the decline of motor function and the ability to carry out activities of daily living in early stage Parkinson’s disease patients who received 1,200 milligrams coenzyme Q10 for 16 months. The researchers intend to test 1,200 and 2,400 milligrams coQ10 in the form of a chewable wafer containing vitamin E, to be administered for 16 months to Parkinson’s disease patients at 60 centers in the United States and Canada. Participants will be evaluated for tremor, stiffness of the limbs and trunk, balance and coordination, speed of movements, ability to perform daily activities, quality of life, and the need to take medication.
Parkinson’s disease patients have impaired mitochondria, which are the energy-producing organelles of the cells. In addition to its role as an antioxidant, coenzyme Q10 is involved in mitochondrial energy production, therefore, boosting coQ10 levels may help improve mitochondrial function. Studies of Parkinson’s disease patients have found reduced levels of coQ10, and laboratory research has shown a protective effect for coQ10 in the area of the brain that is damaged by the disease.
"At present, the very best therapies we have for Parkinson's can only mask the symptoms – they do not alter the underlying disease," commented neurologist and movement disorder specialist Dr Katie Kompolitis, who was involved in the earlier study of coQ10 in Parkinson’s disease. "Finding a treatment that can slow the degenerative course of Parkinson’s is the holy grail of Parkinson's research."
Diabetes drug works with chemotherapy to destroy cancer stem cells
In an article published online on September 14, 2009 in the journal Cancer Research, Harvard researchers report that a combination of the antidiabetic medication metformin and the chemotherapy drug doxorubicin shrinks cancer stem cells in vitro, and reduced tumor mass in a mouse model of breast cancer.
“The cancer stem cell hypothesis suggests that tumors contain a small number of tumor-forming, self-renewing, cancer stem cells within a population of nontumor-forming cancer cells,” write Kevin Struhl, PhD and his colleagues in their introduction to the article. “Unlike most cells within the tumor, cancer stem cells are resistant to well-defined chemotherapy, and after treatment, they can regenerate all the cell types in the tumor through their stem cell–like behavior. For this reason, drugs that selectively target cancer stem cells offer great promise for cancer treatment, although none are known at present.”
The research team, led by Harvard postdoctoral fellows Heather Hirsch and Dimitrios Iliopoulos, observed that the metformin-doxorubicin combo killed both cancer stem cells and non-stem cancer cells in four cultured breast cancer lines. In tests with mice into which breast cancer cells were grafted, pretreatment with metformin prevented the cells from forming tumors. And in an experiment in which breast tumors were allowed to grow for ten days, metformin and doxorubicin combined decreased tumor mass more rapidly and delayed relapse longer than doxorubicin alone.
"There is a big desire to find drugs specific to cancer stem cells," stated Dr Struhl, who is the David Wesley Gaiser professor of biological chemistry and molecular pharmacology at Harvard Medical School. "The cancer stem cell hypothesis says you cannot cure cancer unless you also get rid of the cancer stem cells. From a purely practical point of view, this could be tested in humans. It's already used as a first-line diabetes drug."
Green tea catechins strengthen bone
In the August 26, 2009 issue of the Journal of Agricultural and Food Chemistry, Ping Chung Leung and associates at the Chinese University of Hong Kong report that green tea catechins stimulate bone growth and increase mineralization in cell cultures.
Dr Leung's team administered varying concentrations of the tea catechins epigallocatechin (EGC), gallocatechin (GC), and gallocatechin gallate (GCG) to cultured rat osteoblast-like cells. After four days they discovered that EGC dose-dependently increased the activity of alkaline phosphatase, an enzyme that increases bone growth, by 79 percent. Bone matrix mineralization was found to be increased upon evaluation after six days.
In an experiment with mouse cells, 10 micrograms per mole EGC significantly inhibited the formation of osteoclasts, which are the cells responsible for breaking down bone. Gallocatechin and gallocatechin gallate also inhibited osteoclasts, but at a higher concentration.
