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March 2016

By Life Extension

Testosterone Improves Insulin Sensitivity in Diabetic Men

Testosterone Improves Insulin Sensitivity in Diabetic Men

Diabetes Care reported the outcome of a trial that revealed a beneficial role for testosterone treatment in male diabetics.*

The trial included 94 type II diabetic men, 44 of whom had low testosterone levels and reduced insulin signaling genes indicative of decreased insulin sensitivity. Participants with low testosterone received a weekly testosterone injection or a placebo for 24 weeks. Body weight, body fat, markers of inflammation, insulin sensitivity, and other factors were assessed before and after treatment.

At the end of the trial, men who received testosterone experienced an average loss of body fat of over six pounds and an equal increase in muscle mass. They also had lower levels of the inflammatory markers C-reactive protein (CRP), interleukin-1b, and TNF-a. “Most importantly, we saw a dramatic increase in insulin sensitivity, demonstrated by a 32% increase in the uptake of glucose by tissues in response to insulin,” lead researcher Paresh Dandona reported.

Editor’s Note: “Testosterone treatment for men, where indicated, will improve sexual function and increase skeletal muscle strength and bone density,” Dr. Dandona noted.“This is the first definitive evidence that testosterone is an insulin sensitizer and hence a metabolic hormone.” This study corroborates what Life Extension has published for decades about the ability of testosterone replacement in male diabetics to improve insulin sensitivity and reduce inflammatory markers.

Reference

*Diabetes Care. 2015 Nov 30.

Aspirin Anticancer Mechanism Uncovered

Aspirin Anticancer Mechanism Uncovered

Findings obtained from a trial reported in Cancer Epidemiology, Biomarkers, and Prevention reveal a previously unknown mechanism for aspirin in cancer prevention.*

Subjects received 325 mg aspirin or a placebo for 60 days. Using a technique known as metabolic profiling, levels of 363 metabolites involved in most human biochemical pathways were measured in all participants.

Cornelia Ulrich, PhD, and associates found that aspirin decreased levels of both forms of the onco-metabolite 2-hydroxyglutarate by 12% among the trial subjects and by up to 34% in colorectal cancer cell lines. (Increased levels of 2-hydroxyglutarate have been found in blood and brain cancers.) The researchers also determined that salicylate, the primary aspirin metabolite, inhibits an enzyme involved in 2-hydroxyglutarate production.

“It is really exciting that aspirin, which can work in colorectal cancer prevention, is now linked to a new pathway that has shown to be relevant for cancer formation,” commented Dr. Ulrich.

Editor’s Note: It has been hypothesized that aspirin’s anti-inflammatory and antithrombotic effects are behind its apparent ability to protect against some cancers. “This new study suggests that aspirin is playing a key role in interrupting multiple pathways that are linked to cancer development,” Dr. Ulrich stated. “Here we show both in the clinic and laboratory that a reduction in 2-hydroxyglutarate may identify a new mechanism for aspirin in cancer prevention.”

Reference

*Cancer Epidemiol Biomarkers Prev. 2015 Nov 19.

Omega-3 Fatty Acids Decrease Risk of Rheumatoid Arthritis

According to a study published in Rheumatology, those at risk of rheumatoid arthritis who consume more omega-3 fatty acids can decrease their likelihood of developing the disease.*

Rheumatoid arthritis is a systemic inflammatory disease affecting multiple joints in the body. It usually manifests in the lining of the joints (synovial membrane) but can impact other organs. Patients with rheumatoid arthritis have a higher prevalence of cardiovascular disease than those without.

Researchers analyzed self-reported data about omega-3 consumption from 30 people who had autoantibodies for rheumatoid arthritis and 47 control patients who did not. Just 6.7% of the patients who had the autoantibodies reported taking an omega-3 supplement, compared with 34.4% in the control group. Blood tests also showed that those with the autoantibodies were “significantly more likely” to have lower levels of three essential omega-3 fatty acids than the control patients. Two of the crucial omega-3 fatty acids, DHA and EPA, may suppress a protein that regulates the intensity and duration of the immune response.

