Latest News on Aging Research from the U - a Discussion with Dr. Paul Robbins

Article by Becky Fillinger, photo provided

Dr. Robbins is a resident of the Mill District, but more importantly, he is Professor of Biochemistry, Molecular Biology and Biophysics and Associate Director of the Institute on the Biology of Aging and Metabolism (iBAM) and the Medical Discovery Team on the Biology of Aging at the University of Minnesota. We talked to him about Geroscience and senescent cells and expanding our healthspan because – well - we’re all aging! 

Dr. Paul RobbinsQ:  Please tell us the definition of Geroscience.

A:  Geroscience is the concept that the biggest risk factor for diseases that come with old age is the aging process itself. What we have done with healthcare forever is target one disease at a time. What leads to an increased risk of diabetes, cancer, heart disease, dementia – almost every disease you can name – is aging itself. We need to not target each disease, which leads a handful of different pills, but rather target aging itself. It goes across all disease fronts. We should be focusing on aging to treat or prevent or reduce the severity of all these different diseases.

Q:  Please tell us about senescent cells and why the U is interested in slowing or reversing their damage to the body?

A:  Some years ago, all the aging researchers got together and came up with the hallmarks of aging – things that go wrong with aging. Also, the hallmarks are interconnected so if you could target one of the hallmarks, other hallmarks should improve too, providing a therapeutic benefit to the patient. There are many of these – mitochondria go bad, your stem cells don’t work as efficiently, chronic inflammation, etc. But one of the hallmarks that happens and has been documented extensively is that as cells acquire damage (which can happen through many different ways) they trigger a cell fate called senescence where the damaged cells shut down. Senescent cells stop growing and release inflammatory factors that instruct your immune system to get rid of them. If your immune system is healthy, it will recognize the cells as damaged – the cells are killed and removed from our bodies. But as we age and our immune system starts to fail, these damaged cells are not removed from the body as efficiently. They’re not cleared and it leads to chronic inflammation, which leads to a variety of adverse health conditions. We’ve shown in animal models that if you clear or remove the senescent cells, (using genetic tricks in mice and we’ve developed senolytic drugs that in mice work effectively) mice live healthier and with a 10-20% increased lifespan. The goal is compressing the period of co-morbidity. We’ve observed that people are healthy for a number of years and then everything starts to fall apart. In that slope where things continue to go wrong – the gradual decay – it leads to nursing homes, increased medical care, etc. We are trying to compress that period of decline to keep someone healthier longer. Increasing the healthspan is our goal. We would like to mimic in humans what we’re seeing in mice. 

Q:  How important is interdisciplinary collaboration in your research on senescent cells?

A:  It is absolutely essential. One of the things we were tasked with when we came here was to encourage all researchers to include aging as a variable in their research. We collaborate across campus and all over the country – some you would not expect. If you think about cancer or heart disease, it takes many people and specialties to treat the diseases, with aging as a primary cause of the diseases. An advantage of being at the U is that it is a large university with a large medical school, and they have departments and institutes and centers working in almost every health area. So, for example we work with neuroscientists because Alzheimer’s and dementia are associated with aging. Cancer is absolutely a disease of aging (pediatric cancer aside); the biggest risk for breast and prostate cancer is aging. So, we work with the Cancer Center.  Transplants is another hot area. If you take a liver from a 70-year-old – the senolytics could improve the quality of the liver for the recipient. Also, the Covid pandemic showed the increased mortality of the elderly to viral infection so we are working with the Center for Immunology to increase resilience to pathogens in our aging population. Everyone is interested in aging now. 

The collaboration extends off campus as well. We are collaborating with people with funding from NASA.  Mars astronauts are going to be exposed to a lot of radiation. Damage from radiation leads to cellular senescence. We are sending cells to a laboratory in New York which can radiate them with space radiation.  We’re screening drugs to see which ones work against space-induced senescence. 

Q:  Are you conducting trials for your senolytics?

A:  Yes. Doing trials for aging is difficult – they’re expensive with many moving parts, for example, getting FDA approval to use the drugs on humans that have been used on mice is time consuming but must be done. There is one trial underway at the U for sepsis - they’re testing some of our senolytics for sepsis. Our trial is investigating whether you can reduce time in the hospital and mortality if you treat these people early on with these compounds we’ve developed to clear senescent cells. There’s one with the VA for obesity to see if our compounds can limit weight gain similar to a drug like Ozempic for which we are applying for funding.

We are also part of a national Translational Geroscience Network - 14 universities across the country with more than 40 trials underway for aging and age-related diseases. I’m on the steering committee of the network; the hope is that we will soon have many more clinical trials here at the U using the resources of the network.

Q:  Are there any foods that can reduce senescent cells?

A:  Yes, but you would have to eat a large amount of the foods to make a difference. One of the natural products is flavonoid found in strawberries called fisetin. There is evidence that people in other parts of the world who eat a lot of foods with fisetin are healthier. Is it the fisetin or is it something else? We don’t know.  It’s a natural product that is safe. Getting natural products into a clinical trial is easier. I take a fisetin supplement every couple of weeks. There is a clinical trial in Germany supported by the strawberry growers in Germany - they make a rich strawberry paste. We haven’t tested it here. There is much that we can learn about the foods we eat if we can test them on the hallmarks of aging.

Q:  How may we follow your news?

A:  Please check out our website: The Institute on the Biology of Aging and Metabolism. Here you’ll find our news listed and also podcasts and links to papers with the latest research.