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.
Taurine could improve MS therapies
December 11 2017. The addition of the amino acid taurine to current multiple sclerosis (MS) therapies could improve patient outcomes, according to research reported on November 13, 2017 in Nature Chemical Biology.
Multiple sclerosis develops when the immune system attacks the nerves’ protective myelin sheaths, which can lead to sensory deficits, loss of mobility and other symptoms.
Luke Lairson, PhD, and colleagues at The Scripps Research Institute (TSRI) investigated oligodendrocyte precursor cell differentiation, which is limited during progressive stages of demyelinating diseases such as MS. Oligodendrocytes are cells that produce the myelin sheath that insulates axons, which extend from nerve cells to transmit impulses to other nerve cells.
Using mass-spectrometry-based metabolomics, which can identify metabolites made in the body, taurine was found to be elevated more than 20-fold during oligodendrocyte differentiation and maturation. "Metabolomic profiling can offer unique insight into many different diseases, both mechanistically and therapeutically," noted co-senior author Gary Siuzdak, PhD, who is senior director of TSRI's Scripps Center for Metabolomics.
When added to cultured oligodendrocytes in combination with the pharmaceuticals benztropine or miconazole, taurine boosted oligodendrocyte precursor cell maturation. "Combining taurine with drugs that induce differentiation significantly enhances the process," reported Dr Lairson, who is an assistant professor of chemistry at TSRI. "You get more myelin."
"Remission of MS symptoms is dependent on the process of remyelination, so using taurine in combination with an existing MS drug and a future remyelination-inducing treatment may help patients by improving overall efficacy," he added. "This could be something to add to an MS therapeutic regime."
"Unlike other omic technologies, the beauty of metabolomics and activity testing is that metabolites are readily commercially accessible, generally inexpensive, and can directly impact phenotype quickly," Dr Siuzdak commented. "We are no longer passive observers but instead active participants."
Healthy mitochondria, healthy brain
December 8 2017. An article appearing on December 6, 2017 in Nature reports that improving mitochondrial defenses reduces the formation of amyloid plaques that are characteristic of Alzheimer’s disease. Mitochondria, the cells’ power plants, produce energy used by the body and brain. Unprotected mitochondria could increase the brain’s susceptibility to damage and the development of Alzheimer’s disease.
“Here we provide bioinformatic and experimental evidence of a conserved mitochondrial stress response signature present in diseases involving amyloid-beta proteotoxicity in human, mouse and Caenorhabditis elegans that involves the mitochondrial unfolded protein response and mitophagy pathways,” write Vincenzo Sorrentino and colleagues. “Using a worm model of amyloid-beta proteotoxicity, GMC101, we recapitulated mitochondrial features and confirmed that the induction of this mitochondrial stress response was essential for the maintenance of mitochondrial proteostasis and health.”
"These defense and recycle pathways of the mitochondria are essential in organisms, from the worm C. elegans all the way to humans," Dr Sorrentino explained. "So, we decided to pharmacologically activate them."
The researchers evaluated the antibiotic doxycycline and the vitamin nicotinamide riboside (NR), which can activate the mitochondrial unfolded protein response and mitophagy defense systems in a worm model of Alzheimer's disease. They observed improved health, performance and lifespan, and less amyloid plaque when the compounds were administered to the worms in comparison with untreated worms. Benefits were also found in human neuronal cells. When NR was tested in a mouse model of Alzheimer’s disease, mitochondrial and cognitive function improved, and plaque formation was reduced.
"So far, Alzheimer's disease has been considered to be mostly the consequence of the accumulation of amyloid plaques in the brain," senior author Johan Auwerx stated. "We have shown that restoring mitochondrial health reduces plaque formation - but, above all, it also improves brain function, which is the ultimate objective of all Alzheimer's researchers and patients."
“By targeting mitochondria, nicotinamide riboside and other molecules that stimulate their 'defense and recycle' systems could perhaps succeed where so many drugs, most of which aim to decrease amyloid plaque formation, have failed," Dr Sorrentino added.
Lithium shows promise for damage associated with fetal alcohol syndrome, stroke
December 6 2017. The January 15, 2018 issue of the journal Neuroscience reported that a dose of lithium blocked some of the effects alcohol, including disordered sleep, in a mouse model of fetal alcohol syndrome. While lithium has been used for decades in the treatment of bipolar disorder, it has been recently found to be associated with other benefits, including memory enhancement.
