Podcast: Should Scientific Controversies Be Silenced?
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
The recent Joe Rogan/Spotify controversy prompts the consideration of tough questions about expertise, trust, gatekeepers, and dissent.
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
The recent Joe Rogan/Spotify backlash over the misinformation presented in his recent episode on the Covid-19 vaccines raises some difficult and important bioethical questions for society: How can people know which experts to trust? What should big tech gatekeepers do about false claims promoted on their platforms? How should the scientific establishment respond to heterodox viewpoints from experts who disagree with the consensus? When is silencing of dissent merited, and when is it problematic? Journalist Kira Peikoff asks infectious disease physician and pandemic scholar Dr. Amesh Adalja to weigh in.
Dr. Amesh Adalja, Senior Scholar, Johns Hopkins Center for Health Security and an infectious disease physician
Listen to the Episode
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
The Cellular Secrets of “Young Blood” Are Starting to Be Unlocked
Fabrisia Ambrosio (center) surrounded by her lab staff.
The quest for an elixir to restore youthful health and vigor is common to most cultures and has prompted much scientific research. About a decade ago, Stanford scientists stitched together the blood circulatory systems of old and young mice in a practice called parabiosis. It seemed to rejuvenate the aged animals and spawned vampirish urban legends of Hollywood luminaries and tech billionaires paying big bucks for healthy young blood to put into their own aging arteries in the hope of reversing or at least forestalling the aging process.
It was “kind of creepy” and also inspiring to Fabrisia Ambrosio, then thousands of miles away and near the start of her own research career into the processes of aging. Her lab is at the University of Pittsburgh but on this cold January morning I am speaking with her via Zoom as she visits with family near her native Sao Paulo, Brazil. A gleaming white high rise condo and a lush tropical jungle split the view behind her, and the summer beach is just a few blocks away.
Ambrosio possesses the joy of a kid on Christmas morning who can't wait to see what’s inside the wrapping. “I’ve always had a love for research, my father was a physicist," she says, but interest in the human body pulled her toward biology as her education progressed in the U.S. and Canada.
Back in Pittsburgh, her lab first extended the work of others in aging by using the simpler process of injecting young blood into the tail vein of old mice and found that the skeletal muscles of the animals “displayed an enhanced capacity to regenerate.” But what was causing this improvement?
When Ambrosio injected old mice with young blood depleted of EVs, the regenerative effect practically disappeared.
The next step was to remove the extracellular vesicles (EVs) from blood. EVs are small particles of cells composed of a membrane and often a cargo inside that lipid envelope. Initially many scientists thought that EVs were simply taking out the garbage that cells no longer needed, but they would learn that one cell's trash could be another cell's treasure.
Metabolites, mRNA, and myriad other signaling molecules inside the EV can function as a complex network by which cells communicate with others both near and far. These cargoes can up and down-regulate gene expression, affecting cell activity and potentially the entire body. EVs are present in humans, the bacteria that live in and on us, even in plants; they likely communicate across all forms of life.
Being inside the EV membrane protects cargo from enzymes and other factors in the blood that can degrade it, says Kenneth Witwer, a researcher at Johns Hopkins University and program chair of the International Society for Extracellular Vesicles. The receptors on the surface of the EV provide clues to the type of cell from which it originated and the cell receptors to which it might later bind and affect.
When Ambrosio injected old mice with young blood depleted of EVs, the regenerative effect practically disappeared; purified EVs alone were enough to do the job. The team also looked at muscle cell gene expression after injections of saline, young blood, and EV-depleted young blood and found significant differences. She believes this means that the major effect of enhanced regenerative capacity was coming from the EVs, though free floating proteins within the blood may also contribute something to the effect.
One such protein, called klotho, is of great interest to researchers studying aging. The name was borrowed from the Fates of Greek mythology, which consists of three sisters; Klotho spins the thread of life that her sisters measure and cut. Ambrosio had earlier shown that supplementing klotho could enhance regenerative capacity in old animals. But as with most proteins, klotho is fragile, rapidly degrading in body fluids, or when frozen and thawed. She suspected that klotho could survive better as cargo enclosed within the membrane of an EV and shielded from degradation.
So she went looking for klotho inside the EVs they had isolated. Advanced imaging technology revealed that young EVs contained abundant levels of klotho mRNAs, but the number of those proteins was much lower in EVs from old mice. Ambrosio wrote in her most recent paper, published in December in Nature Aging. She also found that the stressors associated with aging reduced the communications capacity of EVs in muscle tissue and that could be only partially restored with young blood.
Researchers still don't understand how klotho functions at the cellular level, but they may not need to know that. Perhaps learning how to increase its production, or using synthetic biology to generate more copies of klotho mRNA, or adding cell receptors to better direct EVs to specific aging tissue will be sufficient to reap the anti-aging benefits.
“Very, very preliminary data from our lab has demonstrated that exercise may be altering klotho transcripts within aged extracellular vesicles" for the better Ambrosio teases. But we already know that exercise is good for us; understanding the cellular mechanism behind that isn't likely to provide additional motivation to get up off the couch. Many of us want a prescription, a pill that is easy to take, to slow our aging.
Ambrosio hopes that others will build upon the basic research from her lab, and that pharmaceutical companies will be able to translate and develop it into products that can pass through FDA review and help ameliorate the diseases of aging.
Scientists Are Studying How to Help Dogs Have Longer Lives, in a Bid to Further Our Own
Feeding dogs only once a day is showing health benefits in a large study, scientists report.
