Mind-body practices lower blood sugar levels in people with type 2 diabetes

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Mind-body practices lower blood sugar levels in people with type 2 diabetes

New research from the Keck School of Medicine of USC reveals mind-body practices are highly effective at reducing blood sugar levels in people with type 2 diabetes
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Mind-body practices such as yoga and meditation are increasingly popular tools for promoting health and combating diseases, including type 2 diabetes. Approximately 66% of Americans with type 2 diabetes use mind-body practices and many do so because they believe it helps control their blood sugar. Until now, however, whether mind-practices can reduce blood glucose levels has never been rigorously quantified.
According to new research conducted by a team from the Keck School of Medicine of USC, published recently in the Journal of Integrative and Complementary Medicine, some mind-body practices can be nearly as effective as commonly prescribed drugs at reducing blood glucose levels in people with type 2 diabetes.
“The most surprising finding was the magnitude of the benefit these practices provide,” said Fatimata Sanogo, a PhD student in the Department of Population and Public Health Sciences and lead author of the study. “We expected there to be a benefit, but never anticipated it would be this large.”
All practices achieve significant reductions in blood sugar levels
The team analyzed data from randomized controlled trials conducted across the globe between 1993 and 2022. They found 28 trials in which people with type 2 diabetes began a mind-body practice in addition to receiving medication and compared their results with people who only received medication to reduce their blood sugar levels.
This study, the first to analyze a range of mind-body practices including meditation, qigong, yoga and mindfulness-based stress reduction and their effect on blood glucose levels, revealed that all mind-body practices led to significant reductions in blood sugar levels.
Taken as a whole, the mind-body practices averaged a .84% reduction in hemoglobin A1c, a measure of the average blood glucose level for the past 3 months. Yoga, the most-studied modality, provided the largest benefit, about a 1% reduction in hemoglobin A1c. The authors noted that a 1% reduction is particularly notable because metformin, the most prescribed diabetes drug, reduces hemoglobin A1c in people with type 2 diabetes by 1.1% on average.
“What is important about this study is that the effect is very strong and that it is on top of the standard of care,” said Richard M. Watanabe, PhD, professor of population and public health sciences and physiology and neuroscience at the Keck School of Medicine, noting that the research revealed that mind-body practices helped participants achieve reductions in blood glucose levels on top of the reductions they were getting from medication.

A potential new tool for clinicians

The research suggests that mind-body practices could be used as a both as a complementary nonpharmacological treatment for people with type 2 diabetes and possibly as a preventive measure as well.
New effective methods for keeping type 2 diabetes under control are needed, since only about half of people with type 2 diabetes succeed at reducing their blood sugar levels to the target level of 7% hemoglobin A1c. At the same time, the number of Americans who are pre-diabetic has grown to about one-third in recent decades.
The studies came from different countries, further suggesting that mind-body practices could benefit people with type 2 diabetes worldwide.

“This could be an important tool for many people because type 2 diabetes is a major chronic health problem and we are not doing a good enough job at controlling it,” said Sanogo. “Although this study does not address it as a preventive measure, it does suggest it could help people who are pre-diabetic reduce their risk for future type 2 diabetes.”

About the study

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Exposure to air pollution worsens COVID-19 outcomes, even among the fully vaccinated

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COVID-19 is a respiratory illness, so it’s not surprising that exposure to poor air quality worsens patient outcomes. But how does air pollution affect people who are vaccinated?

To answer that question, a team of researchers analyzed data from more than 50,000 COVID-19 patients across Southern California. By comparing publicly available air quality monitoring data with deidentified patient medical records, they first established that regardless of air pollution exposure, vaccines go a long way in reducing COVID-19 hospitalizations.

“Fully vaccinated people had almost 90% reduced risk of COVID hospitalization, and even partially vaccinated people had about 50% less risk,” said Zhanghua Chen, PhD, assistant professor of population and public health sciences at the Keck School of Medicine of USC and co-first author of the study.

But air pollutants–in particular fine particles (PM2.5) and nitrogen dioxide (NO2)–are still harmful. Even among people who were vaccinated, exposure to those two pollutants over the short or long term increased the risk of hospitalization up to 30%.

“Among vaccinated people, the detrimental effect of air pollution exposure is a little smaller, compared to people who were not vaccinated,” Chen said. “But that difference is not statistically significant.”

The study was just published in the American Journal of Respiratory and Critical Care Medicine. The research builds on the team’s earlier findings, which helped establish the link between air pollution exposure and COVID-19 severity.

“These findings are important because they show that, while COVID-19 vaccines are successful at reducing the risk of hospitalization, people who are vaccinated and exposed to polluted air are still at increased risk for worse outcomes than vaccinated people not exposed to air pollution,” said corresponding author Anny Xiang, PhD, MS, a senior research scientist at Kaiser Permanente Southern California’s (KPSC) Department of Research & Evaluation.

Short-term and long-term exposures

The researchers analyzed medical records, which were deidentified to protect patient privacy, from KPSC patients. Across the health care network, 50,010 patients, ages 12 and up, were diagnosed with COVID-19 in July or August of 2021, when the Delta variant was circulating and many people had been vaccinated.

