This episode of Longevity by Design discusses topics related to regenerative medicine—senescent cells, biomaterials, arthritis, immunology, and more.
In this episode of Longevity by Design, our hosts, Dr. Gil Blander and Ashley Reaver, MS, RD, CSSD, are joined by Dr. Jennifer Elisseeff. Dr. Elisseeff holds a PhD in Medical Engineering and has conducted many interesting studies relating to tissue engineering and the immune system. Tune in as Dr. Elisseeff discusses the latest science in the field.
Meet Longevity by Design’s podcast guest, Dr. Jennifer Elisseeff
Dr. Jennifer Elisseeff is a professor of orthopedic surgery and director of the Translational Tissue Engineering Center at the Johns Hopkins School of Medicine. Dr. Elisseeff holds a PhD in Medical Engineering from the Harvard-MIT Division of Health Sciences and Technology. Her research interests include using stem cells for tissue engineering, regenerative medicine, aging, cornea repair, and cartilage regeneration. More specifically, Dr. Elisseeff is examining hydrogels as a scaffold for tissue engineering and is working to develop an artificial cornea.
The use of biomaterials
Dr. Elisseeff works closely with biomaterials, substances engineered to interact with biological systems for use in constructing artificial organs or replacing existing bone or tissue. Biomaterials were initially used simply as a substitute—for example, a hip, knee, or breast implant. In the early days of biomaterials, they were constructed to mimic the physical structure and some of the intended functions but were not integrated into one’s body. However, as the field of biomaterials has matured, biomaterials have developed into systems that actually interact with the body. “They stimulate tissue repair in addition to fixing the tissue physically,” explains Dr. Elisseeff. “They can be used to deliver drugs, improve wound healing, reduce scar formation, and potentially serve as a scaffold for local cells in the tissue.”
Biomaterials have tissue-specific responses, meaning the same biomaterial can react differently depending on where in the body it is placed. “We have seen that the same biomaterial can have different immune cells around it, depending on if it were adjacent to muscle or adipose tissue,” says Dr. Elisseeff. Additionally, the effectiveness of biomaterials is influenced by many factors, including the local tissue cells, interactions with the vascular blood supply, and the immune system. Dr. Elisseeff explains that when infection occurs in the body, the repair process is impeded, limiting the function of the biomaterial. She says that developing more sophisticated biomaterials with a coating to block infection will be important in the future.
The nuance of senescent cells
Healthy cells undergo controlled cellular division—meaning they divide when needed, a process that occurs millions of times per day. When cells in the body no longer divide but do not die, they are known as senescent cells. Senescent cells are studied for their impact on the aging process. They appear to accumulate with age, secrete inflammatory molecules onto nearby tissues, and are involved in several age-related pathologies.
However, senescent cells beneficially affect the body as well. "Senescent cells can communicate with immune cells and are important for wound healing," says Dr. Elisseeff. "We also see some senescence around vasculature and in fibrotic regions, and both of those different cell types are talking to the immune system as well. I see them almost as a byproduct for the systems' dysfunction with increased inflammation and then also the vasculature systems problems with aging."
Senescent cells are nuanced, and while recent discoveries in Dr. Elisseeff's lab show positive effects of senescent cells, her lab also studies their involvement in age-related diseases.
Senescent cells and age-related diseases
Dr. Elisseeff further discusses her lab's research on the association between senescent cells and age-related diseases. One of her team's first studies observed that cell senescence might be linked to arthritis, age-related joint swelling, or pain. "Similar to trauma to the skin or muscle, senescent cells develop when there is trauma to a joint. Unfortunately, in the joint, which doesn't have the same blood supply or ability to move cells and molecules, senescent cells accumulate and don't get removed," says Dr. Elisseeff. The accumulation of senescent cells can lead to chronic inflammation in the joints, which is characteristic of arthritis.
But as she mentioned earlier, senescent cells aren't all bad. Dr. Elisseeff and her team have also studied senescent cells in cancerous tumors. "There are certain tumor types that will not respond to immunotherapies, and in those tumors, we see senescent cells around the tumor independent of the tumor senescence itself. We see a different type of senescence in tumors that do respond to immunotherapy, and it has a wound-healing phenotype. For this reason, I think we can actually connect wound healing and tumor response to these therapies." Dr. Elisseeff concludes that as we unravel the roles of senescent cells, she expects new computational techniques to help identify them and understand their significance.
Osteoarthritis and senescent cells
Another research focus in Dr. Elisseeff's lab is osteoarthritis—specifically, how the immune system contributes to its development. Dr. Elisseeff explains that, traditionally, osteoarthritis was considered to be caused by "wear and tear" of the joints. For example, an avid runner may eventually get joint pain in their knee or hip, leading to osteoarthritis, making it challenging to continue running.
Although initially thought to be not involved with immunology, Dr. Elisseeff explains that osteoarthritis does interact with the immune system. "What we understand now with osteoarthritis is that in addition to the accumulation of senescent cells, at least in a model of post-traumatic osteoarthritis, is that there's also residual immune inflammation. It's not as inflamed or inflammatory as an autoimmune disease, but it's a low-level inflammation that over the tissue will degrade and can't repair itself."
Dr. Elisseef further discusses osteoarthritis, noting that it is a particularly tricky condition due to the vast diversity in how people experience cartilage damage and pain. For example, some people present with extreme cartilage damage but do not experience much pain, whereas others don't have much damage but can barely exercise because of their pain.
"So when, when you're designing a therapy in a clinical trial, what's your outcome? Is it reduced pain or reestablishing tissue structure? Or is it a combination of both?" She closes by reemphasizing that the diversity in people makes it challenging to do the clinical trials needed to get therapies approved for broader use.
To conclude the conversation on osteoarthritis, Dr. Elisseeff notes that regular exercise can help to improve this condition. "People used to think when you have cartilage problems like osteoarthritis; you should not exercise. However, recent studies show that movement actually helps. It promotes fluid exchange and can help get rid of inflammatory factors. I think it's important to keep us moving," she says. She elaborates that it is important to find a form of movement that doesn't cause high levels of pain and that diversity of exercise can help.
Advice on living a healthier longer life
Dr. Elisseeff shares her top tip for improving healthspan. “There are all these great studies on healthspan and longevity, and exercise is the only one that I see as having the most constant, reproducible, and most significant effect across the body.” She further emphasizes the importance of strength training—for both men and women—saying that maintaining muscle mass is a great way to promote healthy aging.