“Developmental ethanol exposure is a well-known cause of lifelong cognitive deficits, behavioral hyperactivity, emotional dysregulation, and more,” wrote M. Lewin and colleagues at New York University School of Medicine. “In healthy adults, sleep is thought to have a critical involvement in each of these processes. Our previous work has demonstrated that some aspects of cognitive impairment in adult mice exposed at postnatal day 7 to ethanol correlate with slow-wave sleep fragmentation.”
The team administered ethanol or saline to a group of mice on postnatal day 7 and gave half of the animals an injection of lithium chloride. In comparison with saline-treated controls, animals that received ethanol developed hyperactivity, cognitive impairment and reduced slow-wave sleep as adults; however, these effects were reduced by cotreatment with lithium. Lithium additionally prevented the development of changes in specific brain cells experienced by ethanol-treated mice.
"Our study showed that lithium chloride prevented many of the damaging neurological effects of alcohol abuse on the still-developing brain, especially the impact on the parts of the brain controlling sleep," stated co-senior investigator Donald Wilson, PhD.
Dr Wilson plans to investigate whether lithium chloride can block other forms of neurological damage, such as that which results from stroke and trauma. Co-lead investigator Monica Lewin, MS, remarked that the study brings researchers closer to determining whether the correction of fetal alcohol syndrome-associated sleep issues is key to preventing other developmental effects.
Youth drug mimetics discovered
December 4 2017.An article appearing on November 15, 2017 in the journal Aging announced the discovery of naturally occurring compounds that mimic the anticancer and antiaging effects of the prescription drugs metformin and rapamycin. Metformin is commonly used to treat type 2 diabetes and rapamycin is used by organ transplant recipients to prevent rejection.
“We applied several bioinformatic approaches and deep learning methods to the Library of Integrated Network‐based Cellular Signatures (LINCS) dataset to map the gene‐ and pathway‐level signatures of metformin and rapamycin and screen for matches among over 800 natural compounds,” explained Alexander Aliper of Insilico Medicine Inc, and colleagues. “We then predicted the safety of each compound with an ensemble of deep neural network classifiers.”
The analysis identified allantoin and ginsenoside (from ginseng) as mimetics of metformin, epigallocatechin gallate (which occurs in green tea) and isoliquiritigenin (found in licorice) as mimetics of rapamycin, and withaferin A (found in ashwagandha) as a strong mimetic of both compounds. They also identified four novel compounds as rapamycin mimetics.
"This study is significant not only for the identification of novel candidate mimetics of metformin and rapamycin, which as natural compounds are not subject to regulatory bodies like the FDA and which have higher-scoring safety profiles as indicated by our deep-learned safety profile classification analysis, but also for demonstrating particularly powerful screening methods that can be applied to the identification of novel and safe mimetics of other known anticancer and healthspan-extending drugs and compounds" commented coauthor Franco Cortese, who is Deputy Director of the Biogerontology Research Foundation.
"Aging is not recognized as a disease, so we need strong potential geroprotectors of natural origin on the market--supplements that slow down aging, affecting the key mechanisms of aging at the molecular and cellular level," coauthor Alexey Moskalev, PhD, added.
Schizophrenia associated with vitamin deficiencies from the start
December 1 2017. Findings from a meta-analysis reported on November 30, 2017 in Schizophrenia Bulletin reveal significantly lower levels of folate and vitamin D among individuals experiencing their first psychotic episode in comparison with control subjects.
Joseph Firth of NICM Health Research Institute at Western Sydney University in Australia and his colleagues analyzed 28 studies that examined blood levels of 6 vitamins and 10 minerals in 1,221 subjects who presented with first episode psychosis and 1,391 control subjects. They found significantly lower levels of the B vitamin folate and vitamin D in those with first episode psychosis compared to the controls. Rising levels of both vitamins were associated with decreases in symptoms. There was also limited evidence for an association between first episode psychosis and reductions in vitamin C.
"Although just one of many factors, it is important to recognize that nutritional deficiencies could certainly be contributing to the poor physical and mental health outcomes often observed in young people with psychosis," Dr Firth observed. "Our research has found vitamin D and folate deficiencies, previously observed in long-term schizophrenia, exist right from illness onset, and are associated with worse symptoms among young people with psychosis. Since both of these nutrients are vital for physical and psychological wellbeing, this finding emphasizes the importance of promoting a healthy diet for young people with psychosis, and potentially suggests adding targeted nutritional supplementation to standard treatment could improve recovery - although this theory has yet to be tested."
"While the results of our data analysis reveal that nutrient deficiencies are endemic in people suffering from first-episode psychosis, further work is needed to determine whether this is a by-product of the disorder, an effect from psychiatric medications, or whether lifestyle factors are to blame," senior author Jerome Sarris added.