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An inevitable by-product of metabolism, advanced glycation end products (AGEs) are toxic molecules formed when proteins, DNA and fats become bound after exposure to sugar.  They are also in some of the foods we eat.

 Pankaj Kapahi thinks the research community has neglected the importance of AGEs because they are challenging to study. Now he is on a mission to get scientists to focus on them as a driver of many age-related diseases. The Buck professor makes his case in a review article recently published in the journal Cell Metabolism; the work also gives us good reason to avoid foods that contain AGEs. (More on food later, but for now, try to hold off on the barbequed ribs.)

AGEs affect nearly every cell type and our bodies have inherent defense mechanisms that can clear them. But the production of AGEs really ramps up when blood sugar is high, and eating a typical high-carbohydrate, highly processed Western diet can overwhelm those natural defenses. Further, some of us are likely to be genetically prone to develop more of them, no matter what we eat.

AGEs and disease

AGEs make our cells old before their time, and over time the molecules accumulate in our tissues. The AGEs cause chronic inflammation, make proteins lose their shape, and send our metabolism into a sugar burning state, making it hard to lose weight. To make matters worse, the molecular damage from AGEs is irreversible.

AGEs contribute to obesity and metabolic syndrome. They’ve long been implicated in insulin-resistant type 2 diabetes (which affects more than 29 million people in the U.S.) and are linked to its complications – diabetic nerve pain, retinopathy, cardiomyopathy, and kidney disease. In addition, AGEs are now seen as potential players in neurodegeneration.  Recent findings associate AGEs with familial, early-onset and sporadic forms of Parkinson’s disease, and with proteins linked to Alzheimer’s disease.  In one study, plaques extracted (post-mortem) from brains of patients with Alzheimer’s show a 3-fold increase in AGEs content compared to age-matched individuals who died from other causes.  AGEs are even found in cataracts.

Knowing what we know now, it seems almost quaint that science once viewed AGEs as a phenomena similar to wrinkles – they just happened and were considered mysterious and mostly inconsequential.

The challenges and opportunities for researchers

The chemistry behind the formation of AGES was discovered in 1912and an AGEs-based theory of aging was proposed more than three decades ago. Kapahi says interest in the then red-hot field flagged when a drug designed to clear AGEs in diabetic kidney disease failed in clinical trials in 1998. “Previous research focused on addressing AGEs outside of the cell, in the blood and in serum. The problem is much bigger when AGEs go into the cells, that’s where we need to focus the attention.”

But it’s nearly impossible to study the biological development of AGEs and their implications in humans because they take decades to accumulate and there are obvious ethical concerns in encouraging the development of the toxic molecules in test subjects.  So how to get researchers excited about understanding and exploiting the biology of AGEs? Kapahi says the way to get at the pathways involved in AGEs lies in simple animals including yeast, nematode worms, and flies.  “We can model the diseases in these animals. Rather than waiting 30 years to see what happens in a human, we can see AGEs in nematode worms in two weeks,” he said.

Alejandro Gugliucci, a professor of Biochemistry and Associate Dean of Research at Touro University California co-authored the review.  He is an expert on the bad effects of sugar, particularly fructose which is used to sweeten many processed foods and beverages. Even though he works on efforts to study and stem sugar consumption in humans, he echoes Kapahi’s enthusiasm for basic research in simple animals.  “It’s the best way to get at the genetics and the biology behind AGEs. It’s the best way to screen compounds that could quash them,” he said. “If it doesn’t work in simple animals, it’s not going to work in humans. That’s where we need to start.”

Promising results from the Kapahi lab

Scientists in the Kapahi lab have found a sensor related to AGEs and the complications of diabetes in the nematode C. elegans. Publishing in Current Biology they identified two natural compounds which prevented nerve damage in worms experiencing a similar hypersensitivity to touch as do humans who suffer from diabetic neuropathy. AGEs have also been implicated in neuropathy in mice and humans.  “The worm findings gave us a pathway to study many of the ravages of type 2 diabetes, I’m sure there are others,” said Kapahi.

The lab is also working on a project exploring a link between diabetes and Parkinson’s disease. Researchers identified a gene that produces an enzyme that detoxifies the highly reactive compounds that cause AGEs. Mutations in the gene are linked to a familial form of Parkinson’s.  “The hope is to develop a new treatment for Parkinson’s,” said Kapahi. “The research also holds the tantalizing possibility that compounds that target this gene could be valuable in treating a number of age-related diseases.”

Okay, but what about AGEs in food? What do we eat?

If you want to see the effect of sugar binding with proteins and fats, look into your frying pan. The brown crust on grilled or pan-seared red meat is pure AGEs.  Kapahi urges people to avoid cooking with dry heat, opting instead for steaming, stewing, poaching and braising.  Frying with oil isn’t great either. According to the American Diabetes Association (ADA), fried chicken has more than six times the amount of AGEs when compared to a same-size serving of boiled chicken.

