The Impact Circle provides a “behind the scenes” view of Buck science for a unique and engaging experience for participating donors. It is an exciting opportunity for supporters to meet with brilliant scientists and to immerse themselves in the cutting-edge research underway at the Institute. Each year, Impact Circle members are presented with pitches from one or more labs for “Blue Sky” projects that require seed funding to get off the ground. Typically, these are collaborations among multiple faculty and fellows that are at too early a stage to qualify for a government grant. Scientists, incentivized by this support, dig deep for their most novel and innovative idea, gathering their lab members to distill the science behind those ideas into accessible and exciting projects for Circle Members.
REGISTER for the upcoming Impact Circle event on May 18, 2023.
Donors join the Impact Circle by making a $5000 contribution. That investment serves as seed funding or a “kickstarter” to launch one or more groundbreaking research projects chosen by Impact Circle Members. Membership in the Impact Circle is an easy and exciting way to explore and discover right alongside Buck scientists.
If you have a Donor Advised Fund (DAF), recommending a grant to the Impact Circle is an easy and simple way to participate. Click here to find out more.
Impact Circle Details
Buck’s first human clinical trial to study the effects of nutritional ketones on aging
The Potential Impact:
This is the first clinical research that attempts to directly link nutritional ketosis to aging biomarkers. Whilst the study is also collecting measures of safety, tolerability, physical function, cognitive function and quality of life, the addition of these geroscience biomarkers will provide crucial mechanistic insight into how ketone bodies effect aging in humans.
The Buck Institute for Research on Aging has launched its first human clinical trial. The BIKE (Buck Institute Ketone Ester) pilot study is the first trial in the world to look at the effects of ketone ester supplementation in the context of aging. Thirty healthy individuals over the age of 65 will take part in a 12-week double-blind, randomized, placebo-controlled study to see whether benefits of ketone bodies in aging that have been observed in mice translate to human beings.
Vulnerability and Resilience in the Brain: The cellular response to toxic proteins in aging and age-related dementia
The 2021 Impact Circle project was an innovative and collaborative research project designed to discover how normal aging, together with the harmful accumulation of toxic proteins associated with Alzheimer’s Disease and others, negatively impact healthy brain cells and to identify possible new treatments and interventions.
Millions of people are suffering from progressively debilitating dementia as they age, and the number of people diagnosed with Alzheimer’s disease (AD) is steadily rising. The risk of developing neurodegenerative disorders such as AD and dementia increases with age, and these conditions often require specialized care and treatment. The increasing demand for these services places a large strain on our healthcare system and can have a devastating impact on the lives of these individuals and their families.
Cutting-edge research can make a huge impact on those living with neurodegenerative disorders and helps us to realize our vision of developing therapies to not only prevent these diseases in the future, but also keep our brains young and healthy.
“It is becoming obvious that intervening early in the disease process is essential in order to promote healthy aging of the brain. My lab is focused on discovering how the brain can be resilient to the onset of age-related memory loss. I am interested in establishing a body of work in the area of brain resiliency in human clinical settings. This research may uncover new approaches for therapeutic intervention.”
“Proteins are the building blocks and functional units of life. Loss of protein function leads to physiological degeneration and age-related diseases. Protein function depends on its 3D shape and localization inside the cell. My lab focuses on understanding age-related defects in protein 3D shape and localization as an essential component of efforts to understand and intervene in age-related disease. I am currently a Buck Fellow and a recipient of the NIH Director’s Early Independence Award, a competitive early career award from NIH (1 of the 10 awardees nationwide). Funding for this project will accelerate my career in this exciting area of research and open up new avenues of innovation that are otherwise impossible.”
The project brought together two labs with individual areas of expertise to go beyond what we would be able to do independently from each lab, and will used a collaborative approach that is unique to the Buck. They utilized a new imaging screen technology that will revolutionize mechanistic studies on AD by studying the toxicity and resilient factors towards AD-related protein aggregates in aged cells. This project opened up a new dimension for us to understand for the first time how normal aging, together with AD-related toxic protein aggregations, damage the protein localization and function in a cell. The study provides unprecedented insight into how the human brain can be resilient to the memory loss caused by age-related toxic proteins. Uncovering the mechanisms that underlie cellular vulnerability and resilience in brain aging and AD will allow us to explore new strategies to prevent or treat dementia.
What is the impact of the Impact Circle? Our donors come back, year after year, anxious to learn and participate. And our scientists are raring to go every year because, it turns out that the Impact Circle has provided a lot of bang for the Buck scientist.