“There was a very substantial difference in the blood levels of omega-3 fatty acids between the people who took omega-3 supplements and those who did not,” said lead researcher Professor Jill Norris, PhD, of the Colorado School of Public Health.

Editor’s Note: This is the first study to find an association between omega-3 and the autoantibodies that lead to rheumatoid arthritis among patients who are at risk but have not yet developed the disease. Around 1.5 million Americans have rheumatoid arthritis. Women are 3 times more likely to develop it than men and prevalence appears to be increasing.

Reference

* Rheumatology. 2015, Sept 13.

Reduced Percentage of Deaths from Leading Causes over Several Decades

The October 27, 2015, issue of the Journal of the American Medical Association featured an article titled “Temporal Trends in Mortality in the United States, 1969-2013,” that documents a decline in the age-standardized death rate from five out of six leading causes of death, including heart disease, cancer, stroke, unintentional injuries, and diabetes.*

A temporal trend refers to the long-term—in this case, a 44-year period—trend regarding death rates. A systematic and comprehensive evaluation of long-term trends in mortality is important for health planning and priority setting and for identifying modifiable factors that may contribute to the trends.

A team from the American Cancer Society in Atlanta analyzed data from the US National Vital Statistics System (NVSS) of the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention for the years 1969 through 2013. During this time period, the age-standardized death rate per 100,000 individuals declined from 1,278.8 to 729.8 for all causes, which is a 42.9% reduction. Deaths from stroke declined by 77%, from heart disease by 67.5%, for unintentional injuries by 39.8%, from cancer by 17.9%, and from diabetes by 16.5%.

Editor’s Note: Despite these gains, deaths from chronic obstructive pulmonary disease (COPD) increased by 100%, although they began to decline during the last time point analyzed.

Reference

*JAMA. 2015 Oct 27;314(16):1731-39.

Vitamin E Delays Progression of Cellular Senescence

Vitamin E Delays Progression of Cellular Senescence

An article appearing in BioMed Research International reveals new findings concerning the antiaging properties of vitamin E. In an experiment involving two types of human cells, treatment with vitamin E resulted in a delay in cellular senescence in comparison with untreated cells.*

Senescent cells are those that have reached a state of irreversible growth arrest by attaining a limited number of divisions. According to authors Giorgio La Fata and colleagues, cellular senescence in vitro is related to the aging of organisms in vivo.

The team tested the effects of vitamin E in cultured human umbilical vein endothelial cells and human fibroblast cells. The researchers found an increase in the number of senescent cells over time in both types of cells. However, short-term vitamin E supplementation was associated with a reduction in the percentage of senescent cells in comparison with untreated control cells.

Editor’s Note: “An important contributor to the development of the senescence process is oxidative stress,” Dr. La Fata and co-authors note. “Oxidative stress usually occurs when the production or the exposure to reactive oxygen species (ROS) overwhelms the antioxidant systems of the cells. Vitamins E and C are important natural antioxidants capable of neutralizing the deleterious effects of reactive oxygen species.”

Reference

*BioMed Res Int . 2015.

Ashwagandha Associated with Improved Sexual Function in Females

An article in BioMed Research International reveals the outcome of a study that found improvements in sexual function among women who received a highly concentrated ashwagandha (Withania somnifera) root extract.*

The study included 50 women diagnosed with female sexual dysfunction, which included hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder, or combined genital and subjective arousal disorder. Twenty-five women received 300 mg ashwagandha twice per day with food and the remainder received a placebo for eight weeks. Sexual function (including desire, arousal, lubrication, orgasm, satisfaction, and pain), sexual distress, sexual activity, response to therapy, and tolerability of therapy were evaluated before treatment, and at four and eight weeks.

Women who received ashwagandha reported improved sexual function scores in the areas of arousal, lubrication, orgasm, and satisfaction. They also noted improvement in sexual distress and an increased number of successful sexual encounters by the end of the treatment period compared with the placebo.

Editor’s Note: As possible mechanisms, authors Swati Dongre and colleagues note that ashwagandha may reduce the effects of chronic stress (which interferes with sexual response) by lowering serum cortisol. Another possible mechanism is by “offsetting androgen deficiency syndrome, which is seen as contributing to a lack of sexual desire in some women” as suggested by the authors. In men, the herb has been shown to increase serum testosterone, which plays a role in sexual function in both genders.

Reference

*Biomed Res Int. 2015;2015:284154.

Magnesium Helps Prevent Amyloid Beta Aggregation in Experimental Research

Magnesium Helps Prevent Amyloid Beta Aggregation in Experimental Research

The December 2015 issue of The FASEB Journal reports the ability of ionic magnesium (Mg2+) to help reduce the deposition of amyloid beta in an Alzheimer’s disease mouse model.*

Pu Wang, PhD, of Northeastern University in Shenyang, China, and colleagues tested the effect of magnesium threonate, which is believed to penetrate the blood/brain barrier, on normal mice and mice that overexpressed a gene that increased amyloid beta production while decreasing the influx of magnesium into the brain. Among those that received magnesium, the researchers observed a reduction in amyloid beta aggregation and associated cognitive decline, accompanied by an elevation in brain levels of ionic magnesium.

“We hope that our findings will help improve clinical practice pertinent to the optimal administration of Mg2+ for delaying or even preventing the onset of Alzheimer’s disease,” commented Dr. Wang.

Editor’s Note: Dr. Wang and colleagues “also hope to extend our experimental models to other disorders such as severe craniocerebral injury, bronchial asthma, chronic pulmonary heart disease, arrhythmia, and myocardial necrosis, etc. and identify more targets of Mg2+ and strategies for treating these disorders.”

Reference

*FASEB J. 2015 Dec;29(12):5044-58.

Reduced Body Temperature Following Cardiac Arrest Associated with Survival

Reduced Body Temperature Following Cardiac Arrest Associated with Survival

An article published in Circulation reports better survival and neurologic outcome among cardiac arrest patients who underwent therapeutic hypothermia compared to standard treatment. Cardiac arrest occurs when the heart stops pumping, and can be caused by heart attack or other conditions.*

Researchers at the University of Colorado utilized data from 519 men and women enrolled in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry who survived cardiac arrest with nonshockable initial rhythms. Patients had experienced the return of spontaneous circulation and were comatose upon hospital admission. Subjects in the current study were treated with standard care or hypothermia, and were subsequently assessed for neurologic outcome.

The researchers, led by Sarah Perman, MD, uncovered a 2.8 times greater likeliness of survival to hospital discharge and a 3.5 times greater likeliness of better neurologic outcome among those treated with hypothermia in comparison with standard treatment. Life Extension Foundation funds a large hypothermia research project.

Editor’s Note: Nonshockable rhythms are defined as pulseless electrical activity and asystole, which are not treatable by defibrillation.

Reference

*Circulation. 2015 Nov 16.

New Research on Resveratrol

Sirtuin1 or simply SIRT1 is a gene involved in the regulation of cellular energy metabolism and functions as a cellular supervisor by preventing DNA damage and regulating gene transcription.1,2 It has been observed that calorie restriction, a validated method of extending mean and maximum life span, increases the activity of SIRT1.3

Due to its ability to enhance SIRT1,4-6 which is called the longevity enzyme, resveratrol has been extensively studied for its wide array of benefits. Through the activation of SIRT1, resveratrol favorably regulates many other genes.