Boiled grains and sandwich breads are low in AGE’s but ADA experts say AGEs content can soar when those grains are processed into crispy brown crackers or sugar-sweetened cookies. Milk and yogurt are low in AGEs, but when moisture is removed and fat is concentrated (butter and cheese) the AGEs content rises dramatically.  For those with an insatiable hankering for grilled foods, the ADA recommends throwing fruits and vegetables on the grill. You’ll still get some AGEs, but in a small amount compared with grilled meats.

“Unfortunately AGEs taste great, even the worms and flies prefer them when they have an option,” says Kapahi, who often gets good-naturedly labeled as a killjoy at neighborhood parties. “Overall I think it’s good to follow a Mediterranean-type diet with lots of vegetables and whole grains with small portions of meat or other proteins.”

Thanks to the Buck Impact Circle

The Buck Impact Circle, a donor group that pools its resources to support collaborative early-stage research at the Institute, has chosen to fund many projects involving the Kapahi lab. In addition to supporting research on the complications of diabetes and the link between AGEs and Parkinson’s disease, the group has also funded projects aimed at determining if a ketogenic diet can protect against the complications of diabetes. This year they put their money toward research that tests compounds that show promise in lowering AGES associated with Alzheimer’s disease pathology.

“I am extremely grateful to the Impact Circle for their support and encouragement,” says Kapahi. “Being able to interact directly with these donors is so personally rewarding, it helps remind everyone in the lab that our work is really focused on human health.”

“It has been such a joy and privilege to follow Pankaj’s research and to support his progress,” said Buck Institute trustee Bob Griswold.  He and his wife Alex are founding members of the Impact Circle.  “Belonging to this group is exciting and educational. Nothing compares to having a personal investment in work aimed at helping us all live better longer.”

Next steps in the research

AGEs are a group of compounds that include more than 20 different targets. Kapahi says there is a lot of work for researchers to tackle and he’s happy to talk to anyone interested in the field.

Touro’s Gugliucci is particularly excited about collaborating with Kapahi to work on compounds that enhance our natural defenses against the formation of AGEs. “This is the way to go, to prevent the formation of AGEs in the first place” he said. “I think there’s a good chance that we’ll be able to get NIH funding to move the work forward into mammals and ultimately humans.”

Kapahi says there are many questions that need answers. Why do some people get AGEs-associated diabetic complications even before they develop full-blown diabetes? Does aging affect the body’s efforts to detoxify AGEs and can we address the problem from that angle?  What are the different mechanisms to detoxify AGEs? How do our genetics influence AGEs accumulation and detoxification? Can we make compounds that slow the progression of AGEs accumulation? What diseases can they help treat?

Finally, Kapahi wants you to remember that he’s happy to talk about the research and be on the stump for AGEs. Just be sure there’s a friendly, open-minded crowd when you invite him to dinner.

Midstate Construction Corporation recently completed rehabilitation of Walnut Place (West Marin Senior Housing), a senior residential community in Pt. Reyes, CA for owner EAH Housing, a nonprofit affordable housing development and management organization.

Designed by TWM Architects, this project included rehabilitation of a 25 unit existing senior residential facility completed in 1986.

The scope of work included interior and exterior renovations; seismic upgrades, new windows, roofing, siding, flooring, appliances, cabinets, sinks, covered porch, new common area, and an extensive community garden renovation.

Novato and Sonoma-based SolarCraft has completed a 143.3 Solar Electric System at Sonoma Academy’s newly constructed Janet Durgin Guild & Commons building.  The building is the first of its kind in the North Bay, an environmental and human health model based primarily upon the Living Building Challenge criteria: to create structures that not only minimize a building’s impact on the environment but help repair it.

Designed and engineered to offset 105% of total energy usage the solar photovoltaic system is roof mounted, consisting of two solar arrays, one of which is integrated with the ‘living roof’, installed by Symbios Ecotecture, using filtered greywater.  This 19,500 sq. ft. building is designed to create more energy than it uses, thereby returning surplus energy to the grid, making it a zero net energy (ZNE) and zero net water building.  “We are honored to be working closely with Sonoma Academy, WRNS Studios architects and XL Construction to help make this visionary project a reality”, says Robert Gould, Director of Commercial Sales at SolarCraft.  “It proves what is possible with innovative thinking to create a better world for all and the next generations. It’s an example that students, and the whole community, can learn from and be inspired by”.

In addition to the new photovoltaic system, a 208 kW solar power project was designed and installed by SolarCraft in 2016, offsetting energy use in their existing campus buildings.

“We are thrilled with the thoughtful design in every aspect of this project which enabled us to use free natural resources like natural light and fresh air”, stated Janet Durgin, Head of School and project namesake. “These elements make a huge difference in our teachers’ ability to teach and our students’ ability to learn. We intend to use the building and its energy systems themselves to teach sustainability in community. That is exactly the greater purpose we hope Sonoma Academy brings to the greater North Bay.”

The new solar power system will generate 210,000 kWh annually, enough electricity to power about 17 average homes per year.  It will avoid production of 156 metric tons of carbon dioxide emissions per year, which is the equivalent of removing nearly 10 million miles of driving over the next 25 years.  That’s also comparable to the air pollution removed by 184 acres of trees annually.