Up-ending the Scientific Status Quo
The first winners of the Impact Circle, Judy Campisi and Julie Andersen, used their funding to carve out entirely new scientific territory. Campisi is the world’s leading authority on cellular senescence – the process by which cells cease to divide, then accumulate and secrete toxins – and its role in aging. Yet she had never considered that cellular senescence might happen in the brain because most neurons do not divide to begin with. Andersen, a neuroscientist renowned for her expertise in Parkinson’s disease (PD), proposed that they investigate whether cellular senescence occurs in the brain and, if so, whether it is linked to PD.
“We had submitted grants on the topic to the NIH and got rejected again and again,” recalls Andersen. “I assume it was because people in the aging field knew of cellular senescence, but people in neuroscience had no idea what it was.” Now they do, thanks, in part, to the Impact Circle. Andersen and Campisi were able to initiate experiments with the money from the Impact Circle. The results from those experiments led to more funding from the NIH and then from the Michael J. Fox Foundation. “Basically, all that work ended up in Cell Reports in January of 2018 as the first paper to show that if you knocked out senescent cells in the brain, it prevented an age-related neurodegenerative disease – Parkinson’s,” says Andersen.
The Gift That Goes on Giving
Likewise, Pankaj Kapahi was recently awarded a National Institutes of Health (NIH) RO1 grant, one of the institute’s largest and most prestigious, for a study that combines all three of his Circle projects. With the grant, Kapahi is exploring why people with diabetes are at two times the risk of Alzheimer’s disease. He hypothesizes that the accumulation of advance glycation end products (AGEs) – toxic byproducts of glucose metabolism that are more prevalent in people with diabetes – are to blame for the neurodegeneration that develops.
“The Circle supported the preliminary work it took to get NIH funding,” says Kapahi. “Our NIH grant wouldn’t have been possible without it.” Circle funding has had a fundamental impact on his career. “The Impact Circle pushed my lab in a whole new direction,” adds Kapahi. Prior to his wins, his lab was focused primarily on dietary restriction. “This seed funding has helped us create more far-reaching connections with diseases like Parkinson’s,” he says.
Our Impact Circle, like all circles, is ongoing. Winners continually apprise Circle Members of their progress. Indeed, six months after Campisi and Andersen won, they got together with Circle members to celebrate and share their work. “It’s so nice to be able to interact with people on a personal level about your work,” says Andersen. “The Circle Members have been so supportive and it is really so nice knowing that they believe in us.”
2022 John Newman and Brianna Stubbs
2021 Tara Tracy and Kai Zhou
2020 Dan Winer and David Furman
2019 Simon Melov and Nicolas Martin
2018 Pankaj Kapahi and Neelanjan Bose
2017 Jennifer Garrison and Birgit Schilling
2017 Pankaj Kapahi and John Newman
2016 Julie Andersen and Pankaj Kapahi
2015 Dale Bredesen and Brian Kennedy
2014 Judy Campisi and Julie Andersen
Blood brain barrier: The blood–brain barrier is a highly selective semipermeable border of endothelial cells that prevents toxins in the circulating blood from crossing into brain.
Glycation (sometimes called non-enzymatic glycosylation) is the attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, or their derivatives. Glycation is a biomarker for diabetes and is implicated in some diseases and in aging.
Human induced pluripotent stem (iPS) cells: are derived from skin or blood cells that have been reprogrammed back into an embryonic-like, undifferentiated state that enables the development of any type of human cell needed for therapeutic purposes. Shinya Yamanaka of the Gladstone Institute and UCSF, received a Nobel for discovering them. They have transformed biological research. iPS cells can be developed into organoids, which are miniaturized and simplified version of an organ produced in vitro in three dimensions that show realistic micro-anatomy. Organoids made from human tissues allow scientists to study the effectiveness of novel therapeutics in a safe, inobtrusive and precise way.
Intergenerational – existing or occurring between generations. Example: Research has shown the impact of polychlorinated biphenyls (PCBs) – chemicals that were used in electrical equipment starting in the 1920’s – across generations. Although they have been phased out of production, PCBs are still being released into the environment from preexisting applications and improper disposal of products that contain them. Because of their chemical stability and transportability, they accumulate in the food chain, enter our food supply, and pass from mother to infant in utero and during breastfeeding, with potentially harmful effects on the endocrine, immune, nervous, and reproductive systems.
Synapse – the space between two neurons where chemical substances are retained to transfer electrical signals from one neuron to another.
T-cells – is an immune cell, made in the bone marrow, that attacks virus-infected cells, foreign cells and cancer cells. The T in T-cells stands for thymus, an organ at the front of the trachea, where T-cells mature.
Tau – is a protein shaped like a tube that transports nutrients from one nerve cell to another. Damaged and misshapen tau are found in multiple forms of brain disease, including Alzheimer’s disease, chronic traumatic encephalopathy, Pick disease, frontotemporal dementia with parkinsonism-17, progressive supranuclear Palsy, and corticobasal degeneration.