Then, the researchers calculated estimated air pollution exposure levels for each participant based on residential addresses. They looked at average PM2.5, NO2, and ozone (O3) levels during the one-month and one-year periods before each patient received a COVID-19 diagnosis.

“We investigated both long-term and short-term air pollution exposure, which may influence COVID-19 severity through different mechanisms,” said Chen.

Over the long term, pollution is linked to increases in cardiovascular and lung diseases, which are in turn linked to more severe COVID-19 symptoms. In the short term, air pollution exposure may worsen inflammation in the lungs and could even alter the immune response to the virus.

Chen, Xiang, and their colleagues found that among 30,912 people who were unvaccinated, high short-term PM2.5 exposure increased the risk of COVID-19 hospitalizations by 13%, while long-term exposure increased the risk by 24%. For NO2, short-term exposure raised hospitalization risk by 14% and long-term exposure raised the risk by 22%. The pollutant O3 was not significantly associated with COVID-19 hospitalizations.

For those who were partially or fully vaccinated, the hospitalization risks related to air pollution exposure were slightly lower–but the difference was not statistically significant.

Using data from medical records and neighborhood-level databases, the researchers were able to control for the effects of vaccination status, age, sex, race/ethnicity, health insurance status, body mass index, smoking history, health comorbidities, education level, income level and population density.

Improving indoor air quality

The findings suggest that in order to reduce severe cases of COVID-19, we need to improve air quality. This spring, the Biden Administration launched the Clean Air in Buildings Challenge, an effort to install high-efficiency particulate absorbing (HEPA) filters in schools and other public buildings.

Chen recently received funding to conduct clinical trials of HEPA filters to determine whether they reduce the risk of diabetes and cardiovascular disease. Her team will also continue their collaboration with KPSC to study the direct impacts of indoor air purifiers on COVID-19 patients.

About this study

In addition to Chen and Xiang, the study’s other authors are Brian Z. Huang and Frank D. Gilliland of the Department of Preventive Medicine, Keck School of Medicine of USC; Margo A. Sidell, Ting Chow and Mayra P. Martinez of the Department of Research & Evaluation, Kaiser Permanente Southern California; and Fred Lurmann of Sonoma Technology, Inc.

This work was supported by the National Institute of Environmental Health Sciences at the National Institutes of Health [3R01ES029963-01] and the Keck School of Medicine of USC’s Department of Preventive Medicine COVID-19 Pandemic Research Center (CPRC).

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Keck Hospital of USC named top performer by leading heath care performance improvement compapy

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LOS ANGELES – Keck Hospital of USC has been recognized as a top performer in the 2022 Bernard A. Birnbaum, MD, Quality Leadership Ranking by Vizient, Inc., a leading health care performance improvement company.
The designation acknowledges the hospital’s excellence in delivering high-quality care based on the annual Vizient Quality and Accountability Study.
Keck Hospital ranked No. 11 out of 107 comprehensive academic medical centers nationally and achieved a five-star rating, the highest possible.
“The hospital is committed to providing best possible outcomes for our patients, and this honor is a reflection of our continued dedication,” said Stephanie Hall, MD, MHA, chief medical officer of Keck Medical Center of USC, which includes Keck Hospital and USC Norris Cancer Hospital.
The Vizient rankings evaluate performance on the quality of patient care in six domains: safety, mortality, effectiveness, efficiency, patient centeredness and equity. They factor in data from Vizient as well as the Centers for Disease Control and Prevention and a national survey of patients’ perspectives of hospital care known as the Hospital Consumer Assessment of Healthcare Providers and Systems survey.
“This recognition is one of several safety and quality distinctions the medical center has recently received and is a further testament to the hard work of our entire staff,” said Marty Sargeant, MBA, CEO of Keck Medical Center.
Earlier this year, Keck Hospital earned an “A” Hospital Safety Grade for the sixth consecutive time from The Leapfrog Group, an independent national watchdog organization, for achieving the highest national standards in patient safety. In 2021, The Leapfrog group named USC Norris Cancer Hospital a Top Teaching Hospital for outstanding quality and safety.
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Dad brain is real: Study reveals men’s brains change after baby arrives

Psychologist Darby Saxbe leads the Center for the Changing Family and a research effort to explore how parents change biologicially and neurobiologically in response to their babies — all at the USC Dornsife College of Letters, Arts and Sciences.

Saxbe, an associate professor, recently had a study published in the journal Cerebral Cortex and found evidence that men develop a sort of “dad brain” after their baby is born, somewhat like how mothers’ brains change in response to their newborns. She discussed why studying these changes in parents is important and what she hopes to tackle next.

Why are you studying these changes in the parents’ brains? What do you hope to understand?

Parenting is incredibly important for society and public health, but also understudied from a neurobiological perspective. We’re hoping our research can inform public policies like paid family leave and other initiatives that support new parents.

What is neuroplasticity and what does it usually signify? Why would it change when one becomes a parent?

