New Research links childhood stress and psychiatric disease to premature cellular aging

A new study in Biological Psychiatry finds hallmarks of cellular aging in people who have experienced early life stress, depression, anxiety, or substance abuse. The relationship seen between psychopathology and shortened telomeres confirmed earlier reports, and this paper presents the first evidence of altered mitochondrial biogenesis, including increased mtDNA copy number, in people with early life stress, anxiety, or substance use disorders.

Background:Telomere shortening and alterations of mitochondrial biogenesis are involved in cellular aging. Childhood adversity is associated with telomere shortening, and several investigations have shown short telomeres in psychiatric disorders. Recent studies have examined whether mitochondria might be involved in neuropsychiatric conditions; findings are limited and no prior work has examined this in relation to stress exposure.

Methods: Two-hundred ninety healthy adults provided information on childhood parental loss and maltreatment and completed diagnostic interviews. Participants were categorized into four groups based upon the presence or absence of childhood adversity and the presence or absence of lifetime psychopathology (depressive, anxiety, and substance use disorders). Telomere length and mitochondrial DNA (mtDNA) copy number were measured from leukocyte DNA by quantitative polymerase chain reaction.

Results: Childhood adversity and lifetime psychopathology were each associated with shorter telomeres (p < .01) and higher mtDNA copy numbers (p < .001). Significantly higher mtDNA copy numbers and shorter telomeres were seen in individuals with major depression, depressive disorders, and anxiety disorders, as well as those with parental loss and childhood maltreatment. A history of substance disorders was also associated with significantly higher mtDNA copy numbers.

Conclusions: This study provides the first evidence of an alteration of mitochondrial biogenesis with early life stress and with anxiety and substance use disorders. We replicate prior work on telomere length and psychopathology and show that this effect is not secondary to medication use or comorbid medical illness. Finally, we show that early life stress and psychopathology are each associated with these markers of cellular aging.

Tyrka et al. Alterations of Mitochondrial DNA Copy Number and Telomere Length with Early Adversity and Psychopathology. Biological Psychiatry. Article in Press; Published Online: January 16, 2015. DOI:

A cure for glioma: nanoparticles deliver gene + pro-drug to brain

Biodegradable polymeric nanoparticles have the potential to be safer alternatives to viruses for gene delivery; however, their use has been limited by poor efficacy in vivo. In this work, we synthesize and characterize polymeric gene delivery nanoparticles and evaluate their efficacy for DNA delivery of herpes simplex virus type I thymidine kinase (HSVtk) combined with the prodrug ganciclovir (GCV) in a malignant glioma model. We investigated polymer structure for gene delivery in two rat glioma cell lines, 9L and F98, to discover nanoparticle formulations more effective than the leading commercial reagent Lipofectamine 2000. The lead polymer structure, poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-modified with 1-(3-aminopropyl)-4-methylpiperazine, is a poly(β-amino ester) (PBAE) and formed nanoparticles with HSVtk DNA that were 138 ± 4 nm in size and 13 ± 1 mV in zeta potential. These nanoparticles containing HSVtk DNA showed 100% cancer cell killing in vitro in the two glioma cell lines when combined with GCV exposure, while control nanoparticles encoding GFP maintained robust cell viability. For in vivo evaluation, tumor-bearing rats were treated with PBAE/HSVtk infusion via convection-enhanced delivery (CED) in combination with systemic administration of GCV. These treated animals showed a significant benefit in survival (p = 0.0012 vs control). Moreover, following a single CED infusion, labeled PBAE nanoparticles spread completely throughout the tumor. This study highlights a nanomedicine approach that is highly promising for the treatment of malignant glioma.

Abstract Image

Mangraviti et al. Polymeric Nanoparticles for Non-Viral Gene Therapy Extend Brain Tumor Survival In Vivo. ACS Nano. 2015 Feb 24;9(2):1236-49

8 Ways to Celebrate the Ultimate Pi Day: 3.14.15

Every year on March 14, math and science educators and enthusiasts across the globe celebrate the number that represents the ratio of circumference to diameter of a circle with parties, parades, pie eating and number memorization contests.

But this year, on March 14, 2015 (that’s 3-14-15) fans of this irrational number will get more Pi than ever before…and more than they’ll ever see again in their lifetime. That’s because the next two digits in the Pi sequence after 3.14 are 1, and 5.

After this year, we won’t see this many digits of Pi on our calendar again until the year 2115. Making this year’s Pi day the ultimate Pi day.

If you’re looking for fun and engaging ways to celebrate this once in a lifetime occurrence with your students while teaching them about the mystery and excitement of this special number, look no further.

We’ve gathered some of the most useful resources from around the web where you’ll find classroom activities, fun facts, teaching tools, and entire fan clubs dedicated to honoring Pi in all its forms.

From all of us at Ward’s Science, we wish you a happy Ultimate Pi Day, from our science lab to yours!

