Fruit flies live longer with combination drug treatment

Fruit flies live longer with combination drug treatment

A triple drug combination has been used to extend the lifespan of fruit flies by 48% in a new study led by UCL and the Max Planck Institute for Biology of Ageing.

The three drugs are all already in use as medical treatments: lithium as a mood stabiliser, trametinib as a cancer treatment and rapamycin as an immune system regulator.

The findings, published in Proceedings of the National Academy of Sciences (PNAS), suggest that a combination drug treatment may one day be helpful at preventing age-related diseases in people.

"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," said the study's co-lead author, Dr Jorge Castillo-Quan, who began the research at the UCL Institute of Healthy Ageing before moving to Joslin Diabetes Center, Harvard Medical School.

"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 ageing process."

The researchers were building on previous studies finding that lithium, trametinib and rapamycin can each extend lifespan in fruit flies (Drosophila), which is supported by other preliminary evidence in mice, worms, and cells, and observational findings in people.

The three drugs all act on different cellular signalling pathways that together form the nutrient sensing network, which is conserved across evolution from worms and flies all the way to humans. This network adjusts what the body is doing in response to changes in nutrient levels. The three drugs in question act on different proteins of this network to slow the ageing process and delay the onset of age-related death.

For the latest study, the researchers gave fruit flies doses of lithium, trametinib and rapamycin, separately and in combination. Each drug individually extended lifespan by an average of 11%, while pairing two drugs extended lifespan by roughly 30%. When the three drugs were combined, the fruit flies lived 48% longer than flies in a control group that were not given the treatment.

"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 said.

The researchers found that in addition to acting on separate signalling pathways within the nutrient sensing network, the drugs also appear to complement each other to reduce side effects. Rapamycin has undesirable effects on fat metabolism, which can be similar to insulin resistance in people, but lithium appeared to cancel out this effect when the two drugs were given together.

The researchers will continue their research to better understand exactly how the drugs work in combination with each other, and hope to progress to experiments in more complex animals, such as mice, to gauge the effects on the entire body before eventually progressing to human trials.

Principal investigator, Professor Linda Partridge (UCL Institute of Health Ageing and Max Planck Institute for Biology of Ageing), said: "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 ageing process. 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."

"My research groups are working to understand the mechanism of the ageing process in order to find ways to help people stay healthy for longer. We are not trying to cheat death, but help people be healthy and disease-free in their final years," she said.

The study was funded by the Max Planck Society, American Federation for Aging Research, Glenn Foundation, National Institutes of Health, European Research Council, Research Into Ageing, Parkinson's UK, Wellcome and Academy of Medical Sciences and involved researchers in UCL Genetics, Evolution & Environment, UCL Queen Square Institute of Neurology, UCL Cancer Institute, Max Planck Institute for Biology of Ageing and Harvard University.

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Materials provided by University College London. Note: Content may be edited for style and length.

Online reviews reveal need for specialized drug treatment facility assessments

Almost 10 percent of the nation's entire population live with substance use disorder, but many struggle to find the right help -- a task which is made more difficult because there is no standardized rating system to ensure the quality of care within specialized drug treatment facilities. Even the efforts that do exist to evaluate these entities don't seem to be aligned with the central concerns of patients, according to a new study from Penn Medicine researchers which was published today in the Journal of General Internal Medicine.

Using a machine learning application, researchers uncovered the most common themes associated with facilities' reviews on Google and Yelp, then compared them to a survey run by the Substance Abuse and Mental Health Services Administration (SAMSHA) -- the most widespread evaluation method currently used for these facilities. However, that survey is intended to be an inventory of services provided and not patient satisfaction, so only 7 percent of its codes aligned themes from the patient reviews.

"It would be prudent of us to have a comprehensive method of defining quality, capturing data and adjusting care to be both meaningful and patient-centered at treatment facilities," said lead author Anish Agarwal, MD, an assistant professor of Emergency Medicine. "Without these considerations, we're attempting to tackle a component of the opioid epidemic without taking into account the voices of those who are actually seeking help."