We’re still learning about neuroplasticity, but there is evidence that the brain changes and grows when we develop a new skill, like learning a musical instrument, or during developmental windows like early childhood and adolescence. Becoming a parent entails changes to your lifestyle and your biology and requires new skills like being able to empathize with a nonverbal infant, so it makes sense — but has not been proven — that the brain would be particularly plastic during the transition to parenthood as well.

What is the “parental caregiving brain network”? Does this exist for mothers, too?

Yes — it does exist for mothers — this refers to areas of the brain that have been shown to be involved in parenting or caregiving (and pregnancy and lactation) in both human and animal studies.

The study shows that you found changes in the default mode network. What is this network and what do these changes mean for men who are new fathers? What does it mean for their partners?

The default mode network refers to the regions of the brain that “light up” when the brain is at rest (not doing a particularly cognitive task). These regions are thought to be involved in mentalizing about other people’s thoughts and feelings. The fact that we found changes in that part of the brain both for fathers and mothers suggests that there is some remodeling of the social brain taking place.

You note that these changes are occurring in the cortex. What is the cortex responsible for, particularly as it relates to parenting?

The cortex is the latest-evolving part of the brain that is involved in attention, planning, and executive functioning and is more unique to humans. The subcortical regions (below the cortex) are the more basic brain structures that you see in animals, involved in reward, threat, and salience detection. In moms we see both subcortical and cortical changes … in dads we just saw cortical changes. It’s too soon to speculate with such a small sample but it might suggest more higher-order processing involved in fatherhood specifically.

Noted in here, too, is that volumes in the men’s visual network decreased. Do you have any hypotheses on the reasons that would drive changes in the visual system?

We’re not sure, although it may be that visual cues are particularly important for orienting to offspring and understanding their needs, given that infants are non-verbal.

Based on your results, what do you want to explore next?

We plan to study individual differences in fathers’ brain changes that are associated with hormones and parenting.

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Next-generation liquid biopsy detects nano-sized signs of breast cancer in early-stage patients

A USC-led team of scientists has found indications that a special blood test called a liquid biopsy could determine whether a patient has breast cancer at its early stage and if that cancer is unlikely to return.

The high-definition comprehensive liquid biopsies are conducted using a standard blood draw from the arm of a patient in a doctor’s office. Once in the laboratory, the sample is examined for signs of cancer.

The study demonstrating the liquid biopsy results for early breast cancer detection was published on Sept. 27 in Nature’s npj Breast Cancer journal. The work was a collaboration between USC, Billings Clinic, Duke University, Epic Sciences and the USC Norris Comprehensive Cancer Center. The results raise hopes that one day doctors could detect breast cancer in patients with a simple blood draw.

The researchers at the USC Michelson Convergent Science Institute in Cancer (CSI-Cancer) are cautiously optimistic about their findings. They are eager to test and see whether the results will be proven in larger clinical trials to demonstrate the benefit of the method for patients everywhere.

It’s an amazing opportunity to change how early breast cancer detection is being done with a simple blood draw.

Peter Kuhn, USC’s CSI-Cancer

“It’s an amazing opportunity to change how early breast cancer detection is being done with a simple blood draw, but it’s only a research outcome at this point and we still need to demonstrate clinical benefit,” said Peter Kuhn, a USC cancer physicist who directs CSI-Cancer.

Breast cancer is the most prevalent form of cancer in the world, affecting 1 in 8 women over their lifetime.

Since 1976 when the American Cancer Society endorsed mammography X-rays, the technique — along with a tissue biopsy — has become the standard way for doctors to check patients for breast cancer.

Breast cancer detection: Mammography isn’t 100% accurate

But mammography is not 100% accurate and its detection can be impeded by healthy dense tissue. Mammography’s sensitivity to breast cancer is about 87%, according to the Breast Cancer Surveillance Consortium. And for some women, mammograms are not accessible, especially those living in poor isolated communities that have no clinics or hospitals. Other women simply do not get a regular mammogram.

But a tissue biopsy also is not a foolproof method. Although it can reveal information about the tumor, it has limitations. Doctors can sample only a small area and may fail to capture the full extent of the tumor. A tissue biopsy is also invasive and painful.

Combined, the drawbacks for diagnosis with mammograms and tissue biopsies mean some patients are not diagnosed until the cancer has grown and spread. New methodologies such as CSI-Cancer’s liquid biopsy can bring a complementary toolset into clinical practice.

For the study, Kuhn and his team worked with 100 breast cancer patients — some early and some late stage — and 40 patients without breast cancer from April 2013 through January 2017. The work was conducted at clinical sites including at the USC Norris cancer center at the Keck School of Medicine of USC; the Billings Clinic in Montana; the Duke University Cancer Institute in Durham, N.C.; and the City of Hope Comprehensive Cancer Center in Duarte.

The team tested a theory that the high-definition liquid biopsy could detect multiple cancer biomarkers, including the so-called “oncosomes” — nano-sized, membraned cargo carriers that enrich the body’s environment for cancer growth. These oncosomes are secreted by cancer cells as the group has shown previously.