The researchers remarked that an abnormal increase in osteoclast differentiation is one of the causes of bone erosion and osteoporosis, and that reactive oxidative species could play an important signaling role in this process. Antioxidants such as those occurring in green tea which protect against reactive oxygen species may thus help prevent bone break down.
"In summary, our study has provided the first laboratory evidence on the bone promotion effects of the green tea catechin EGC as was demonstrated by the promotion of osteoblastic differentiation and inhibition of osteoclast formation," the authors announce. "Moreover, GC and GCG can effectively inhibit osteoclastogenesis."
"Our observations would serve as groundwork for further studies," they write. "Studies could explore the signaling pathways and gene expressions upon administration of these catechins on in vitro systems."
Green tea compound helps preserve platelets, skin, cartilage
The latest issue of the journal Cell Transplantation contains three articles describing the ability of the green tea polyphenol epigallocatechin-3-O-gallate (EGCG) to help extend the shelf-life of stored human and animal tissue.
The research was led by Dr Suong-Hyn Hyon, who is an associate professor at Kyoto University's Institute for Frontier Medical Sciences. In one article, Dr Hyon and associates described the ability of EGCG to help preserve blood platelets, which are only stored for 3 days in Japan. The addition of EGCG prolonged the platelets' ability to aggregate and helped maintain their affinity for surface receptors, which improved their viability after 6 days compared to untreated platelets. "EGCG may lead to an inhibition of platelet apoptosis and lower rates of cell death, offering a potentially novel and useful method to prolong platelet storage period," Dr Hyon observed.
In another study, EGCG improved the storage of frozen rat skin, a finding that could positively impact the preservation of human skin used for grafting. "To provide best outcomes, skin grafts must be processed and stored in a manner that maintains their viability and structural integrity until they are needed for transplantation," Dr Hyon explained. "Transplant dysfunction often occurs as the result of oxidation. A better storage solution could prevent this."
For the study, rat skin treated with EGCG was preserved at 4 degrees Celsius for 2, 8 or 24 weeks and transplanted to nude mice. "The storage time of skin grafts was extended to 24 weeks by cryopreservation using EGCG and the survival rate was almost 100 percent," Dr. Hyon remarked.
A third article describes how rabbit cartilage stored for 2 weeks in a medium containing EGCG was associated with high cell viability and improved retention subsequent to grafting.
"These studies highlight the benefits of using natural compounds such as ECGC to enhance the preservation of stored tissues, possibly due to their antioxidative properties," Cell Transplantation guest editor Dr Naoya Kobayashi concluded.
New method monitors tumor oxidative stress
A report published online on September 10, 2009 in the Proceedings of the National Academy of Sciences describes the development of a new technique to evaluate oxidative stress levels in cancer cells. Oxidative stress is a condition that results from an abundance of highly reactive oxygen-containing molecules known as free radicals, which can fuel tumor growth. Treatment with antioxidants, which inhibit free radicals, has shown mixed results in cancer research, possibly due to differing oxidative stress levels among patients. A technique that enables the monitoring of tumor cell growth pathway-associated oxidative stress could improve the success of antioxidant therapy against cancer.
Young Ho Seo, PhD and Kate Carroll, PhD of the University of Michigan’s Life Sciences Institute in Ann Arbor report their development of a method of detecting sulfenic acid in proteins, which is the initial oxidation product of the amino acid cysteine’s reaction with hydrogen peroxide, a well known pro-oxidant. The researchers used a chemical probe to tag sulfenic acid for recognition by a labeled antibody, enabling sulfenic acid levels to be measured in cultured breast cancer cells. They discovered a different pattern of sulfenic acid modifications in each breast tumor type investigated.
"For each line, we saw a very distinct pattern of sulfenic acid modifications, indicating different oxidative stress levels and hinting at differences in the underlying molecular events associated with tumor growth," stated Dr Carroll, who is assistant professor of chemistry at UM. "Whether the patterns we see will correlate with response to antioxidant treatment or other therapies that modulate oxidative stress level remains to be seen, but now we at least have a way to investigate that question."
Future research planned by Drs Carroll and Seo will identify specific cell proteins modified during oxidative stress and determine whether they are involved in cancer.
Longer telomeres found in tea drinkers
A report published online on August 12, 2009 in the British Journal of Nutrition revealed that men who regularly drink tea have telomeres that are longer than those who don’t.
Telomeres are DNA sequences that cap the ends of chromosomes, which shorten with the aging of the cell. Telomere length has been proposed as a biomarker of aging. Environmental and lifestyle factors that affect oxidative stress levels and inflammation influence the rate of cell turnover and, consequently, telomere length.
The current study included 976 men and 1,030 women who participated in a health survey from 2001 to 2003. White blood cell telomere length was measured in DNA extracted from blood samples. Food frequency questionnaires were used to evaluate the intake of food from 13 groups and Chinese tea.
A significant difference in telomere length was observed upon comparison of men who consumed more than three cups of tea per day with those whose tea intake was lowest at an average of a quarter cup or less. The difference corresponded to approximately 5 years of life. Among women, no association between tea drinking and telomere length was observed, however, a greater intake of oils and fats had a borderline association with shorter telomeres.
The authors, from the Chinese University of Hong Kong, write that the antioxidative properties of tea may protect telomeres from the oxidative damage that occurs with aging. The survival advantage experienced by women due to hormones and other factors that may provide greater resistance to oxidative stress could explain the reduced impact of diet on telomere length suggested by the current study. The researchers recommend further research to elucidate the mechanisms by which tea and other dietary components influence telomere length.
Genetic mutation finding supports oxidative stress' role in aging
A report published online during the week of September 6-12, 2009 in the Proceedings of the National Academy of Sciences confirmed the impact of oxidative damage on the body's genetic material, which causes mutations that lead to aging, cancer and other disordered states.
Researchers at Oregon State University, Indiana University, the University of Florida and the University of New Hampshire tracked genetic mutations in the roundworm C. elegans for 250 generations: the equivalent of 5,000 human years. The worms accumulated 391 genetic mutations, which is over 10 times as many as have been discovered in similar studies. The majority of mutations were linked to guanine, a DNA nucleotide that is especially sensitive to oxidative damage.
"Most life on Earth depends in some form on oxygen, which is great at the production of energy," explained lead researcher and Oregon State University assistant professor of zoology Dee Denver. "But we pay a high price for our dependence on oxygen, because the process of using it is not 100 percent efficient, and it can result in free oxygen radicals that can damage proteins, fats and DNA. And this process gets worse with age, as free radicals accumulate and begin to cause disease."
"Genetic mutations in animals are actually pretty rare, they don't happen very often unless they are induced by something," she noted. "The value of using this roundworm is that it reaches reproductive age in about four days, so we can study changes that happen through hundreds of generations, using advanced genome sequencing technology."
"The research showed that the majority of all DNA mutations bear the signature of oxidative stress," Dr Denver concluded. "That's exactly what you would expect if you believe that oxidative stress is an underlying cause of aging and disease."
Virus identified in prostate cancer cells
In an article published online on September 7, 2009, in the Proceedings of the National Academy of Sciences, researchers at the University of Utah and Columbia University report the discovery in prostate cancer cells of a virus known to cause cancer in animals.
Acting on previous findings from the University of California, San Francisco, and the Cleveland Clinic, University of Utah associate professor of epidemiology Ila R. Singh, MD, PhD and her colleagues compared tissue samples from 233 prostate cancer patients and 101 men with benign prostate hypertrophy. They found the gammaretrovirus known as xenotropic murine leukemia virus-related virus (XMRV) in 27 percent of the prostate cancer specimens compared with 6 percent of the benign samples. The viral proteins were nearly all located in malignant cells, indicating that infection could be involved in tumor formation.
“Gammaretroviruses (of which XMRV is the newest member) cause cancer in animals by transforming the cells they infect,” Dr Singh told Life Extension. “Thus finding the virus in malignant cells is compatible with classical mechanisms of tumor formation followed by retroviruses.”
The discovery could add prostate cancer to a number of malignancies caused in many cases by infectious agents, including cervical cancer, stomach cancer, and lymphoma. If XMRV is shown to cause prostate cancer, it could enable researchers to develop diagnostic tests and antiviral treatments. Another promising area of research concerns the prevention of viral transmission.
"We found that XMRV was present in 27 percent of prostate cancers we examined and that it was associated with more aggressive tumors," stated Dr Singh. "We still don't know that this virus causes cancer in people, but that is an important question we're going to investigate."
"We have many questions right now," Dr Singh added, "and we believe this merits further investigation."
Vitamin C needed for brain development
In the September, 2009 issue of The American Journal of Clinical Nutrition, a team from the University of Copenhagen suggests that pregnant women with inadequate vitamin C intake risk giving birth to infants with impaired mental development.
Professor Jens Lykkesfeldt and colleagues fed 6 to 7 day old guinea pigs diets containing sufficient or insufficient amounts of vitamin C for two months. Guinea pigs are one of the few animals, similar to humans, that do not make their own vitamin C. At the end of the treatment period, the brains of the animals that received vitamin C insufficient diets were found to have 30 percent fewer hippocampal neurons and significantly worse spatial memory compared with those that received a normal diet.
“Our data show that vitamin C deficiency in early postnatal life results in impaired neuronal development and a functional decrease in spatial memory in guinea pigs,” the authors conclude. “We speculate that this unrecognized effect of vitamin C deficiency may have clinical implications for high-risk individuals, such as in children born from vitamin C-deficient mothers.”
Newborns’ brains may be especially vulnerable to even small reductions in vitamin C. In studies utilizing mouse fetuses, those that were unable to transport vitamin C developed brain damage resembling that of premature infants.
“We may thus be witnessing that children get learning disabilities because they have not gotten enough vitamin C in their early life,” Dr Lykkesfeldt commented. “This is unbearable when it would be so easy to prevent this deficiency by giving a vitamin supplement to high-risk pregnant women and new mothers."
Dr Lykkesfeldt’s team is currently evaluating the effect of vitamin C deficiency in early pregnancy, and whether the damage can be reversed after birth.
Know your risks
A new tool developed by Carnegie Mellon University enables anyone with internet access to determine their average risk of dying from major causes and compare those risks with other age groups, races and geographic areas.
Former Carnegie Mellon professor David Gerard along with site developer Paul Fischbeck, who is a professor of social and decision sciences and engineering and public policy, incorporated public statistics from the United States and Europe into a web-based tool in which a “MicroMort” is used as a unit of a one-in-a-million chance of dying within the next year. A cause of death with a lower number of MicroMorts for a specified gender, race, age group or geographic area means a lower risk of dying has been calculated for that group.
The data reveal a dramatically higher risk of dying within the next year for men, who have a much higher risk of fatal heart disease, accidents, homicides and suicides than women. When Western Europeans were compared to residents of the U.S., they were shown to have a higher risk of dying from prostate and breast cancer, however Americans have a greater risk of dying from lung cancer death and causes related to obesity. "Most Americans don't have a particularly good understanding of their own mortality risks, let alone ranking of their relevant risks," noted Dr Gerard, who is currently an associate professor of economics at Lawrence University in Appleton, Wisconsin.
Drs Fischbeck and Gerard believe that their tool could be of use to those engaged in the current health care policy discussion taking place in the U.S. "We believe that this tool, which allows anyone to assess their own risk of dying and to compare their risks with counterparts in the United States and Europe, could help inform the public and constructively engage them in the debate," Dr Fischbeck stated.