Online reviews are considered to be unfiltered sources that come directly from patients and their support systems, a resource that the team, led by Agarwal and Raina Merchant, MD, the director of the Penn Medicine Center for Digital Health and an associate professor of Emergency Medicine, consider to be relatively untapped. The team analyzed 7,823 online reviews for 539 Pennsylvania facilities posted between the summers of 2010 and 2018. Both Yelp and Google use a five-star rating system, and the researchers found that 43 percent of the reviews fell into the five-star category, while another 34 percent were one-star, leaving just 23 percent for the middle ratings.

"We've seen this polarized trend more than once in online reviews involving patient satisfaction," said Agarwal. "People tend to be motivated to post a review if they feel that they had either a great -- or a terrible -- experience, and this usually manifests as either clicking one- or five-stars. We've seen a similar trend in online reviews of hospitals, emergency departments, and urgent care centers."

Almost 70 percent of the reviews were accompanied by text explaining the reviewers' thoughts. But reviews with text were significantly more likely to be lower rated (averaging 2.9 stars) than the ones without text (3.8 stars).

"People with strong opinions tend to want to share their experiences online. I imagine, the ones without text likely score higher because people have less of a strong opinion to voice," Agarwal explained. "When people leave a more negative review, like a one-star, they often want to follow it up with a 'why.' This is very helpful to researchers like us because we can begin to understand more about the person's experience and why it may have been subpar, and then we can take steps to address it."

To dig into the text of the online reviews, the researchers fed the review text into an automated machine learning tool to identify and group instances of the same words across reviews. They then applied a technique known as Differential Language Analysis to pull out themes that correlated to certain online reviews. When it came to five-star reviews, there was a correlation with mentions of a focus on recovery, staff helpfulness, compassionate care, experiencing a "life-changing moment," and general professionalism. However, the themes most directly tied to one-star reviews included long wait times, poor accommodations, poor phone communication, the types of medications offered, and appointment availability.

The researchers identified three of the 14 services categories in the SAMSHA survey that aligned with the top themes derived from patients' online reviews. Moreover, 12 of the service codes from the survey, out of 162, total, addressed top themes from online. Seeing the differences between the survey and what patients post about provides a new source of information to help guide quality improvement within these centers.

Moving forward, Agarwal, Merchant and their fellow researchers hope that their discoveries can help build the yard stick by which drug treatment facilities are measured to better reflect the actual feelings of those living with substance use disorder.

"Future work will focus on evaluating reviews across the United States and use this to collaborate with organizations creating national quality measures that encompass patient feedback and other performance measures," Merchant said. "We would also like to work with online review platforms to add targeted questions to these portals that seem most important to patients and caregivers."

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Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.

Who is left behind in Mass Drug Administration?

Ensuring equity in the prevention of neglected tropical diseases (NTDs) is critical to reach NTD elimination goals as well as to inform Universal Health Coverage (UHC). Now, researchers reporting in PLOS Neglected Tropical Diseases have unmasked inequities in the delivery of Mass Drug Administration (MDA) programmes that leave vulnerable populations underserved.

Individuals and communities affected by NTDs are often the poorest and most marginalized. NTDs amenable to prevention through MDA programmes have been described as the "litmus test" for UHC due to the high MDA coverage rates needed to be effective and their model of community engagement for access and acceptance of medicines.

In the new work, Laura Dean of Liverpool School of Tropical Medicine, UK, and colleagues analyzed MDA programmes across Cameroon, Ghana, Liberia and Nigeria. They used both qualitative programmatic analysis and gendered intersectional theory -- which provides a framework for how power and position shape people's experiences -- to interrogate the domains of coverage within the Tanahashi Framework; availability, accessibility, acceptability, contact and effectiveness of programmes.

The team found effective treatment for individuals and communities is shaped by individual identities and the intersecting axes of inequity that converge to shape these positions, including gender, age, disability and geography. Health systems bottlenecks, challenges and limitations, sometimes due to lack of consideration and discussion of gender and equity issues have left vulnerable populations underserved in relation to the prevention and treatment of PC NTDs across all types of coverage explored within the Tanahashi framework.

"As we move toward the progressive realization of UHC, these findings should be central to discussions on providing health for all," the researchers say. "MDA campaigns have been implemented for many years and the inequities within them are only now being discussed."

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Materials provided by PLOS. Note: Content may be edited for style and length.