Here are Eight Ways to Celebrate

  1. See where Pi Day got its start
    The Exploratorium in San Francisco, CA is said to have founded the first Pi Day celebration over 22 years ago, and continues the tradition today with live events, activities, and contests all day long. Visit for a slew of Pi Day resources and schedule of events.
  2. Memorize one million digits of Pi
    Is your classroom up to the challenge? See how many digits you and your students can memorize and recite back without error – here are the first million digits to study. Think you can beat the current world record set by Chao Lu of China on November 20, 2005 for 67,890 digits in 24 hours and 4 minutes?
  3. Learn a Pi Day Rap Song
    Head to, a self-described one-stop Pi Day shop for teachers and number lovers, to get pumped up for your memorization competition with a Pi Day rap song set to the tune of Eminem’s “Lose Yourself”, along with more songs, Pi games, activities, and an entire community dedicated to sharing their love of Pi.
  4. Read the official National Pi Day Congressional Resolution
    On March 14, 2009, Congress voted in favor of a bill proposing Pi Day as a national holiday. See the full text of the U.S. House Resolution here.
  5. Study the History of Pi
    Learn more about the very first references to Pi in ancient history and texts, and study its chronology through the years.See the history here.
  6. Teach Pi with Storybook Characters
    Captivate student interest with medieval characters and timeless tales that present geometry concepts including Pi, shapes, circumference, and more. Shop titles like Sir Cumference and the Dragon of Pi, and more geometry books from Ward’s Science.
  7. Send a Pi Greeting Card
    There’s no better way to say “Happy Pi Day” from one math lover to another than with this selection of free and customizable online greeting cards.
  8. Don’t forget Einstein!
    Coincidentally, Albert Einstein, the father of modern physics, was born on Pi Day March 14, 1879. Learn more about the life of one of the most influential physicists and mathematicians of the 20th Century.

And if you want to go all out, consider timing your festivities for precisely 9:26 that day.

Gut Microbiota Are Related to Parkinson’s Disease

In Parkinson’s disease (PD), motor symptoms are mainly related to the loss of dopaminergic neurons in the substantia nigra. However, neuropathological changes are much more widespread, involving the autonomic nervous system, olfactory structures, lower brainstem, and cerebral cortex. Extranigral pathology is related to a broad spectrum of non-motor symptoms (NMS) that have been increasingly recognized as an important feature of PD. Gastrointestinal dysfunction, in particular constipation, affects up to 80% of PD patients and may precede the onset of motor symptoms by years. Idiopathic constipation is one of the strongest risk factors for PD. Prolonged intestinal transit time and constipation are associated with neurodegenerative changes in the enteric nervous system (ENS). These changes can be found in earliest stages of PD, sometimes years before motor symptoms appear, and therefore have been suggested as a premotor biomarker. Investigating whether high abundance of Prevotellaceae has protective effects against PD or whether low abundance is rather an indicator of disturbed mucosal barrier function will be important. Although very sensitive, low Prevotellaceae levels alone are not specific for PD. Inclusion of other bacterial families may increase accuracy, and further exploring the potential of fecal microbiome analysis as a biomarker for PD seems worthwhile. Further studies may elucidate the temporal and causal relationships between gut microbiota and PD and the mechanisms involved.

More elaborate study can be found at


How does gut bacteria maintain its stability during inflammation?

Pic:Bacteroides thetaiotaomicron gut bacteria. Source:

The human gut (intestine) has a dynamic ecosystem consisting of bacteria which can be either beneficial or harmful to the body. These microbial colonies are key to proper digestive functioning and it is noteworthy to understand how they have evolved to withstand bodily disruptions such as dietary changes, pathogens and toxin exposure.

The body responds to infection by activating its inflammatory mechanisms and by secreting molecules likeantimicrobial peptides (AMPs) which kill harmful bacteria. In spite of that, healthy gut microbial communities can resist AMPs and can remain stable for years in the gut.

The mechanism by which, these gut micro-organisms or microbiota can withstand high levels of inflammation-associated anti-microbial peptides (AMPs), was studied in a paper published in the journal ‘Science’. They studied a prominent gut commensal (a harmless co-existing bacteria), Bacteroides thetaiotaomicron which underwent a liposaccharide modification on its surface, allowing it to resist mammalian AMPs effectively.

Moreover, mass spectroscopy experiments revealed the presence of a specific phosphate group which alters the surface charge of the bacteria and neutralizes the negative charge of the cell, thereby decreasing antimicrobial binding. The protein responsible for this was identified as LpxF. Mutant bacteria in which this particular phosphate group was removed became more susceptible to AMP.

This gut microflora performs various useful functions for the host, such as fermenting unused energy substrates, preventing growth of harmful pathogenic bacteria and producing vitamins such as biotin and Vitamin K. A major factor in health is the balance of bacterial numbers; if the numbers are too high or low, it will result in harm to the host. Thus, understanding the mechanisms which are responsible for their stability is crucial, so that we can manipulate these communities for therapeutic purposes.

The original publication can be accessed here.

Food emulsifiers linked to metabolic syndrome and colitis!