“The news here is that we found the vast majority of early-stage breast cancer patients have these oncosomes at very robust levels,” said Kuhn, a Dean’s Professor at the USC Dornsife College of Letters, Arts and Sciences and cancer physicist. “They’re about 5-10 microns in diameter, about the size of a cell. We first identified these large vesicles in prostate cancer about a year-and-a-half ago and showed that they are related to the cancer. They are hiding in plain sight.”

A future diagnostic tool for breast cancer detection?

If further studies produce similar results, it could mean that the next generation high-definition liquid biopsy may become a diagnostic tool for early breast cancer detection and other cancers, he said. The test also could inform patients who have been treated for cancer that they will most likely remain cancer-free.

“Typically, I’m the bearer of bad news. I say, ‘You have cancer in your blood,'” Kuhn said. “But a test like this could give hope that if there is a sign of cancer, we can find it very early and improve treatment and survival.”


Kuhn’s co-authors included from USC: Sonia Maryam Setayesh, Olivia Hart, Amin Naghdloo and Nikki Higa, Anand Kolatkar, as well as Nicholas Matsumoto, Rafael Nevarez, James B. Hicks, Jeremy Mason, Stephanie N. Shishido at USC Michelson. Other researchers were Jorge Nieva and Janice Lu of the USC Norris Center at Keck Medicine of USC, Shelley Hwang of Duke University School of Medicine, Kathy Wilkinson and Michael Kidd of Billings Clinic, as well as Amanda Anderson of Epic Sciences in San Diego.

The study was funded by grants from Breast Cancer Research Foundation; USC Norris Comprehensive Cancer Center; the National Cancer Institute; National Institutes of Health; Kalayil and Leela Chacko, Fellowship; Winnie and James Hart Endowed Fellowship; USC Dornsife Student Opportunities for Academic Research Fellowship; Vassiliadis Research Fund; Vicky Joseph Research Fund; Hart Family Research Fund; The Hsieh Family Foundation; Sandy Borden Thielicke; Jennifer B. and Gregory A. Ezring; Rochika and Kenny Dewan; Andy Perlman; Neil and Anjini Desai; Mamak and Mahmood Razavi Research Fund; Susan Pekarovics; Anila P. Bhagavatula; Giorgio De Santis; Thuy Thanh Truong; Cheryl Faillace; Wayne R. Green Fund; Armstrong McDonald Foundation; Ms. Margaret Turney Hulter Funds; Suzanne B. Borden Fund; and Mr. and Mrs. Stanley A. Mayer Fund.

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Low-calorie sugar substitute consumption during adolescence appears to impair memory later in life

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Scientists using laboratory models find that eating FDA-approved levels of saccharin, ACE-K and stevia early in life may result in several changes to the body, including brain regions involved in memory and reward-motivated behavior.

By Darrin S. Joy – September 28, 2022

Diet soft drinks often use low-calorie sugar substitutes such as stevia and acesulfame potassium, or Ace-K. (Image Source: iStock.)
Diet soft drinks often use low-calorie sugar substitutes such as stevia and acesulfame potassium, or Ace-K. (Image Source: iStock.)
A high-sugar diet early in life has been shown to harm brain function, but what about low-calorie sugar substitutes? A new study reveals they may take a heavy toll on the developing brain and gut.

The News: In a study published Sept. 13 online in the journal JCI Insight, scientists at the USC Dornsife College of Letters, Arts and Sciences show that adolescent rats that consumed the low-calorie sweeteners saccharin, ACE-K and stevia exhibited long-term impairments in memory.

The findings align with those from earlier studies in which the researchers show that adolescent rats that consume sugar suffer lingering memory impairment.
Consuming low-calorie sweeteners also affected metabolic signaling in the body, which can lead to diabetes and other metabolism-related diseases.
Rats that consumed low-calorie sweeteners as adolescents were less willing to work for sugar as adults, but they consumed more sugar if it was freely available, another factor that might affect the likelihood of developing metabolic disease.
Why It Matters: Advice on what to eat and when to eat it varies widely. Findings from studies like this can help consumers and clinicians make healthier choices throughout the lifespan, say the researchers.

“While our findings do not necessarily indicate that someone should not consume low-calorie sweeteners in general, they do highlight that habitual low-calorie sweetener consumption during early life may have unintended, long-lasting impacts,” said Scott Kanoski, associate professor of biological sciences at USC Dornsife.

What It Means for Humans: While most studies of low-calorie sweeteners focus on one substance and use amounts far exceeding the norm, the researchers made sure the study was in line with real-life conditions for people.

Sweeteners tested include saccharin, acesulfame potassium (ACE-K) and stevia — which are commonly used in sweetened foods.
The amount of sweetener consumed fell within FDA-approved guidelines for humans.
In Their Words:

“Research using rodent models and low-calorie sweeteners has typically involved consumption levels that far exceed the FDA ‘acceptable daily intake’ (ADI) levels and used only a single sweetener. To design our research to be more applicable to humans, we kept consumption levels within the ADI and used multiple low-calorie sweeteners to determine if effects were specific to a given sweetener or general across sweeteners.”

— Lindsey Schier, Gabilan Assistant Professor of Biological Sciences at USC Dornsife

The Experiment: To determine the effect of low-calorie sweetener consumption on memory, the researchers used methods that test object recognition and spatial recognition.

Rats were provided water sweetened with either stevia, ACE-K or saccharin or plain water, along with their normal food.
After a month, the rats’ memory was tested using two different methods — one tests if they remember an object they’ve seen before and the other is a maze.
In the end, rats consuming sweetener were less likely to remember an object or the path through the maze than those that drank only plain water.

What Else?

The scientists also found other effects among the rats after they consumed sweeteners.

They had fewer receptors on their tongues that detect sweet taste.
The biological mechanism in their intestines that transports glucose into the blood was altered.
Their brains had changed, specifically in regions associated with memory control and reward-motivated behavior.
What’s Next?

Kanoski and Schier say the findings reveal more questions worth exploring, including:

How do sweetener substitutes cause a reduction in sweet taste receptors and how does that affect later dietary behavior?
What does the change in the nutrient transport in the gut mean for health?
What biological mechanisms link sweetener consumption with the changes to the brain?
The researchers say they intend to explore ways to reverse the long-lasting effects of adolescent low-calorie sweetener consumption and to study how it influences food choices and preferences later in life.

About the Study

In addition to Schier and Kanoski, authors on the study include Linda Tsan, Sandrine Chometton, Anna Hayes, Molly Klug, Lana Bridi and Rae Lan of USC Dornsife; Yanning Zuo and Xia Yang of UCLA; Shan Sun and Anthony Fodor of the University of North Carolina at Charlotte; and Emily Noble of the University of Georgia.

The study was supported by National Institute of Diabetes and Digestive and Kidney Diseases grants DK123423 and DK104363; the National Institute on Deafness and Other Communication Disorders grant R01 DC018562; and National Science Foundation Graduate Research Fellowship DGE-1842487.

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Fasting-mimicking diet reduces signs of dementia in mice

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Fasting-Mimicking Diet Reduces Signs of Dementia in Mice

Short cycles of a low-calorie diet that replicates fasting appeared to reduce inflammation and delay cognitive decline in mouse models of Alzheimer’s disease; initial data indicates diet’s safety in Alzheimer’s patients.
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Cycles of a diet that mimics fasting appear to reduce signs of Alzheimer’s in mice genetically engineered to develop the illness, according to a new USC Leonard Davis School of Gerontology-led study.

The study appeared in Cell Reports on Sept. 27.

The researchers, led by Professor Valter Longo in collaboration with Professors Christian Pike and Pinchas Cohen, found that mice that had undergone several cycles of the fasting-mimicking diet showed less Alzheimer’s pathology. The researchers found lower levels of two major hallmarks of the disease: amyloid beta – the primary driver of plaque buildup in the brain – and hyperphosphorylated tau protein, which forms tangles in the brain. They also found that brain inflammation lessened and better performance on cognitive tests compared to the mice that were fed a standard diet.

The fasting-mimicking diet (FMD) is high in unsaturated fats and low in overall calories, protein, and carbohydrates and is designed to mimic the effects of a water-only fast while still providing necessary nutrients. Previous research led by Longo has indicated that brief, periodic FMD cycles are associated with a range of beneficial effects, including the promotion of stem cell regeneration, lessening of chemotherapy side effects, and lowering risk factors for cancer, diabetes, heart disease and other age-related diseases in mice and humans.

Promising results in mouse models of Alzheimer’s
Alongside healthy mice, the team investigated two mouse models of Alzheimer’s, E4FAD and 3xTg. During the study, mice were fed the fasting-mimicking diet for 4 or 5 days twice per month and were allowed to eat normally between FMD cycles. In a long-term experiment to see the effects in aged mice, 3xTg mice were placed on the diet for 30 cycles in 15 months. Shorter-term experiments in both 3xTg and E4FAD mice ranged from a single FMD cycle to 12 cycles in 6 months.

In both models, mice who underwent FMD cycles showed promising reductions in amyloid beta – which form the sticky, disruptive plaques in the brain – and tau pathology compared to mice eating a standard diet. The FMD mice also showed lower levels of brain inflammation, including a reduction in the number of active microglia, the immune cells that seek and destroy pathogens and damaged cells in the brain. In addition, mice on the diet demonstrated a lower level of oxidative stress, which plays a role in Alzheimer’s pathology by damaging neurons and contributing to the accumulation of amyloid in the brain. The study specifically pointed to the free radical “superoxide” as a central culprit in the damage occurring in these Alzheimer’s mouse models, Longo explained.

Outwardly, mice of both Alzheimer’s models who underwent the FMD showed less cognitive decline than their standard diet counterparts. Cognitive behavior, including exploration and performance within mazes, was tested in young mice before the dietary regimen began and again after several months of either a standard diet or twice-monthly FMD cycles. The Alzheimer’s mice given the FMD significantly outperformed the Alzheimer’s mice given standard diets and in some instances performed similarly to the non-Alzheimer’s-prone control mice, indicating that cognitive decline had been significantly slowed.

The FMD cycles appeared effective in reversing a range of pathology markers but also cognitive defects in two of the major mouse models for Alzheimer’s disease. Longo said that the results are promising.

Small clinical study explores feasibility for humans
In addition to the study in mice, Longo and colleagues also included data from a small Phase 1 clinical trial of the fasting-mimicking diet in human patients diagnosed with mild cognitive impairment or mild Alzheimer’s disease. Forty such patients who were otherwise healthy and had family support were randomized to either a once-monthly, 5-day fasting-mimicking diet or a 5-day period in which lunch or dinner was replaced with a meal based on pasta or rice.

Initial data indicates that the FMD is safe and feasible for patients with mild impairment or early Alzheimer’s disease. Further tests in the ongoing clinical trial will measure cognitive performance, inflammation and more, Longo said.

Other early trials of the diet published by Longo and colleagues have indicated other benefits of a monthly cycle, such as a loss of fat mass without loss of muscle mass and improved cardiometabolic risk factors, especially in overweight or obese people.

Notably, in a recently published clinical trial in which Longo was a co-author, FMD cycles were associated with disease regression in diabetes patients. Diabetes nearly doubles the risk of developing Alzheimer’s disease, per the Alzheimer’s Association.

Other authors included co-first authors Priya Rangan, Fleur Lobo and Edoardo Parrella of USC; Terri-Leigh Stephen, Christian J. Pike, Pinchas Cohen, Kyle Xia, Katelynn Tran, Brandon Ann, and Dolly Chowdhury of USC; Anna Laura Cremonini, Luca Tagliafico, Angelica Persia, Irene Caffa, Fiammetta Monacelli, Patrizio Odetti, Tommaso Bonfiglio, and Alessio Nencioni of the University of Genoa, Italy; Nicolas Rochette, Marco Morselli, and Matteo Pellegrini of UCLA; Mary Jo LaDu of the University of Illinois at Chicago; and Martina Pigliautile, Virginia Boccardi, and Patrizia Mecocci of the University of Perugia, Italy.

The study was funded in part by National Institutes of Health/National Institute on Aging grants AG20642, AG025135, and P01 AG034906 to Longo; AG058068 to Pike; the NIA T32 training grant AG052374 to Rangan; and the PE-2016-02362694 and PE-2016-02363073 grants by the Italian Ministry of Health to Odetti, Mecocci, Monacelli, and Longo. The LaDu lab is funded by NIH (NIA) R01 AG056472, R01 AG057008, UH2/3 NS10012, R56 AG058655, 1R44 AG060826, institutional funds from the College of Medicine at the University of Illinois, Chicago, and generous philanthropic contributions.

Longo is the founder of and has an ownership interest in L-Nutra; the company’s food products are used in studies of the fasting-mimicking diet. Longo’s interest in L-Nutra was disclosed and managed per USC’s conflict-of-interest policies. USC has an ownership interest in L-Nutra and the potential to receive royalty payments from L-Nutra. USC’s financial interest in the company has been disclosed and managed under USC’s institutional conflict-of-interest policies.

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Disadvantaged workers face more challenges in retirement, too

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Study: Disadvantaged workers face more challenges come retirement
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As Healthy Aging Month comes to a close, research from Price School associate professor Emma Aguila documents the varied work pathways of America’s increasingly diverse older workforce.

Highlights:

? Workers with limited job opportunities face more obstacles in retirement – perpetuating inequities among demographic groups
? Various disparities, along with other inequities such as health and education, perpetuate income inequality come retirement
? Employer-sponsored pension plans cover about two-thirds of white workers, but just over one-third of Latino workers

American workers with limited job opportunities during their working years face obstacles in retirement too, perpetuating inequities among demographic groups. That’s according to research conducted by Emma Aguila, a USC Price School associate professor and expert on the economics of aging.

Aguila’s research, which was reported in a recent study for the National Academy of Sciences, Engineering and Medicine, sheds light on some of the challenges many older Americans face in planning for retirement or seeking to work longer into their lives.

As Healthy Aging Month comes to a close, the study documents the varied work pathways of America’s increasingly diverse older workforce. Disadvantaged older workers are more likely to be forced into involuntary retirement due to job loss or disability, for example. They may take on informal gigs that don’t contribute to the Social Security system, such as nannying. Hispanic and Black Americans in mid-skilled jobs have been particularly affected by automation, as well.

Additionally, historically disadvantaged groups are less likely to have control over where, when and how much they work at older ages.

Despite the growing diversity of the aging workforce, much of the existing research on older workers has focused on the experiences of economically and socially advantaged groups, the study concluded.

“I think we’ve been analyzing the population as if they all behave the same, like they all have full-time jobs and they follow this career path and then they retire,” Aguila said. “But I think what we really need to consider is the heterogeneity across the population.”

Take pensions, for example. Employer-sponsored plans covered about two-thirds (64.6%) of non-Hispanic white workers, 55.7% of Black workers, and just over one-third (38.4%) of Hispanic workers, Aguila reported.