In studies involving diabetic mice, resveratrol has been shown to improve insulin sensitivity by inhibiting the protein tyrosine phosphatase 1B (PTP1B) gene.7 This particular gene has been shown to be activated in diabetics and it wreaks havoc on insulin signaling pathways.8-11

Cells have a limited functional life span. Once a cell wears out, the ideal mechanism of removal is through a healthy process of programmed cell death called apoptosis. If the dysfunctional cell does not undergo apoptosis, it lingers and emits pro-inflammatory signals that lead to degenerative illnesses.12

Resveratrol can increase beneficial apoptosis to facilitate the healthy removal of decrepit cells.13 Resveratrol was shown to induce a critical cellular process called autophagy that removes waste (damaged proteins and organelles) from inside the cell.

In a recent study, rats were given the toxic chemotherapy drug doxorubicin (Adriamycin®). Resveratrol, along with calorie restriction, was shown to inhibit the damage done to the hearts of these rats by inducing autophagy resulting in improved cellular waste removal. There is growing evidence that compounds like resveratrol can shield against chemotherapy-induced cellular damage.14,15

Researchers have discovered a link between deactivation of SIRT1 and progeria, a condition that results in premature accelerated aging and markedly shortened life span.16,17 One study showed that mice with progeria given resveratrol had a 30% increase in median life span. The study also showed an increase in bone mineral density and a decline in potentially lethal atrophy.16

Scientists speculate that it would be interesting to test resveratrol on human progeria patients to see if it could slow the progression of this genetic disorder. Currently, there is no known cure and progeria patients typically die at about age 13.18

Neuronal function is dependent on the continuous removal of dysfunctional proteins and mitochondria. Increase activation of SIRT1 by resveratrol contri-butes to a process called autophagy (removal of cellular debris such as misfolded proteins and dysfunctional mitochondria).19,20

The accumulation of these cellular waste products has been shown to be involved in neurodegenerative diseases such as Alzheimer’s and Parkinson’s.21,22 Evidence also shows resveratrol decreases damage caused by cerebral ischemia, thus reducing the adverse effects caused by diminished blood flow to the brain that occurs with aging.23

In recent studies, resveratrol was shown to strengthen bone mass and inhibit bone demineralization. It does this by activating genes that signal our stem cells to turn into bone-forming cells called osteoblasts. In addition, resveratrol was shown in early studies to induce apoptosis (programmed cell death) of cells that break down bone, called osteoclasts, helping to preserve existing bone mass.24-26

Over 10.2 million older adults have been estimated to suffer from osteoporosis,27 and these recent findings suggest resveratrol can be used as a therapy to resist age-related bone loss.