Gut bacteria Picture courtesy:

Ever wondered about why the mayonnaise you bought at the market is so smooth and creamy, rather than a mixture of water and oily globules as it should be? How about ice cream or say, milk- Nature’s own product which consists of a complex mixture of fat droplets suspended in a solution. Yes, you are right! The consistency we see in most foods, is due to the presence of emulsifiers which mixes oil and water and makes stable emulsions. Nature uses proteins and phospholipids to cause emulsions, hence food industry contains a variety of emulsifiers modelled on these natural substances.

In a recent study published in the prestigious journal Nature, a group of researchers from Georgia State University Institute for Biomedical Sciences have shown that these emulsifiers can alter the gut microbiota composition and localization, thereby inducing intestinal inflammation which in turn promotes the development of inflammatory bowel disease like Crohn’s disease and metabolic syndrome.

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, affects millions of people and is often severe. Gut microbiota refers to the 100 trillion bacteria which resides in the intestinal tract and helps our body in the absorption of nutrients, production of vitamins and immunity. These diseases affect the gut microbiota and this research finding suggests that emulsifiers could be partially responsible for this disturbance and the increased incidence of these diseases.

“The dramatic increase in these diseases has occurred despite consistent human genetics, suggesting a pivotal role for an environmental factor,” says lead author Benoit Chassaing. “Food interacts intimately with the microbiota so we considered what modern additions to the food supply might possibly make gut bacteria more pro-inflammatory.”

They tested two commonly used emulsifiers such as polysorbate 80 and carboxymethylcellulose in mice, at doses which are reflective of the amount present in most processed foods.

They found that emulsifiers changed the species composition of gut microbiota and made it more pro-inflammatory. The altered microbiota had enhanced capacity to digest and infiltrate the thick mucus layer lining the intestine, which normally lacks bacteria. Due to the alteration in bacterial species, it resulted in more bacteria expressing flagellin and lipopolysaccharide, which triggered inflammation and activated the immune system.

In mice, which were genetically engineered to be susceptible to colitis- the altered bacterial profile caused the immune system to wreak havoc and caused chronic colitis. In mice with normal immune systems, emulsifiers induced mild intestinal inflammation which disturbed their microbiome. This made the normal mice eat more, which made them fatter and lead to metabolic syndrome.

None of these effects were seen in germ-free mice, indicating that the emulsifiers achieved them through their influence on the microbiome.

The team is now studying other emulsifiers and their effects on human beings. Even as the role of emulsifiers in metabolism and metabolic syndrome is being studied further, scientists warn against the tendency of excess food consumption.

“We do not disagree with the commonly held assumption that over-eating is a central cause of obesity and metabolic syndrome,” Andrew T. Gewirtz says. “Rather, our findings reinforce the concept suggested by earlier work that low-grade inflammation resulting from an altered microbiota can be an underlying cause of excess eating.”

Thus, emulsifiers may have contributed to the enormous increase in inflammatory bowel disease and metabolic syndrome that has occurred over the last half century. So, maybe we are not binge eaters after all. The altered microbiome caused by the emulsifiers is making us do it!

Source: Georgia State university

The original publication can be accessed here.

Vitamin D deficiency causes diabetes, not obesity

A new study has examined that people who have low levels of vitamin D are more likely to have diabetes, regardless of how much they weigh. The study conducted by the Endocrine Society found that people who have low levels of vitamin D are more likely to be obese and they also are more likely to have Type 2 diabetes, prediabetes and metabolic syndrome than people with normal vitamin D levels.

Vitamin D helps the body absorb calcium and maintain bone and muscle health. The skin naturally produces this vitamin after exposure to sunlight. People also absorb smaller amounts of the vitamin through foods, such as milk fortified with vitamin D. More than 1 billion people worldwide are estimated to have deficient levels of vitamin D due to limited sunshine exposure.

One of the study’s authors, Mercedes Clemente-Postigo, said that the major strength of this study was that it compares vitamin D levels in people at a wide range of weights while taking whether they had diabetes into account.

The cross-sectional study compared vitamin D biomarkers in 118 participants at the university hospital Virgen de la Victoria in Malaga as well as 30 participants from the Hospital Universitari Dr. Josep Trueta in Girona, Spain. All participants were classified by their body-mass index (BMI) as well as whether they had diabetes, prediabetes or no glycemic disorders. Researchers measured levels of vitamin D in the participants’ blood streams and vitamin D receptor gene expression in adipose tissue.

The analysis found that obese subjects who did not have glucose metabolism disorders had higher levels of vitamin D than diabetic subjects. Likewise, lean subjects with diabetes or another glucose metabolism disorder were more likely to have low levels of vitamin D. Vitamin D levels were directly correlated with glucose levels, but not with BMI.

Manuel Macas-Gonzalez, PhD, said that the study suggests that vitamin D deficiency and obesity interact synergistically to heighten the risk of diabetes and other metabolic disorders. The average person may be able to reduce their risk by maintaining a healthy diet and getting enough outdoor activity.

The study is published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism.