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It’s becoming more and more obvious that the environment we live in has a lot to do with life expectancy and overall health.  Is the air clean? Are there toxins in our homes and in our neighborhoods? Is there access to healthy foods and safe places to exercise? This growing awareness spawned a workshop hosted by the National Academies of Sciences, Engineering, and Medicine focusing on the integration of the science of aging and environmental health research.  Buck professor Julie Andersen spoke at that conference and co-authored a report published earlier this year highlighting opportunities for synergy and accelerated research between the two fields.

The Buck’s Senior Director of Communications Kris Rebillot talked to Andersen about the overall effort.

Julie, how did you get involved in the conference?

My lab has been looking at the role of neurotoxins in the development of Parkinson’s disease for nearly 20 years.  We established a link between excess iron and Parkinson’s in 2003 and identified the mechanism at play in 2016 and we’ve done a lot of work with the herbicide paraquat which is an established risk factor for Parkinson’s. In 2018 we showed that exposure to paraquat causes senescence in astrocytes, cells that have many supportive roles in the brain. The fact that I study Parkinson’s in the context of aging made me a natural for the conference.

What’s kept the fields of aging research and environmental health apart?

Both fields are relatively “young” when compared to other scientific disciplines. Environmental health has understandably been focused on the impact of environmental exposures on children. Two common examples are the link between lead poisoning and mental development and the impact of air pollution on childhood asthma. There hasn’t been as much of a focus on adults, but that’s changing.

Early on, research on aging was largely centered on understanding the molecular biology of aging without much context, meaning we didn’t look at the external factors that drive age-related changes within cells and tissues. Some studies now estimate that human life expectancy is largely (up to 95%) driven by non-genetic factors which include nearly everything in our environment.  It’s pretty obvious that the two fields need to intersect if we’re going to have a significant impact on overall human health.

 What has stayed with you following the conference and your work with co-authors of the white paper?

I gained a huge appreciation of how social justice factors into the aging process.  People who are financially disadvantaged often live in areas where the air is polluted, experience more mental and emotional stress, and have less access to nature and healthy foods. It seems kind of obvious, but I had never thought deeply about people who find themselves stuck in unhealthy environments and how chronic exposure to environmental stressors leads to increased vulnerability to the chronic diseases of aging. I’m much more sensitive now to the influence of these factors on overall health in aging individuals and the realization that these are as important as physical factors in the aging process.

The paper refers to the “exposome” . That seems like a fairly new term.  What does  it mean?

So, the exposome concept was originally proposed in 2005 to include all cumulative exposures from conception onward. It included diet, lifestyle and the physical environment and it now includes socioeconomic factors and behaviors, including things such as the impact of isolation on health.  There’s a new term and focus that’s coming out of the work called “gerotoxicity”, which looks at how exposure to toxins at any age impacts the aging process.   It could become a new subspecialty in the research world.

Is there a strategy for building a bridge between environmental health and aging research?

It’s no surprise that bridging disciplines takes a lot of multidisciplinary collaborations. In this case we identified toxicology, comparative biology and epidemiology as beginning points.

We need to identify existing or new biomarkers that can be used to help us gain an understanding of how lifetime exposures to toxicants and other physical and social stressors alter biological aging. This would help us understand why older adults often have a diminished ability to compensate and recover from exposure to adverse stressors. We really need to reexamine all of the factors known to drive aging – cellular senescence, protein instability, mitochondrial dysfunction, and DNA instability, among others, through the novel lens of gerotoxicity.

We talked a lot about the role of the microbiome at the conference. Current data suggests that environmental factors can contribute to alterations in the gut microbiome. There’s a growing interest in the microbiome in our field because age-related changes in the gut have been associated with systemic inflammation, immune and metabolic dysfunction, and even neurodegenerative diseases.  We need to understand the role the environment plays in driving those changes.

In my lab we study autophagy, a process whereby the cells recycle damaged proteins and mitochondria. Autophagy declines with age and has been identified as a player in many age-related diseases.  There’s every reason to surmise that environmental stressors are likely contributing to that decline.

So what happens next?

Great question. In the larger context a lot will depend on whether the NIH, probably through the National Institute on Aging and the National Institute of Environmental Health (NIEH), decide to fund projects that support the two fields working together.  Often conferences like the one I attended are put together with the express intent of giving scientists opportunities to get to know each other and to brainstorm about possible synergies.  I hope the NIH took note and makes this research a priority.

After the conference, I personally collaborated with one of the co-authors who works at the NIEH to look at the brains of aging mice. Some were raised in a germ-free environment (meaning they had no microbiome) and others in a normal environment. We got some interesting data that suggest that microglia, which can get inflamed with age, appear to do better in mice raised in a normal environment.