—Chancellor Faloon

Reference
  1. Li X. SIRT1 and energy metabolism. Acta Biochimica et Biophysica Sinica. 2013;45(1):51-60.
  2. Kang H, Jung J-W, Kim MK, et al. CK2 Is the regulator of SIRT1 substrate-binding affinity, deacetylase activity and cellular response to DNA-damage. Bielinsky A-K, ed. PLoS ONE. 2009;4(8):e6611.
  3. Wang Y. Molecular Links between caloric restriction and Sir2/SIRT1 activation. Diabetes Metab J. 2014 Oct;38(5):321-9.
  4. Ghosh S, Liu B, Zhou Z. Resveratrol activates SIRT1 in a lamin A-dependent manner. Cell Cycle. 2013 Mar 15;12(6):872-6.
  5. Liu B, Zhou Z. Activation of SIRT1 by resveratrol requires lamin A. Aging. 2013 Feb;5(2):94-5.
  6. Lin CH, Lin CC, Ting WJ, et al. Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts. Age. 2014 Oct;36(5):9705.
  7. González-Rodríguez, Á., Santamaría, B., Mas-Gutierrez, et al. Resveratrol treatment restores peripheral insulin sensitivity in diabetic mice in a sirt1-independent manner. Mol Nutr Food Res. 2015 Aug;59(8):1431-42.
  8. Xu J, Li L, Qian Z, et al. Reduction of PTP1B by RNAi upregulates the activity of insulin controlled fatty acid synthase promoter. Biochem Biophys Res Commun. 2005 Apr 8;329(2):538-43.
  9. Zhang J, Li L, Li J, et al. Protein tyrosine phosphatase 1B impairs diabetic wound healing through vascular endothelial growth factor receptor 2 dephosphorylation. Arterioscler Thromb Vasc Biol. Jan 2015;35(1):163-74.
  10. Goldstein BJ. Protein-tyrosine phosphatase 1B (PTP1B): a novel therapeutic target for type 2 diabetes mellitus, obesity and related states of insulin resistance. Curr Drug Targets Immune Endocr Metabol Disord. 2001 Nov;1(3):265-75.
  11. Través PG, Pardo V, Pimentel-Santillana M, et al. Pivotal role of protein tyrosine phosphatase 1B (PTP1B) in the macrophage response to pro-inflammatory and anti-inflammatory challenge. Cell Death Dis. 2014;5(3):e1125.
  12. Childs BG, Baker DJ, Kirkland JL, Campisi J, van Deursen JM. Senescence and apoptosis: dueling or complementary cell fates? EMBO Rep. 2014 Nov;15(11): 1139-53.
  13. Delmas D, Solary E, Latruffe N. Resveratrol, a phytochemical inducer of multiple cell death pathways: apoptosis, autophagy and mitotic catastrophe. Curr Med Chem. 2011;18(8):1100-21.
  14. Dutta D, Xu J, Dirain MLS, Leeuwenburgh C. Calorie restriction combined with resveratrol induces autophagy and protects 26-month-old rat hearts from doxorubicin-induced toxicity. Free Radic Biol Med. 2014;74:252-62.
  15. Gu J, Hu W, Zhang, DD. Resveratrol, a polyphenol phytoalexin, protects against doxorubicin-induced cardiotoxicity. J Cell Mol Med. 2015 Jul 14.
  16. Liu B, Ghosh S, Yang X, et al. Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab. 2012 Dec 5;16(6):738-50.
  17. Ghosh S, Liu B, Zhou Z. Resveratrol activates SIRT1 in a Lamin A-dependent manner. Cell Cycle. 2013;12(6):872-6.
  18. Available at: www.mayoclinic.org/diseases-conditions/progeria/basics/definition/con-20029424. 5/3/2014. Accessed August 18, 2015.
  19. Ghavami S, Shojaei S, Yeganeh B, et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol. 2014 Jan;112:24-49.
  20. Wang R, Liu YY, Liu XY, et al. Resveratrol protects neurons and the myocardium by reducing oxidative stress and ameliorating mitochondria damage in a cerebral ischemia rat model. Cell Physiol Biochem. 2014;34(3):854-64.
  21. Funderburk SF, Marcellino BK, Yue Z. Cell “self-eating” (autophagy) mechanism in Alzheimer’s disease. Mt Sinai J Med. Jan-Feb 2010;77(1):59-68.
  22. Wu Y, Li X, Zhu JX, et al. Resveratrol-Activated AMPK/SIRT1/autophagy in cellular models of parkinson’s disease. Neuro-Signals. 2011;19(3):163-74.
  23. Raval AP, Lin HW, Dave KR, et al. Resveratrol and ischemic preconditioning in the brain. Curr Med Chem. 2008;15(15):1545-51.
  24. He X, Andersson G, Lindgren U, et al. Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production. Biochem Biophys Res Commun. 2010 Oct 22;401(3):356-62.
  25. Durbin SM1, Jackson JR, Ryan MJ, et al. Resveratrol supplementation preserves long bone mass, microstructure, and strength in hindlimb-suspended old male rats. J Bone Miner Metab. 2014 Jan;32(1):38-47.
  26. Tresguerres IF, Tamimi F, Eimar H, et al. Resveratrol as anti-aging therapy for age-related bone loss. Rejuvenation Res. 2014 Oct;17(5):439-45.
  27. Wright NC, Looker AC, Saag KG, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014 Nov;29(11):2520-6.