“Will you still need me, will you still feed me, when I’m sixty-four? You’ll be older too.”
That Beatles song turns 50 this year and its writer, Paul McCartney, turns 75 in June. George Harrison, former Beatle, died in 2001 at age 58 of lung cancer and a brain tumor. Italian Emma Morano, the oldest known living person, had her 117th birthday in November.
Cancer is one of many maladies that plague us as we age: Alzheimer’s, Parkinson’s, atherosclerosis, diabetes, arthritis, osteoporosis and hypertension. Eric Verdin, newly appointed CEO at Novato-based Buck Institute for Research on Aging, aims to curb some of these diseases.
“The aging field has been heavy on promise” but delivered scant results, said Verdin, who worked as associate director at San Francisco-based Gladstone Institute for Virology and Immunology. There he studied the role of diet in aging, along with Alzheimer’s.
Verdin, a physician and professor at University of California, San Francisco, replaces former CEO Brian Kennedy, who served about six years and resigned in October. A month later, the board announced Verdin’s appointment along with pledges from a few board members totaling $11 million to shore up Buck’s strained budget, which totals about $35 million a year.
Raising money is essential, Verdin said. He pointed to the recent home run by Unity Biotechnology, a Buck spinoff co-founded by Nathaniel “Ned” David. Unity raised $116 million from six investors in a funding round reported in October. David served as Unity CEO until he became president in October, and Keith Leonard took the CEO role. Leonard and David had co-founded Kythera Biopharmaceuticals, acquired in 2015 by Allergan for $2.1 billion.
Leonard will steer Unity’s push for clinical trials on two drugs, Verdin said. Unity’s science takes aim at arthritis and glaucoma by killing off senescent cells that foster inflammation and disease. The company, founded in 2011 and with offices in San Francisco and at The Buck, has raised a total of $128 million.
Unity has powerhouse funding backers, including ARCH Venture Partners; Fidelity Investments; Mayo Clinic Ventures; Bezos Expeditions, led by Jeff Bezos, Amazon founder; and Venrock and Founders Fund, headed by Peter Thiel, a 49-year-old San Francisco billionaire, Stanford Law graduate and PayPal co-founder.
“Leading this place, I want to push us into medically relevant aging research,” Verdin said. That would go beyond research on C. elegans roundworms and mice studied by numerous faculty members at The Buck. Verdin suggests aligning the institute with organizations that could conduct human clinical trials or use human samples.
Verdin serves as a consultant to Calico, the Google-backed aging-research company founded by Google and headed by CEO Art Levinson.
“I haven’t interacted with them since I’ve been here,” Verdin said after three weeks on the job. “We have a bunch of tenants here. I would love to get them more involved in the scientific community, not just renting space but intricately woven into our fabric.”
Calico has been notoriously secretive since its 2013 founding.
“They can be secretive about key issues,” Verdin said, “but they can still collaborate. We are a lot more than a building. There are incredible people here.”
He intends to promote more sponsorship agreements between the Buck and corporations such as Calico. Funding is difficult to find because anti-aging science is “radically new,” Verdin said.
“We are at an inflection point,” he said. “That’s my prediction. Let’s say Unity generates one drug that fights arthritis. That would be a validation of this whole model. It will happen in the next five years.”
Glucophage, or metformin, is a diabetes medicine used to control blood sugar and shows promise.
“The biggest surprise was that a diabetic on metformin lived longer than non-diabetics,” Verdin said. “Maybe metformin has an anti-aging effect. People tested this in mice. It increases lifespan.”
The FDA supports a large-scale study of metformin’s effects on nondiabetics, but such research needs $50 million, he said.
“In my vision of this place, people will realize they were right all along,” Verdin said. “We have not delivered yet.” Then “people will rally and realize there is incredible value to this.”
GLADSTONE MERGER DEAD
Some in the North Bay have expressed concerns Verdin might be some sort of — as he characterized it — Trojan horse, preparing for a merger with Gladstone
“I’m not here as a member of Gladstone,” he said. ”Those merger talks are dead. I was excited when the talks collapsed. I’m running the show. It allows us to keep our integrity, our autonomy and name.” He was the only faculty member at Gladstone who researched aging.
Verdin, 60, originally from Belgium, experimented with calorie restriction at Gladstone.
“It makes most animal species live longer,” he said, and protects against neurodegeneration and diabetes. Like many people in the aging-research field, he experiments on his own body with occasional fasting as a form of calorie restriction. “I have done different variations,” including lowered carbohydrates as well as “5:2 diets,” where calories are curbed two days a week and regular meals are eaten for five.
TWO EGGS AND COOKIES
Morano, the elderly Italian born in 1899, eats little. “I eat two eggs a day and that’s it,” she said in an interview in The Guardian, “and cookies.”
More than dieting, Verdin exercises. “I love exercising,” he said. “It protects against everything. With cognition, the data coming out is amazing.” He prefers biking and rock climbing. “We go to Joshua Tree once a year with the family. Oh my God, it’s amazing, unbelievable adherence.” Granite at Joshua Tree has a rougher surface than that in Yosemite, he said, and steep rock can be climbed using friction technique.
Gladstone, with a budget of $80 million, studies cardiovascular disease, virology, immunology and neurological disorders. Gladstone’s work on HIV led to discoveries of sirtuin proteins that function as anti-aging genes in yeast. Researchers cloned seven sirtuins in humans. “Three of them were in mitochondria, completely unexpected,” said Verdin, who researched it for 15 years. “They must be targeting other proteins. They make metabolism much more efficient.”
