October 26 Research Roundup: New Cell Structures, Herpes and Alzheimer’s, Metformin Mechanism and How to Double Your Lifespan
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
New Structure Found in the Human Cell
Just when you think basic biology is completely known…. Researchers with the Karolinska Institute identified a new structure in human cells. The structure is a type of protein complex cells use to attach to their surroundings called reticular adhesions. The work was published in the journal Nature Cell Biology.
“It’s incredibly surprising that there’s a new cell structure left to discover in 2018,” stated principal investigator Staffan Stromblad, professor at the institute’s Department of Biosciences and Nutrition. “The existence of this type of adhesion complex has completely passed us by.”
Among the things it will help shed light on is how cells stay attached to the matrix during cell division. Other adhesion complexes dissolve during the process, which allows cells to divide, but this new complex doesn’t dissolve. They also control the ability of daughter cells to occupy the right position after cell division, a sort of “memory function.”
Herpes Linked to Alzheimer’s … Again
Researcher Ruth Itzhaki published a review paper in Frontiers in Ageing Neuroscience that looked at the sum of research over the last several decades linking the herpes virus that causes cold sores, Herpes Simplex Virus 1 (HSV1), to Alzheimer’s disease. “HSV1 could account for 50 percent or more of Alzheimer’s diseases cases,” Itzhaki, researcher at the University of Manchester, stated. “Our theory is that in APO-e4 carriers, reactivation is more frequent or more harmful in HSV1-infected brain cells, which as a result accumulate damage that culminates in development of Alzheimer’s.”
Herpes viruses live for our entire lives in our neurons and immune cells, reactivating and resurfacing in blisters when stressed, sick or our immune system is compromised. The question then has been, what if the infected neurons are in our brain during reactivation?
In Taiwan, 99.9 percent of the population is enrolled in a National Health Insurance Research Database. From 2017 to 2018, three studies were published describing data from the database on the development of senile dementia, which is often caused by Alzheimer’s. The research also linked the treatment of the patients with overt signs of infection with HSV or varicella zoster virus (VZV), which causes chickenpox.
“The striking results include evidence that the risk of senile dementia is much greater in those who are infected with HSV, and that anti-herpes antiviral treatment causes a dramatic decrease in a number of those subjects severely affected by HSV1 who later develop dementia,” Itzhaki stated.
Another possible mechanistic link is that viral DNA is located within plaques in post-mortem brain tissue from Alzheimer’s patients. The main proteins of both plaques and tangles also accumulate in HSV1-infected cell cultures, and antiviral drugs are able to prevent this accumulation. Itzhaki notes, “Considering that over 150 publications strongly support an HSV1 role in Alzheimer’s, these Taiwan findings greatly justify usage of antiherpes antivirals—which are safe and well-tolerated—to treat Alzheimer’s disease.”
Diabetes Drug Mechanism of Action ID’ed
The first-line drug of choice to treat type 2 diabetes is metformin. Up to now, the actual mechanism of how metformin affects liver glucose production wasn’t well understood, although it was believed to be transmitted via the mitochondrial respiratory chain. Researchers at the University of Helsinki have shown that metformin directly binds to the lipid phosphatase SHIP2, reducing its activity. This results in increased glucose uptake in muscle cells and decreased cell death in glomerular epithelial cells. Their research was published in The FASEB Journal.
“Our results indicate that the lipid phosphatase HSIP2 has a significant role in regulating glucose metabolism and cell death in podocytes,” stated Sanna Lehtonen at the University of Helsinki. “So, regulating SHIP2 activity with metformin or another suitable pharmaceutical agent is crucial in managing type 2 diabetes and particularly in preventing related diabetic kidney diseases.”
Identifying new mechanisms of action can potentially expand the drug’s indications outside diabetes, such as for cancer and cardiovascular diseases, and in regulation of aging. Also, a proposal has been made, which this study seems to support, that diabetes should be classified into five different subgroups, one of which would be severe insulin-resistant diabetes. This subgroup has a very high risk of also contracting diabetic kidney disease.
Cocktail of Drugs Can Double Lifespan … If You’re a Worm
Researchers at Yale-NUS College led by Jan Gruber identified a combination of drugs that doubles the lifespan of the worm Caenorhabditis elegans (C. elegans). The drug combo also delayed the rate of aging. Their research was published in Developmental Cell.
The research was to determine if healthy lifespan could be extended by using a cocktail of drugs that targeted different biochemical mechanisms related to lifespan. One example is the drug rapamycin, which is used after organ transplants to prevent immuno-rejection, but it has also been shown to extend the lifespan of C. elegans, fruit flies and mice. The team used combinations of two or three drugs that target different pathways.
“Many countries in the world, including Singapore, are facing problems related to aging populations,” Gruber stated. “If we can find a way to extend healthy lifespan and delay aging in people, we can counteract the detrimental effects of an aging population, providing countries not only medical and economic benefits, but also a better quality of life for their people.”
Possible New Approach to Prevent Prostate Cancer
A research team from NYU Langone Medical Center and School of Medicine and New York University published research in Nature Communications that described research that could lead to new prostate cancer drugs. The compounds, dubbed “cyclic peptoids,” decreased the growth of prostate cancer cells in cultures by 95 percent compared to untreated cells. It also blocked a key, related growth signal in tests on live animals.
“We designed our peptoids specifically to hit targets that are currently ‘undruggable,’ such as those causing treatment-resistant prostate cancer,” stated co-senior author Kent Kirschenbaum, professor in NYU’s Department of Chemistry.
The peptoids blocked cancer cell growth by interfering with the interaction between beta-catenin and T-cell factor (TCF) transcription factors, which are proteins that turn on genes that cause cells to multiply. The genes are necessary for early development of prostate tissue, but the gene activity is usually decreased in adulthood unless something causes it to reactivate, which can lead to cancer.
122,007 Exercisers Can’t Be Wrong—Cardiorespiratory Fitness Leads to Longer Life
The Cleveland Clinic conducted a retrospective study of 122,007 patients who participated in exercise treadmill testing between January 1, 1991 and December 31, 2014. They then evaluated all-cause mortality related to the benefits of exercise and fitness. The results were published in the Journal of the American Medical Association Network Open. The bottom line? Exercise helps you live longer.
“Aerobic fitness is something that most patients can control,” stated Wael Jaber, Cleveland Clinic cardiologist and senior author of the study. “And we found in our study there is no limit to how much exercise is too much. Everyone should be encouraged to achieve and maintain high fitness levels.”
In fact, the study found that the risk associated with poor cardiorespiratory fitness was comparable to—and in some cases was worse—than cardiovascular disease, diabetes and smoking.
The study broke participants into five performance groups—elite, high, above average, below average and low. Part of the goal was to determine if elite endurance athletes like ultra-marathon runners were overdoing it and hurting their health. What they found was that the survival benefits went up for the greater levels of cardiorespiratory fitness. And one figure was that in the patients over the age of 70, elite performers had an almost 30 percent reduced risk of mortality compared to high performers.
So it’s time to get some aerobic exercise.