Occupational segregation

Those differences can be explained in large part by occupational segregation. Whites are more likely to work at larger firms that provide pensions, while Blacks are more likely employed in the public sector, which often offers pensions, too. Hispanics, by contrast, are more likely to work at smaller firms or part time – jobs that are less likely to include employer-sponsored retirement plans.

Disparities like this, along with other inequities such as health and education, further perpetuate income inequality come retirement. “The more advantaged workers, they not only have Social Security, but they will have other sources of income” like savings or pensions, Aguila noted. “So the inequality continues.”

The National Academy tapped Aguila to analyze existing data and research on vulnerable older workers, as part of a broader report published in May examining the aging American workforce. She reported that there is not enough literature on the experience of these populations, limiting insight into how inequality in retirement and work opportunities affects older adults.

Aguila recommended that future research take a “life course perspective” on inequity in work and retirement. Gathering such data would require following people over time to better understand inequalities in later adulthood. Doing so is necessary because the causes of unequal work and retirement pathways begin long before age 50, she explained.

Pandemic effect
Aguila conducted her research just as the COVID-19 pandemic swept the country, putting older adults at heightened risk of serious illness or death, while prompting employers to lay off workers or send them home to work remotely. In many ways, the pandemic and the ensuing turmoil in the job market underscore the issues Aguila studied.

Still, she said it’s too early to know whether the pandemic exacerbated the problems she highlighted in her study.

“More research will come out,” Aguila said of the pandemic’s impact on older workers. “We will be able to understand better whether these issues were exacerbated.”

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Traditional incentives don’t offset COVID vaccine hesitancy

Neither money nor other nudges are enough to persuade vaccine-hesitant people to get the COVID-19 vaccine, a new USC study shows.

The findings, published recently in the journal Vaccine, suggest the standard public health playbook may be ineffective, and mitigating future pandemics may require stronger policy levers such as employer rules or government mandates.

“There is literature and evidence from other vaccination campaigns like the flu, and even some childhood vaccinations, showing that financial incentives do move the needle. We were expecting similar results,” said Mireille Jacobson, an economist and associate professor at the USC Leonard Davis School of Gerontology, co-director of the Aging and Cognition Program at the USC Schaeffer Center for Health Policy & Economics and the study’s first co-author. “Apparently, people have much stronger beliefs and objections about COVID-19 vaccination.”

COVID vaccine hesitancy: Vaccinations stalled after 2021 rollout

Despite rapid initial uptake, COVID-19 vaccinations in the United States stalled within a few months of widespread rollout in 2021. In response, many state and local governments, employers and health systems used public health messaging, financial incentives and creative scheduling tools to increase vaccine uptake.

In mid-2021, months after vaccines were widely available and COVID deaths continued to mount, researchers evaluated vaccination “intentions” – stated plans to get vaccinated — versus actual vaccine uptake. They recruited 2,701 unvaccinated members of a Medicaid managed care plan in California to fill out a survey and randomly assigned them to one or more of the following conditions – a video message to encourage vaccination; $10 or $50 financial incentives for vaccination; or access to a simple vaccination appointment scheduler.

The average age of survey respondents was 36.4 years; 74% were female, 36% self-identified as white, 31% as Black and 34% as Latino. About two-third of respondents received care through Contra Costa Regional Medical Center. The median self-reported household income was between $20,000 to $29,999 and 8% of respondents had less than a high school degree. As for political leanings, 55% supported Joe Biden in the 2020 presidential election and 15% supported Donald Trump.

Interventions’ impact on COVID vaccine hesitancy

The respondents were spread evenly across the study’s different groups. The primary goal was to see whether participants received at least one dose of the COVID-19 vaccine within 30 days of recruitment.

The result: Public health messaging increased the number of people who said they would seek vaccination — but none of the interventions increased vaccination rates.

What’s more, vaccination rates declined by about 4 percentage points when money was offered among two groups: those 40 and over and those who supported Trump in the 2020 presidential election. These groups had the lowest rate of vaccination intentions in the sample.

“The main lesson I took away from this is that, in our increasingly tribal and politically polarized environment, some people have become so entrenched in their beliefs that a nudge is just not enough to get them to act on simple, widely accepted medical advice,” said co-first author Tom Chang, an associate professor of finance and business economics at the USC Marshall School of Business. “In some cases, the narrative seems to be more important than life and death.”

Other highlights from the study include:

  • More than 30% of vaccine eligible subjects remained unvaccinated despite living in county with highest state vaccination rate.
  • 1% of participants expressed intentions to get vaccination within 30 days.
  • Vaccination intentions increased by 8.6% in response to a health consequences video.
  • A 10% increase in vaccination intentions was associated with only a 1.5% increase in actual vaccinations.

About the study: In addition to Jacobson and Chang, other authors of the study include Manisha Shah of UCLA, and Rajiv Pramanik and Samir B. Shah of Contra Costa Regional Medical Center.

The research was supported by J-PAL North America and the National Institute on Aging (P30AG034532).