In addition to the rigorous certification requirements of the Living Future Institute’s Living Building Challenge, Sonoma Academy is Seeking LEED Platinum, ZNE, WELL Education Pilot, and LBC Petal certification for this progressive structure.

About Sonoma Academy
Sonoma Academy is the only independent, college preparatory high school in Sonoma County.  On its beautiful 34-acre campus nestled at the base of picturesque Taylor Mountain in South Santa Rosa, Sonoma Academy students are able to explore their interests and passions in a challenging environment that prepares them for college and life beyond.  The Academy has undertaken a program of environmental excellence, aiming for a zero net-energy standard for its new facilities.

SolarCraft is100% Employee-Owned and one of the largest green-tech employers based in the North Bay for over 35 years.  SolarCraft delivers Clean Energy Solutions for homes and businesses including Solar Electric, Solar Pool Heating and Battery / Energy Storage.  With over 7,000 customers, our team of dedicated employee-partners is proud to have installed more solar energy systems than any other company in the North Bay.www.solarcraft.com.

Charitable events combined to raise more than $95,000 for Northern California non-profit groups during the 31^st Toyota NHRA Sonoma Nationals at Sonoma Raceway, July 27-29.

The proceeds from the majority of events will benefit Sonoma County youth organizations through the Sonoma Chapter of Speedway Children’s Charities (SCC), the charitable arm of the raceway, which has distributed more than $6 million to qualified youth groups since 2001.

Fundraising kicked off on Thursday, July 26, at the 12^th annual Eric Medlen Nitro Night at Viansa Sonoma, which generated more than $35,400 for Sonoma County children. The evening honors the memory of Medlen, a native of Oakdale in the San Joaquin Valley, who succumbed to injuries sustained from a testing accident in 2007, and all proceeds from the evening benefit SCC in Medlen’s name.  Since its inception, this event has raised more than $303,400.

This year’s event focused on honoring someone within the drag racing community who embodies Medlen’s best qualities and has shown support of charitable efforts. The first SCC Eric Medlen Spirit Award was given to 2016 NHRA Funny Car Champion Ron Capps.

Special guests of the evening included Capps, emcee Jack Beckman, Scotty Pollacheck, Brandon Bernstein and J.R. Todd who helped auction off ticket and experience packages generously provided by Ron Capps, which all together netted $12,550. More than 100 attendees turned out for the dinner, including Medlen’s mother, Mimi, and his father, John.

Additionally, $1,460 was raised from donations at the Eric Medlen Ice Cream Social on Sunday, July 29. Following the final round of eliminations, fans were invited to enjoy a free scoop of ice cream, compliments of Clover Sonoma, and make a donation to SCC.  Speedway Children’s Charities also netted donations through the “Let’s Go Karting” charity raffle and the “Cash for Kids” display.

In addition to the proceeds generated for SCC, Levy Restaurants, the official caterer of Sonoma Raceway, hosted eight local non-profit groups to support concession stands around the facility. In return for their hard work, Levy gives back a portion of sales to support those non-profit organizations. These groups, including California Martial Arts Institute, Casa Grande Cheer, Petaluma Elks Lodge, Native Sons of the Golden West, O’hana Wa’a Outrigger Canoe Club, Rohnert Park-Cotati Cheer, Santa Rosa Cheer and Vallejo Raiders Youth Football, received a total of $57,392 from NHRA weekend concession sales.

For more information about the Sonoma Chapter of Speedway Children’s Charities and future charitable events or to make a donation, visit SonomaRaceway.com/scc or contact Cheri Plattner at (707) 933-3950 or cplattner@SonomaRaceway.com. If your non-profit group is interested in working with Levy Restaurants to fundraise at an upcoming event, contact Kimberly Conte at kconte@Levyrestaurants.com or 707-939-1454.

Arrow Benefits of Petaluma and The Personnel Perspective of Santa Rosa plan to open a joint office in Napa.

They have been “sister companies” since 2014, according to the announcement. The pairing of the companies in a new location will offer “administration, benefits, human resources, management training and development, and recruiting under one umbrella.”

Karen Alary, managing partner at The Personnel Perspective, described the action as a “a logical move for both firms.”

Arrow Benefits Group Managing Partner Stephen McNeil said the combination is an “evolution of our partnership” to offer human resources and benefits under one roof. Arrow now has nine locations in the San Francisco Bay Area and Southern California.

Linda Hansen will open and manage the Napa office. She has more than 25 years of human resources and benefits experience and has spent the past 10 years working in the Northern California wine industry. Her wine business experience includes strategic support within all areas within a winery and vineyard operation, including winemaking, supply chain, operations (bottling, distribution and maintenance), administration (finance, IT and human resources), marketing and direct-to-consumer efforts.

The firms plan a ribbon-cutting and evening celebration at the new location, 1303 Jefferson Street, Suite 100A, in Napa on July 24 for 5:30–7 p.m. RSVP for entry to maryh@arrowbenefitsgroup.com