I expect that the conference will result in additional collaborations, similar to the one I just described. It would be great if the federal government invested in the larger scope. It’s an endeavor I’d be excited to be part of.

https://www.buckinstitute.org/blog/a-call-for-researchers-in-aging-and-environmental-health-sciences-to-join-forces/

BPM LLP, one of the 40 largest public accounting and advisory firms in the country, intends to expand its footprint in Northern California, adding a Sacramento office through a combination with Avaunt Ltd. CPAs and Consultants expected to be complete August 1. This news follows BPM’s recent announcement of its upcoming combination with Santa Rosa, Calif.-based Elliott CPA Group Inc. expected for July 1.

“As a firm, BPM is committed to meeting clients where they are, which is why we are so pleased Avaunt plans to join us, providing an office and top-notch resources in California’s capital city,” said BPM North Bay Partner-in-Charge Michelle Muth Ausburn. “Throughout their long history in the market, Perry, Dorothea and their team have demonstrated a people-first approach much like BPM’s. Our deep relationships and business connections are instrumental to helping our clients get established, grow and mature.”

Founded by Perry Ghilarducci in 1985, Avaunt Ltd. focuses on serving businesses in the restaurant and hospitality space, as well as medical industry practices and professionals. With a growth-oriented approach, the firm helps guide clients throughout their business lifecycles with tailored services and solutions that take them from startup through exit.

“The Sacramento region has seen unprecedented growth in the last five years, and we could not be happier to combine forces with the 900+ members of the BPM team to meet the market demands,” noted Ghilarducci. “BPM brings new depth to the services we currently offer our clients, as well as an expanded menu of solutions that will help further our clients’ business goals in the region and well beyond.”

Avaunt Ltd. will rebrand under the BPM name. The Sacramento office benefits from synergies with BPM’s other Northern California regional offices, located in Fairfield, Menlo Park, San Francisco, San Jose, Santa Rosa, St. Helena, Stockton and Walnut Creek. BPM also has a strong presence in Southern California, as well as offices in Oregon, Washington and India. The Firm’s specialized professionals span across the globe.

About BPM 

BPM LLP is one of the 40 largest public accounting and advisory firms in the United States. With a global team of more than 900 colleagues, we help clients succeed around the world. We offer a cross-functional approach that gives clients direct access to the best and most qualified resources.  To learn more, visit our website.

https://www.bpm.com/news/bpm-expands-into-sacramento-through-upcoming-combination-with-avaunt-ltd/?utm_content=213268358&utm_medium=social&utm_source=linkedin&hss_channel=lcp-16742

Selected by the Board of Trustees of the California State University Ron Rubin, an industry beverage authority received an honorary degree of Doctorate of Humane Letters at Sonoma State University (SSU) School of Business and Economics (SBE) commencement ceremony May 21st. CSU and SSU held Ron Rubin’s career up as a model for the class of 2022, noting more than four decades of visionary contributions as a businessman who has built and led three beverage and wine companies worldwide, given back to the community as a philanthropist, and has been dedicated to the world-class success of the Wine Business Institute (WBI).

“Ron Rubin’s leadership and dedication to the community embody the values of the California State University system which strives to instill in our students: to live inquiring, ethical and productive lives as global citizens,” said Dean Coget, recognizing Ron Rubin’s commitment to serving social good through innovative services and education programs.

“His storied career advancing the business of beverage and his generous philanthropy, make him a true exemplar of the California State University spirit,” noted Ray Johnson, Executive Director of the WBI. “On a personal note, Ron has been a mentor to me throughout my tenure at the Wine Business Institute.  I benefit from his wisdom and guidance regularly.”

Philanthropy plays a major role in Ron Rubin’s general make-up. He is the current President of the Board of Directors for Sonoma State University’s Wine Business Institute, advising on the University’s curriculum. He was a major donor of the Wine Spectator Learning Center’s state-of-the-art education complex, and home of the WBI and over 1600 wine industry graduates. In recent years, he has also been honored by North Bay Business Journal, with their Innovator of the Year Award.

He began the Ron Rubin Winery TRAINED FOR “SAVING LIVES” program. In collaboration with the American Red Cross and ZOLL Medical Corporation, Ron Rubin Winery is covering the cost of one ZOLL AED PLUS (Automated External Defibrillator) unit, to 450 qualifying, California wineries. This sustainability and safety plan is designed to keep visitors to California’s wine country safe, in the event a defibrillator is needed at any of the program’s participating wineries. Each day, California becomes more heart safe, in the possible event that CPR or an AED would be necessary. There are currently 283 wineries participating in the program’ and are now TRAINED FOR “SAVING LIVES,” with over 1600 newly trained staff members ready to take action, if and when necessary.

Mr. Rubin was nominated for this degree by Sonoma State in recognition of his leadership to Sonoma County and his advocacy, advice and support for the university.

About the Wine Business Institute 

The Wine Business Institute (WBI) serves as an intellectual and industry center for faculty, students, and the business community. Founded in 1996 as a partnership between the wine industry leaders and the School of Business and Economics at Sonoma State University, the WBI provides cutting-edge research that informs industry best practices and program curriculum. For more information about degree and certificate programs or wine business research https://sbe.sonoma.edu/winebiz.

About Sonoma State University School of Business and Economics

The SBE is a leading institution of business education in the San Francisco Bay Area, with an emphasis on preparing students to succeed in an economy that is global in nature. Our commitment to sustainable business, diversity, social justice, and global partnerships echoes our core philosophy of purpose-driven leadership. As one of the 50 top-ranked public universities, we have been recognized worldwide for our investments in diversity, social responsibility, and visionary academics. Many classes average fewer than 40 students, allowing close interaction between students and faculty.

This year the Buck’s Impact Circle chose to support the first-ever clinical study to be done at the Buck Institute. The award of more than $120,000 will enable researchers to test blood biomarkers in a small group of older adults who will take a nutritional supplement designed to put the body into ketosis. Strong evidence in mice indicates that ketone bodies, which are produced when the body is starved of carbohydrates, have a positive effect on multiple hallmarks of aging, including oxidative stress, inflammation and mitochondrial function.

“Ketone esters have been mainly studied in the context of healthy young adults,” said Buck assistant professor John Newman, MD, PhD, who will co-direct the trial, which has been dubbed BIKE: Buck Institute Ketone Ester study, together with the Buck’s Lead Translational Scientist Brianna Stubbs, PhD. “We are so grateful for the Impact Circle’s support of this first attempt to directly link nutritional ketosis to aging biomarkers. We think this project will provide breakthroughs, both in the field of aging research, and in the Buck’s overall efforts to engage in clinical trials,” said Newman

Now in its 10^th year, the Impact Circle is a group of like-minded philanthropists who advance scientific discovery at the Buck by pooling their resources to provide seed money for early stage projects. In addition to the satisfaction of supporting ground-breaking research (and tracking its success), they also get a front row seat on the scientific process.

Long-time Impact Circle members Allan and Sydne Bortel are particularly happy with this year’s choice, given that both of them have Alzheimer’s disease in their families.  “We like to lean toward anything that could have an impact on brain health,” said Allan, a retired financial securities analyst. “The project seemed experiment-ready and simple enough to move into humans.  We’re very excited to support the Buck’s first clinical trial and look forward to getting updates about what is discovered.”

Adding blood biomarkers to the mix

The BIKE trial, which is expected to begin in the fall, is being largely funded by a major donor who wishes to remain anonymous. Thirty older adults (65+) will be recruited for a double-blind, placebo-controlled trial which will last for 12 weeks. The study will collect measures of safety, tolerability, physical and cognitive function and quality of life. The Impact Circle award will allow researchers to go further, by enabling an examination of blood samples from study participants for biomarkers of biological aging mechanisms thought to be affected by ketone bodies. Researchers will measure markers of inflammation, oxidative stress, and mitochondrial function, as well as epigenetic clocks.

“In the laboratory Ketone bodies interact with these mechanisms of aging in mice. Now for the first time we’ll start to see if they have the same impact in humans. We need blood aging biomarkers in order to show how the ketone ester is working and move into next-phase studies funded by the National Institutes of Health,” said Newman. “Our ultimate goal is to do a study involving several hundred people in three centers around the country that will change the way we view and use ketone bodies in aging. I can’t emphasize enough how important the Impact Circle’s support is in this regard.”

Stubbs has first-hand experience with clinical trials involving ketone bodies.  She was a study subject herself as a grad student in the United Kingdom when she was an elite rower who won the World Championships twice with Great Britain. She went on to get her PhD in metabolic biochemistry.  “What’s exciting about this upcoming trial is that we want to involve ordinary people in it,” said Stubbs. “Our best case scenario is that we are able to validate the fact that older people can reap the benefits of ketosis without having to change their diets.”

Newman, who is also a practicing geriatrician at the San Francisco VA Medical Center, has a particular interest in how ketone bodies work in older adults.  He wants to see if they could help hospitalized older adults avoid delirium, a sudden change in mental status that is often characterized by confusion, disorientation and sometimes hallucinations.  Newman was the lead author of a study in Cell Metabolism in 2017 which showed that a ketogenic diet improved both healthspan and memory in aging mice. “While I enjoy being a mouse doctor in the lab, I am really eager to see what ketone bodies and other geroscience interventions can do in humans,” he said.

Those interested in receiving updates about the BIKE study should email: BIKE-Study@buckinstitute.org. The study will involve North Bay residents 65 or older.  Recruitment is expected to begin this fall.

More from members of the Impact Circle

In addition to helping fund the BIKE trial, Impact Circle members Alex and Robert Griswold are donating $30,000 to support one of the other Impact Circle projects which is spearheaded by associate professor Birgit Schilling, PhD. Schilling will create a new 3-dimensional human tissue model of cartilage (“knee in a dish”) to screen drugs and develop optimized treatments for osteoarthritis. Schilling’s team, which will include Buck professor Judith Campisi, will focus on the role senescent cells play in the development of age-related osteoarthritis. The team will also study the therapeutic benefits of clearing the cells, which are linked to chronic inflammation in many age-related diseases. The hope is that the new laboratory model, which will closely mimic what really happens in human diseased or aged joints, will increase the success of future clinical trials in human patients.

Lisa Palma, Director of Philanthropy, is particularly grateful for a somewhat return-to-normal for the Impact Circle.  This year’s event was a hybrid; members gathered both in-person and on Zoom.  “The enthusiasm for our research never faltered during the depths of the pandemic, which is a testament to the work being done in our labs,” she said.  “It’s always a thrill to connect our scientists with this group of engaged donors. Everyone benefits from the interaction.”

Sydne Bortel, a retired clinical social worker, says getting to know Buck scientists is part of what keeps her and her husband engaged with the group. “From the beginning we were fascinated to think we could have an actual influence on what was going to be studied at the Buck.  Meeting and enjoying the scientists and getting a greater understanding of their research is a huge plus. It helps keep us smart.”

Membership in the Impact Circle remains open. Because the clinical trial is scheduled to begin in the fall, joining the Impact Circle now means new members still get to enjoy a full-year of member benefits, which include regular progress reports as well as invitations to online and in-person lab updates from the scientists. ​Those interested in getting involved should contact Lisa at lpalma@buckinstitute.org.

https://www.buckinstitute.org/news/the-bucks-impact-circle-supports-a-first-ever-pilot-study-to-look-at-the-effects-of-a-ketogenic-supplement-in-older-adults/

Novato-based Ultragenyx on Thursday afternoon held a ribbon-cutting ceremony to mark the opening of its state-of-the-art research facility, located at 32 Leveroni Court, in the Bel Marin Keys Industrial Park.

The ceremonial event and lab tour that followed was more than two years in the making — not because of construction delays, but because of the pandemic, noted John Pinion, chief quality operations officer and executive vice president, translational sciences.

The 20,000-square-foot lab facility, which was formerly a warehouse, was completed in December 2019, and has been operating continuously since then, he said.

In his remarks on Thursday, Ultragenyx founder and CEO Emil Kakkis recalled that when he started the company in 2010, he didn’t have enough money for Ultragenyx to have its own research building, so he leased space from the nearby Buck Institute on Research and Aging, paying between $30,000 and $40,000 a year.

“From there, we continued to build out further and further, but it became evident at some point in time that we needed to develop our own building and our own space,” Kakkis said. “Fortunately, with the success of the work everyone’s been doing at the company, we were able to build the financial strength required to actually take on a building and invest in it.” The purchase price is not publicly available, said Jeff Blake, senior director of corporate communications.

Kakkis also said Ultragenyx having its own research facility marks another step forward in the company’s work to develop novel treatments for rare genetic diseases.

“We are very pleased to see how much research has gone on, even during the pandemic, and how much this building has contributed already to the development of our pipeline,” Kakkis said.

Ultragenyx also continues to utilize research space at The Buck.

To date, Ultragenyx has three first-ever treatments for rare diseases that have been approved for pediatric and adult patients. They are called Crysvita, Dojolvi and Mepsevii.

The biopharmaceutical company, which currently has 32 employees working in the new research facility, has more than 1,100 employees around the globe. About half of them work in Novato.

The company’s additional U.S. locations outside of California are in Utah and Massachusetts; with global offices in Colombia, Argentina, Switzerland, England, Germany, Japan, Belgium, the Netherlands and Luxembourg, according to Ultragenyx’s website.

https://www.northbaybusinessjournal.com/article/industrynews/ultragenyx-celebrates-new-research-facility-2-years-later-than-planned/