What Are the Most Crucial Questions Facing Aging Research?

Joining host Dr. Robert Hughes today on this inaugural episode of Translating Aging is our distinguished guest, Dr. Eric Verdin. Dr. Verdin is the president and CEO of the Buck Institute for Research on Aging, where his research primarily focuses on the relationship between aging and the immune system, and how immune aging is regulated by nutrition. He is also a Professor of Medicine at UCSF.

Dr. Verdin begins by sharing his medical background, including his early research on HIV transcription and what drew him to the field of aging. He discusses NAD Metabolism, its connection to the regulation of sirtuins, and his research on why NAD levels decrease during aging, which has a deleterious effect on a variety of organs. Dr. Verdin answers questions about whether NAD supplementation could be helpful in fighting aging and disease, the emergence of startup companies in the Bay Area that are attempting to address aging directly, and the challenges of conducting research on aging when it is not yet defined as a disease. He talks about establishing the world’s first Center for Female Reproductive Longevity and Equality after being approached by Nicole Shanahan (wife of Sergey Brin) about the connection between early infertility and the aging process. In addition, Dr. Verdin explains why the link between health span and life span may be more connected than we think, whether we can ever reach a life expectancy of 115 years or more in humans, and why he believes this period in time will later be viewed as the birth of a whole new age of biology and health.

To learn more about Dr. Eric Verdin, the Buck Institute, and their cutting-edge research to help people live better longer, visit BuckInstitute.org.

Episode Highlights:

• Dr. Eric Verdin’s professional background, medical education and experience
• Background in virology and evolution to field of aging
• His work studying HIV transcription led to research on biology of aging
• Most compelling questions facing aging research 
• Molecular study of aging as a field is less than 30 years old
• Number of hallmarks of aging seem to be happening independently of each other and we do not yet have a sense of the hierarchy of these hallmarks
• Chronic inflammation is a key aspect of the aging process, but was not listed in that collection of hallmarks
• Developing a better understanding of the different manifestations of aging and how they are related
• Working on one aspect of aging influences the other
• NAD Metabolism and its connection to the regulation of sirtuins 
• Decrease in NAD levels with age has deleterious consequences on a variety of organs
• Salvage pathway, CD38 Molecule, and PARP1 may play a role
• Diseases that involve chronic DNA damage and NAD depletion offer insight
• NAD supplementation to help fight against aging and disease
• NAD precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have been shown to alleviate some of the complications associated with aging in animal models 
• Questions about whether these supplements will be truly and rigorously tested to ensure efficacy
• Emergence of other startups that are focusing on aging research has created a number of amazing opportunities for translation - studying the process in humans and molecular pathways in particular
• Dr. Verdin has helped launch startup companies Napa Therapeutics and BHB Therapeutics
• Challenge that aging itself is not recognized as disease and how this impacts the ability to conduct clinical research on it
• Example of Unity Biotechnology, which targets cellular senescence
• Alternative idea is to identify a series of novel indications that are clearly linked to aging, such as Frailty and Sarcopenia
• Novartis demonstrated that pretreatment with rapamycin increased response to influenza vaccines
• Reproductive senescence, and link between early infertility and aging
• Nicole Shanahan has funded the Center for Female Reproductive Longevity and Equality at the Buck Institute for the first five years
• Goal is to increase female reproductive longevity
• Health span versus life span
• Centenarians not only live longer than most of us, but they spend less time being sick over their lifetime as well (5% versus 15%)
• Compressed morbidity and whether average life expectancy will ever reach 115 years or more
• Exciting collaborations and innovative research on the horizon for the Buck Institute

Quotes:

“I think one of the great privileges of being a basic scientist is that you can essentially study whatever you want. And I have a lot of interests and a lot of curiosity.”

“I just found it an irresistible topic to study.”

“One of the things that really drew me to the field is this realization that this is a field where fundamental questions still remain to be answered.”

“One of the things that fascinates me is really the idea of establishing clearer links between these hallmarks of aging and hopefully somewhat of a more unified theory of aging.”

“No one really believes there is a single cause of aging.”

“What is happening during aging is that NAD levels decrease, and that has been documented in a variety of organs.”

“Given the fact that NAD levels are decreasing, there’s been an interest in trying to restore these NAD levels. And one way to do this is two potential precursors to NAD: One called nicotinamide riboside (NR) and the other one called nicotinamide mononucleotide (NMN). Both of these have been explored in the literature and in humans, and both of those actually restore NAD levels to some degree.”

“These companies are just two examples of a whole ecosystem that is rapidly developing in the Bay Area.”

“The way that most companies have decided to tackle the problem is to actually use the knowledge of aging and its pathways to target really unique indications.”

“The hope is that once you have identified a drug that targets senescence, for example, in the knee, is that the same molecule could be used for further indications where senescence is also prevalent.”

“As a physician, there is a part of me that resists the idea of calling aging a disease, but clearly aging itself is a risk factor for a whole series of diseases.”

“It turns out, at least in many of the animal model systems in which we can increase life span, we also increase health span.”

“Our life span is going to continue to increase, and I think our major goal is really to make sure that these gained years actually are quality years, spent with people who are fully in command of their mental and physical abilities.”

“I’m incredibly optimistic of what we’re going to be doing in the future, but also I think we should be realistic about the difficulties that lie on this path.”

“I think it’s an incredible time to be in this field, and I suspect that when we look back 20 or 30 years from now, we will really look at his period as the birth of a whole new age of biology and health.”

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