Mitochondria create energy for cells. SIRT1 helps regulate the immune system, and could affect type-1 diabetes and multiple sclerosis. Abnormal mitochondria link to neurodegeneration such as Alzheimer’s and Parkinson’s.
Unlike the blood, the brain and heart contain cells that don’t replicate, Verdin said. “You might have mitochondria for 20 years” without it being refreshed, he said. “These mitochondria tend to get clogged up. Sirtuins help maintain them in a pristine state.”
He studies nicotinamide adenine dinucleotide, a coenzyme found in cells that affects metabolism and aging. “It’s used by sirtuins in cells,” he said. Verdin takes nicotinamide riboside, a recently discovered form of vitamin B3 that functions as a precursor to NAD. “A lot of people in the aging field take it,” he said. “It has a very low level of toxicity.”
“Nicotinamide riboside is available in selected foods and possibly available to humans by supplements,” according to an abstract in the National Institutes of Health. “It has properties that are insulin-sensitizing, enhancing to exercise, resisting to negative effects of high-fat diet and neuroprotecting.”
Verdin’s research on proteins called histone deacetylases, which allow DNA to wrap more tightly inside cells, could lead to breakthroughs affecting the immune system and aging process. He plans to set up a lab at Buck and continue his research, with about 15 employees.
Another area of research interest involves ketone bodies, generated by the body during fasting and exercise. “They are a form of energy,” he said, as well as signaling molecules, with possible anti-aging effects. “The brain cannot burn fat. It needs either carbohydrates or ketone bodies.” A ketogenic diet, high in fat with adequate protein and low carbohydrates, forces the body to burn fat rather than carbohydrates. Mice on such a diet live longer and enjoy better cognition, demonstrated by their performance on a water-maze test. They also resist a form of Alzheimer’s.
Sirtuins may be stimulated by resveratrol, an ingredient in red wine, as well as by calorie restriction.
In 2013, GlaxoSmithKline shut down Sirtris, a sirtuin-research company it bought five years earlier for $720 million, and integrated Sirtris into Glaxo’s R&D. Its SRT2104 compound, designed to activate sirtuins, was aimed at diabetes and ulcerative colitis. Verdin served on the scientific advisory board of Sirtris/GSK.
The Buck’s 25-member board has business leaders, including: Larry Rosenberger, chairman, former president and CEO, Fair Isaac; Charles M. Stockholm, former chairman, Citibank International; Roy Eisenhardt, former president of Oakland A’s baseball team; Charles La Follette, president of La Follette Capital and former board member, Pacific Stock Exchange; and Richard Rosenberg, former chairman and CEO, Bank of America. Rosenberg was among donors on the Buck board who brought in $11 million in pledges, announced in November.
The $11 million will be used for “relaunching us,” Verdin said, “Buck acceleration.” He aims to continue the effort to reach $15 million. “We’re going to need more,” he said. “We need to be more nimble in how we look at revenue sources,” adopting a model more like a business. Gladstone used such a model successfully, he said.
Former CEO Kennedy was criticized by some faculty members when he sought financial support from board members with ties to the Middle East, and for perceived conflicts of interest.
“Every place has to manage the interface of science and commercial interest,” Verdin said. “As scientists, we struggle.”
“The fundraising approach was based on building an international network of donors” under Kennedy, Verdin said. “It worked to some degree, but not to the degree they were hoping.” Verdin plans to refocus fundraising efforts locally, including sources in Marin, San Francisco and the Bay Area. “I want Marin to know that they have a gem,” he said.
“I see the promise in this field,” he said. “It’s palpable, ready to burst. I want us to be at the leading edge of the next stage” of aging research, where science is translated into clinical results. “That’s why I took the job. This place could be incredible. Calico is a huge player in the field. Google puts its might behind an effort and they choose to be here. It’s a form of validation,” he said.
“We also have Unity. These are two of the biggest players in aging research in the Bay Area. I want every aging company in the Bay Area to think this is the place to be, the aging hub.”
Buck grant money was declining, he said. There are now 18 faculty members.
“We would love to hire two or three new groups” of researchers then support them for two or three years until they can obtain grants. NIH grants brought the Buck about $18 million last year. Philanthropy accounted for $7 million. Leasing is about $3 million. Corporate-sponsored research is another source of revenue.
There is land on which to build two more buildings, already approved by the county of Marin. That could take $50 million.
“The last 20 years have seen a complete change in the way we think about aging,” Verdin said. He predicts eventual change in the medical field. “You need to understand what a patient is,” he said, and he plans to help non-medical scientists with this shift to medical relevance. “What are the needs in a clinic? I want us to be disruptors. We will soon be embraced,” he said.
“They are very happy fighting one disease at a time,” he said about big pharmaceutical companies that make billions of dollars in revenue from drugs used to manage symptoms of diseases of aging.
“If you think about risk factors for disease, age is the strongest risk factor,” he said. “The revolution is the realization that we can control the rate of aging. You can flip a gene and aging slows down. You can find small molecules that control the rate of aging. The beauty when you do this is you affect all the conditions for which age was a risk factor in one move.”
James Dunn covers technology, biotech, law, the food industry, and banking and finance. Reach him at firstname.lastname@example.org or 707-521-4257