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.
Could using rapamycin be safer than not using it?
October 16, 2019. An opinion piece by Mikhail V. Blagosklonny of the Roswell Park Cancer Institute that appeared as the cover story of October 15, 2019 issue of Aging argues that the time is now to use the drug rapamycin to promote longer life.
Rapamycin, which is prescribed to organ transplant recipients to help prevent rejection, is an MTOR (mammalian target of rapamycin) inhibitor. mTOR is an enzyme that regulates cellular metabolism growth and proliferation. Research indicates that rapamycin and similar drugs may help suppress the emergence of aging-related diseases and extend lifespan.
“From the dawn of civilization, humanity has dreamed of immortality,” Dr Blagosklonny wrote. “So why didn’t the discovery of the anti-aging properties of mTOR inhibitors change the world forever? I will discuss several reasons, including fear of the actual and fictional side effects of rapamycin, everolimus and other clinically-approved drugs, arguing that no real side effects preclude their use as anti-aging drugs today.”
Other pharmaceuticals are already being used by some humans to potentially slow aging or the onset of aging-related diseases. The diabetes drug metformin, angiotensin-converting enzyme (ACE) inhibitors (which are used to treat high blood pressure), aspirin, and phosphodiesterase type 5 (PDE5) inhibitor drugs used to treat erectile dysfunction and other conditions, are examples of drugs currently used to prevent more than one disease associated with aging. Dr Blagosklonny argues that not using rapamycin may be more dangerous than smoking when one calculates potential years of lost life.
He admits that rapamycin is less effective at reversing aging than slowing it. For this reason, the drug can be administered before aging-related diseases make their appearance. Rather than self-medicating, people should have access to anti-aging clinics that assist in the implementation of an entire life extension regimen.
“The time is now,” he concluded.
Brain tissue kept alive for 25 days
October 14, 2019. Research reported recently in the journal Analytical Sciences found that brain tissue can be kept alive and functional for weeks via the use of a microfluidic device developed by researchers at the RIKEN Center for Biosystems Dynamics Research in Japan. The finding could aid researchers who use living tissue to evaluate the effects of individual drugs or combinations.
Keeping whole tissue alive for more than a few days has been challenging due to drying; however, immersion in a liquid culture medium can damage tissue due to inhibition of normal gas transfer. The new microfluidic device contains a semipermeable channel within an artificial membrane and solid walls made of a defoaming chemical known as PDMS. The device enables liquid culture medium to circulate and pass through the permeable membrane, thereby facilitating adequate gas exchange.
When tissue from the suprachiasmatic nucleus (which governs circadian rhythms) of mouse brains was stored in the device, it remained viable for 25 days, which is significantly longer than the viability associated with the use of other microfluidic culturing methods. In contrast, tissue stored in a conventional culture showed a decrease in neural activity of 6% after 10 hours.
"Controlling the medium flow was difficult because the microchannel that formed between the PDMS walls and the porous membrane was unusual,” commented first author Nobutoshi Ota. “However, we had success after trial and error modifications to the porous membrane and adjustments of the inlet/outlet flow rates."
Increased viability of stored whole tissue will benefit researchers who require the tissue for drug discovery and other purposes. "This method can be used for more than explanted tissues from animals," Dr Ota stated. "It will also improve research into organogenesis through long-term culturing and observation which is necessary for growing tissue and organs."
Research finding suggests metformin might help prevent ovarian cancer
October 11, 2019. An article published on October 9, 2019 in Clinical Cancer Research describes research designed to validate a hypothesis concerning the genesis of ovarian cancer.
“The ovarian cancer risk factors of age and ovulation are curious since ovarian cancer incidence increases in postmenopausal women, long after ovulations have ceased,” authors Curtis W. McCloskey, PhD, of Princess Margaret Cancer Centre and colleagues observe.
Acting on initial findings of age-associated ovarian fibrosis in mice, the researchers determined that fibrosis also occurred in the ovaries of postmenopausal women. "Fibrosis happens when body tissues are repeatedly injured and inflamed, leaving behind hard collagen fibers that pile up over time, like a scar on the skin," Dr McCloskey explained. "Cancer cells tend to like growing in these fibrotic tissues."
In the course of their research, an ovary from a 69-year-old woman was found to have no fibrosis. The woman had been using the diabetes drug metformin, which has been associated with a lower risk of ovarian cancer and other cancers.
The researchers hypothesized that ovarian fibrosis is caused by damage resulting from inflammation associated with ovulation. Giving mice a drug that prevents ovulation resulted in failure of the animals’ ovaries to become fibrotic during aging, adding evidence in support of the idea.
Subsequent examination of 27 ovaries removed from young and old women revealed no fibrosis among five that had been removed from postmenopausal women who used metformin. The findings suggest that metformin could help prevent ovarian cancer among those at risk.
"This study was about putting two and two together," commented senior author Barbara Vanderhyden, who is the Corinne Boyer Chair in Ovarian Cancer Research at the University of Ottawa. "Now we're doing more research to learn how fibrosis develops in the ovaries, and how metformin stops it from happening."
"Hit and run" reduces senolytic cells in humans
October 9, 2019. The September 2019 issue of EBioMedicine reported the results of a pilot study involving individuals with diabetic kidney disease who experienced a decrease in senescent cell burden following brief treatment with quercetin and the drug dasatinib.
Senescent cells are aged, damaged cells that, rather than self-destructing, survive to trigger inflammation and death in nonsenescent cells. While dasatinib plus quercetin has been the subject of experimental research that has demonstrated their antisenolytic effect, little clinical research has been conducted. “In the first clinical trial of senolytics, dasatinib plus quercetin improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans,” note James L. Kirkland and colleagues.