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Newly discovered protein connected to Alzheimer’s Disease risk

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https://gero.usc.edu/2022/09/20/alzheimer-risk-mitochondria-protein (will not be live until embargo lift)

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NEWLY DISCOVERED PROTEIN CONNECTED TO ALZHEIMER’S DISEASE RISK

A mutation in the small protein SHMOOSE is associated with Alzheimer’s risk and highlights a possible target for treatment.
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A mutation in a newly discovered small protein is connected to a significant increase in the risk for Alzheimer’s disease, expanding the known gene targets for the disease and presenting a new potential avenue for treatment, according to a new USC Leonard Davis School of Gerontology study.

The protein, called SHMOOSE, is a tiny “microprotein” encoded by a newly discovered gene within the cell’s energy-producing mitochondria. A mutation within this gene partially inactivates the SHMOOSE microprotein and is associated with a 20-50 % higher risk for Alzheimer’s disease across four different cohorts. Nearly a quarter of people of European ancestry have the mutated version of the protein, according to the researchers.

The research appears Wednesday, September 21 in the journal Molecular Psychiatry.

The researchers say that both the substantial risk and high prevalence of this previously unidentified mutation differentiate it from other proteins involved in Alzheimer’s disease. Apart from APOE4 — the most potent known genetic risk factor for the disease — only a limited number of other gene mutations have been identified and these only mildly increased risk by less than 10%. Also, because the microprotein is approximately the size of the insulin peptide, it can be easily administered, which increases its therapeutic potential.

“This discovery opens exciting new directions for developing precision medicine-based therapies for Alzheimer’s disease, focusing on SHMOOSE as a target area,” said Pinchas Cohen, professor of gerontology, medicine and biological sciences and senior author of the study. “Administration of SHMOOSE analogs in individuals who carry the mutation and produce the mutant protein may prove to have benefit in neurodegenerative and other diseases of aging.”

Brendan Miller, ’22 PhD in neuroscience graduate and first author of the study, used big data techniques to identify genetic variations in mitochondrial DNA associated with disease risk. After analyses revealed a gene mutation increased Alzheimer’s disease risk, brain atrophy, and energy metabolism, Miller and his colleagues discovered that the mutated gene coded for the SHMOOSE microprotein and began studying its mutated and default forms. The researchers stated SHMOOSE is the first mitochondrial-DNA-encoded microprotein to have been detected using both antibodies and mass spectrometry.

The microprotein appears to modify energy signaling and metabolism in the central nervous system. It was found in mitochondria of neurons and its levels in cerebrospinal fluid correlated with biomarkers of Alzheimer’s disease. A variety of cell culture and animal experiments showed that SHMOOSE alters energy metabolism in the brain in part by inhabiting a crucial part of the mitochondria, the inner mitochondrial membrane.

An emerging field of study

Miller said the findings highlights the importance of the relatively new field of microproteins. For decades, scientists have studied biology mostly by considering a set of 20,000 large protein-coding genes. However, new technology has highlighted hundreds of thousands of potential genes that encode smaller microproteins.

“The field of microproteins is still so new,” Miller said. “We don’t yet know how many microprotein genes are even functional, and the cost to study a potential microprotein one-by-one from a list of thousands is just too expensive and inefficient. The approach my colleagues and I used to detect SHMOOSE shows the power of integrating big genetics data with molecular and biochemical techniques to discover functional microproteins.”

USC Leonard Davis researchers are leaders in the study of microproteins, especially those coded within the mitochondrial genome. In 2003, Cohen and his colleagues were one of the three research teams to independently discover the protein humanin, which appears to have protective health effects in Alzheimer’s, atherosclerosis and diabetes. In the past few years, the Cohen Laboratory discovered several other mitochondrial microproteins, including, small humanin-like peptides, or SHLPs, and a microprotein called MOTS-c, an exercise-mimetic peptide that has entered clinical trials for obesity and fatty liver.

Additional coauthors include Su-Jeong Kim, Hemal H. Mehta, Kevin Cao, Hiroshi Kumagai, Neehar Thumaty, Naphada Leelaprachakul, Henry Jiao, Thalida E. Arpawong, Eileen Crimmins, Meral A. Tubi, Evan T. Hare, Meredith N. Braskie, Lea Decarie-Spain, Scott E. Kanoski, Lu Zhao, Arthur W. Toga, Junxiang Wan, and Kelvin Yen of USC; as well as Joan Vaughan, Jolene Diedrich, and Alan Saghatelian of the Salk Institute for Biological Studies; Nilufer Ertekin-Taner of the Mayo Clinic; and Francine Grodstein and David A. Bennett of the Rush University Medical Center.

The study was supported by NIH grants P30AG10161, P30AG072975, R01AG15819, R01AG17917, U01AG61356, R01AG069698, RF1AG061834, R01AG068405, P30AG068345, P01AG055369, DK118402, F31 AG059356, and T32 AG00037; as well as The Quebec Research Funds Postdoctoral Fellowship. Intellectual property related to SHMOOSE has been filed by the University of Southern California.

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