The sad eyes. The wagging tail. The frustrated whine. The excited bark. Dogs know how to get their owners to fork over the food more often.
The extra calories dogs get from feeding patterns now used by many Americans may not be good for them from a health and longevity viewpoint. In research from a large study called the Dog Aging Project, canines fed once a day had better scores on cognition tests and lower odds of developing diseases of organs throughout the body: intestinal tract, mouth and teeth, bones and joints, kidneys and bladder, and liver and pancreas.
Fewer than 1 in 10 dog owners fed their furry friends once daily, while nearly three fourths provided two daily meals.
“Most veterinarians have been led to believe that feeding dogs twice a day is optimal, but this is a relatively new idea that has developed over the past few decades with little supportive evidence from a health standpoint,” said Matt Kaeberlein, PhD, Co-Director of the Dog Aging Project, a professor of pathology and Director of the Healthy Aging and Longevity Research Institute at the University of Washington. Kaeberlein studies basic mechanisms of aging to find ways of extending the healthspan, the number of years of life lived free of disease. It’s not enough to extend the lifespan unless declines in biological function and risks of age-related diseases are also studied, he believes, hence the healthspan.
The Dog Aging Project is studying tens of thousands of dogs living with their owners in the real world, not a biology laboratory. The feeding study is the first of several reports now coming from the project based on owners’ annual reports of demographics, physical activity, environment, dog behavior, diet, medications and supplements, and health status. It has been posted on bioRxiv as it goes through peer review.
“All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans. It just happens much faster in dogs.”
“The Dog Aging Project is one of the most exciting in the longevity space,” said David A. Sinclair, professor in the Department of Genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. “Not only is it important to help our companions live longer and healthier, but because they are like people and share the same environment and many of the lifestyles as their owners, they are the perfect model for human longevity interventions.”
The epigenetic clock — and specifically changes in gene expression resulting from methylation of cytosine and guanine in the DNA — provides the critical connection between aging in dogs and people. “All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans,” Kaeberlein said. “It just happens much faster in dogs.” These methylation changes, called the “methylomes,” have been associated with rates of aging in dogs, humans, and also mice.
In a 2020 study young dogs matched with young adults and aged dogs matched with older adults showed the greatest similarities in methylomes. In the Cell Systems report, Tina Wang of the University of California, San Diego, and colleagues wrote that the methylome “can be used to quantitatively translate the age-related physiology experienced by one organism (i.e., a model species like dog) to the age at which physiology in a second organism is most similar (i.e., a second model or humans).” This allows rates of aging in one species to be mapped onto aging in another species, providing “a compelling tool in the quest to understand aging and identify interventions for maximizing healthy lifespan.”
In the Dog Aging Project study, 8% of 24,238 owners fed their dogs once daily, the same as the percentage of owners serving three daily meals. Twice-daily feedings were most common (73%), and just over 1 in 10 owners (11%) “free fed” their dogs by just filling up the bowl whenever it was empty — most likely Rover’s favorite option.
“The notion of breakfast, lunch, and dinner for people in the United States is not based on large studies that compared three meals a day to two meals a day, or to four, “ said Kate E. Creevy, chief veterinary officer with the Dog Aging Project and associate professor at Texas A&M University. “It’s more about what we are accustomed to. Similarly, there are not large population studies comparing outcomes of dogs fed once, twice, or three times a day.”
“We do not recommend that people change their dogs’ diets based on this report,” Creevy emphasized. “It’s important to understand the difference between research that finds associations versus research that finds cause and effect.”
To establish cause and effect, the Dog Aging Project will follow their cohort over many years. Then, Creevy said, “We will be able to determine whether the associations we have found with feeding frequency are causes, or effects, or neither.”
While not yet actionable, the feeding findings fit with biology across a variety of animals, Kaeberlein said, including indicators that better health translates into longer healthspans. He said that caloric restriction and perhaps time-restricted eating or intermittent fasting — all ways that some human diets are structured — can have a positive impact on the biology of aging by allowing the gastrointestinal tract to have time each day to rest and repair itself, just as sleep benefits the brain through rest.
Timing of meals is also related to the concept of ketogenesis, Kaeberlein explained. Without access to glucose, animals switch over to a ketogenic state in which back-up systems produce energy through metabolic pathways that generate ketones. Mice go into this state very quickly, after a few hours or an overnight fast, while people shift to ketogenesis more slowly, from a few hours to up to 36 hours for people on typical Western diets, Kaeberlein said.
Dogs are different. They take at least two days to shift to ketogenesis, suggesting they have evolved to need fewer meals that are spaced out rather than the multiple daily meals plus snacks that people prefer.
As this relates to longevity, Kaeberlein said that a couple of studies show that mice who are fed a ketogenic diet have longer lifespans (years of life regardless of health). “For us, the next step is to analyze the composition of the dogs’ diets or the relationship of multiple daily feedings with obesity,” he said. “Maybe not being obese is related to better health.”
To learn more, the Dog Aging Project needs dogs — lots of dogs! Kaeberlein wants at least 100,000 dogs, including small dogs, large dogs, dogs of all ages. Puppies are needed for the researchers to follow across their lifespan. The project has an excellent website where owners can volunteer to participate.
Nutritional strategies are often not built around sound scientific principles, Kaeberlein said. In human nutrition, people have tried all kinds of diets over the years, including some that were completely wrong. Kaeberlein and his colleagues in the Dog Aging Project want to change that, at least for people’s canine companions, and hopefully, as a result, give dogs added years of healthy life and provide clues for human nutrition.
After that, maybe they can do something about those sad eyes and the frustrated whine.