In young mice and humans, increased senescent cell abundance has been found in fat tissue in obesity-related conditions such as metabolic dysfunction and chronic kidney disease. For the current trial, nine participants with diabetic kidney disease received 100 milligrams dasatinib and 1,000 milligrams quercetin daily for three days. Eleven days later, participants exhibited a reduction in senescent cell markers and adipose tissue macrophages (white blood cells that are attracted and activated by senescent cells) in fat tissue. Skin markers of senescent cells and circulating senescent associated secretory phenotype factors were also reduced.
“We show for the first time that senolytic drugs decrease senescent cell abundance in humans,” the authors announced. “A three-day oral course of dasatinib plus quercetin in subjects with diabetic kidney disease reduced adipose tissue senescent cell burden 11 days later, as indicated by decreases in cells with markers of senescence. Thus, ‘hit-and-run’ treatment with senolytic agents, which in the case of dasatinib plus quercetin have elimination half-lives of less than 11 hours, is sufficient to decrease senescent cell burden in humans.”
Trial finds ashwagandha improves sleep
October 7, 2019. A randomized, double-blind, placebo-controlled trial reported on September 28, 2019 in Cureus resulted in better sleep and less anxiety (which can affect sleep) among individuals with insomnia who received an extract of the herb ashwagandha (Withania somnifera) in comparison with a placebo group.
The trial included 60 men and women aged 18 to 60 years with insomnia. Participants received 300 milligrams ashwagandha root extract or a placebo twice daily for ten weeks. Sleep actigraphy devices worn throughout the course of the trial monitored periods of rest and activity and provided data concerning sleep onset latency, total sleep time, waking after sleep onset and sleep efficiency. Subjects received physical examinations and were evaluated for other aspects of sleep as well as anxiety at the beginning of the study and at five and ten weeks.
At the end of the study, sleep onset latency was significantly less among participants who received ashwagandha in comparison with the placebo group. Sleep efficiency, sleep quality and other aspects of sleep also improved to a significantly greater extent in the ashwagandha group.
Anxiety, as evaluated by the Hamilton Anxiety Rating Scale, significantly decreased among participants treated with ashwagandha, resulting in lower values than those of the placebo group at the end of the trial.
“The present study is the first report in the direction of clinical research where the scientific clinical study is conducted to understand the effect of ashwagandha root extract on sleep quality in the considered patient population,” Deepak Langade of D.Y. Patil University School of Medicine and colleagues announce.
“Available conventional therapies of insomnia are known to develop drug dependency and exert side effects,” they note, adding that the herb “could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but needs further large-scale studies.”
Fruit flies live longer with treatment combination
October 4, 2019. An article that appeared on September 30, 2019 in the Proceedings of the National Academy of Sciences reports a life-extending effect in association with the intake of three compounds by fruit flies.
"As life expectancies increase, we are also seeing an increase of age-related diseases so there is an urgent need to find ways to improve health in old age," commented co-lead author, Jorge Castillo-Quan. "Here, by studying fruit flies which age much more rapidly than people, we have found that a combination drug treatment targeting different cellular processes may be an effective way to slow down the aging process."
Acting on previous research which found that the cancer drug trametinib, the immune system regulator rapamycin and lithium separately extended the lifespan of fruit flies, the team evaluated the effects of adding the compounds in combination as well as separately to fruit flies’ diets while additional flies served as controls. Each compound was associated with an increase in lifespan that averaged 11%, and the administration of two compounds extended lifespan by an average of 30%. Flies that received all three compounds experienced an even greater life extension benefit. "Previous studies in fruit flies have achieved lifespan extensions of about 5-20%, so we found it was quite remarkable that this drug combination enabled them to live 48% longer," Dr Castillo-Quan reported.
"There is a growing body of evidence that polypills - pills that combine low doses of multiple pharmaceutical products - could be effective as a medication to prevent age-related diseases, given the complex nature of the aging process,” stated principal investigator Linda Partridge. “This may be possible by combining the drugs we're investigating with other promising drugs, but there is a long way to go before we will be able to roll out effective treatments."
Vitamin C supplementation associated with improved survival among sepsis patients
October 2, 2019. The October 1, 2019 issue of the Journal of the American Medical Association published the results of a trial conducted at seven intensive care units which found a lower risk of mortality among men and women with sepsis who were treated with vitamin C.
Sepsis occurs when the immune system’s response to infection leads to damaging systemic inflammation, which can be life-threatening.
The investigation included 167 participants in the CITRIS-ALI trial, which evaluated organ dysfunction, inflammation and vascular injury following a 96-hour infusion of vitamin C or a placebo among individuals with sepsis and acute respiratory distress syndrome. "We conducted this phase II, proof-of-concept trial to explore if vitamin C is a more effective therapy for organ failure than the current standard of care for sepsis," stated lead researcher Alpha A. Fowler III, MD. "We did not find evidence that vitamin C improves sepsis-related organ failure in this particular trial, but it significantly reduced how long patients were hospitalized."
At 28 days, 25 of the 84 participants who received vitamin C had died, compared to 38 of the 82 participants who received a placebo. Compared to the placebo group, ventilator use averaged two and a half days less and time spent out of the ICU averaged three days more in the treated group. Twenty-five percent of those treated with vitamin C were transferred out of the ICU within a week in comparison with 12.5% of participants who received a placebo, and treated patients spent an average of six and a half more days out of the hospital.
"This therapy could potentially transform the way we care for sepsis patients,” Dr Fowler predicted. “We may have found a lifesaving therapy. While further research is needed, the results from our preliminary study are encouraging."