Researcher Spotlight: Cristina Aguayo, PhD – Joslin Diabetes Center

July 7th, 2025 – MIAMI LAKES – For the past 30 years, Biorep has been working closely with scientists and researchers around the world to learn more about their research and inspiration. Today, we are pleased to share with you our latest interview with Cristina Aguayo-Mazzucato, PhD.  

 Dr. Aguayo-Mazzucato is a Principal Investigator at Joslin Diabetes Center in Boston, MA. She also serves as an Assistant Professor and Faculty Council to the Dean at Harvard Medical School. At Joslin, she works with a team in the Beta Cell Aging Lab including Christopher Cahill; Kanako Iwasaki, MD, PhD; Sandra Le, BS; Briana Cortez, BS and Idris Syed.  

Please tell us about your background and how you became a leading researcher at Joslin Diabetes Center?  

I was born in Barcelona, Spain, and received an MD degree in General Medicine and a PhD in Biomedical Sciences from the National Autonomous University in Mexico (UNAM). In 2007, I joined Prof. Susan Bonner-Weir's laboratory at Joslin Diabetes Center as a postdoctoral fellow. During this period, we studied beta-cell functional development and strategized ways to enhance functional maturity in vitro for cellular replacement therapies for diabetes.  

In July 2019, I established the Beta Cell Aging Lab at Joslin Diabetes Center with the aim of understanding how beta cells age, both physiologically and pathologically and whether this process contributes to the development of Diabetes. Our ultimate goal is to identify strategies that target these processes and have a positive impact in the prevention and treatment of the disease. 

What type of research is being pursued in the Beta Cell Aging Lab?  

Our work aims to elucidate the mechanisms of β-cell senescence, an aging hallmark, as a contributor to type 2 diabetes (T2D) and identify optimal therapeutic targets. Pancreatic insulin secreting β-cells, crucial to glucose homeostasis, are heavily secretory cells, equipped to respond to small changes in blood glucose levels and highly susceptible to stress by nutrient overload. Our work has identified that mouse and human β-cells undergo senescence in response to insulin resistance (IR), leading to loss of cellular identity, impaired function and secretion of a unique senescence-associated secretory phenotype (SASP). Additionally, we showed that targeting senescent cells improved blood glucose levels and recovery of β-cell function and identity. Our working hypothesis is that cellular senescence and its SASP are targetable drivers of β-cell dysfunction and loss. 

 Why have you chosen to focus on preventing, treating and curing diabetes?  

During my Medical Internship year, I realized the toll that diabetes has on patients and their families and what a huge opportunity it was to study and find new targets and pathways that could alleviate some of this burden. Additionally, this is a disease that has a disproportionate toll on underserved populations around the world, therefore finding therapeutic targets at earlier points during disease development could potentially alter its trajectory and societal toll.  

 What is senescence and how does it affect Type 1 and Type 2 diabetes? 

 Senescence is considered as one of the Hallmarks of Aging, and some cells in the body become senescent in response to age and/or stress. At the level of beta cells, this might lead to a loss of function and identity, resulting in an impaired response to glucose and nutrients. 

Although the mechanisms underlying senescence are different in Type 1 and Type 2 diabetes, they can both be targeted to rescue cell function and improve the capacity of the body to handle nutrients.  

 What are the biggest challenges facing your research and the islet biology field as a whole? 

As a field, we are fortunate to have a battery of very effective therapies that can control blood glucose levels through different mechanisms. And yet, there are still opportunities to uncover new pathophysiological processes in the aims of developing personalized therapies that are directed at specific pathways in each individual.  

 How has the PERI-LITE impacted your research?  

 Beta cell function is one of the main outcomes by which we measure the effects of senescence on cells and evaluate therapeutic interventions. Therefore, having the PERI-LITE has allowed us to measure this process dynamically, incorporating variables of time of response (beyond only magnitude) of cells to secretory stimuli. Additionally, we are also able to measure function from islets in pancreatic slices- this is a powerful tool since the cell environment is preserved and its effect on function can also be evaluated. 

In summary, it has brought us closer to predicting the impact of our studies under more physiological conditions. 

 What labs do you collaborate with and how do they positively impact your research? 

 We are very fortunate to collaborate with many researchers and laboratories, both at Joslin Diabetes Center and elsewhere. In terms of the perifusion studies, it is relevant to mention the KAPP-Sen Tissue Mapping Center, part of the SenNET NIH Consortium, which aims to map and study senescent cells in organs in the human body. By integrating spatial transcriptomics and proteomics with functional studies, our understanding of human biology is greatly enhanced.  

 What are your upcoming projects?  

 There is still a lot to learn about the aging process of beta cells, how they senesce, and which are the best interventions to recover their function and identity. As a group, we are always thinking of ways to bridge our findings into applicable interventions in the clinic. We hope to continue doing this work for a very long time. 

 And a fun question: If you had a magic wand to design any experiment without worrying about time, money or logistics, what experiment would you pursue?  

 A lot!  A few examples include: 1. find circulating biomarkers of senescent and non-senescent beta cells; 2. develop beta-cell specific therapies that can act and reprogram senescent cells; 3. perhaps even developing a vaccine that targets dysfunctional beta cells.  

 If people want to learn more about Dr. Aguayo-Mazzucato and her team, you can find them at https://www.betacellaginglab.com.

You can read more about her research in the papers linked below. 

 Carapeto P, Iwasaki K, Hela F, Kahng J, Alves-Wagner AB, Middelbeek RJW, Hirshman MF, Rutter GA, Goodyear LJ, Aguayo-Mazzucato C. Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence. Nat Metab. 2024 Oct;6(10):1976-1990. doi: 10.1038/s42255-024-01130-8. Epub 2024 Sep 24. PMID: 39317751. 

 Suryadevara V, Hudgins AD, Rajesh A, Pappalardo A, Karpova A, Dey AK, Hertzel A, Agudelo A, Rocha A, Soygur B, Schilling B, Carver CM, Aguayo-Mazzucato C, Baker DJ, Bernlohr DA, Jurk D, Mangarova DB, Quardokus EM, Enninga EAL, Schmidt EL, Chen F, Duncan FE, Cambuli F, Kaur G, Kuchel GA, Lee G, Daldrup-Link HE, Martini H, Phatnani H, Al-Naggar IM, Rahman I, Nie J, Passos JF, Silverstein JC, Campisi J, Wang J, Iwasaki K, Barbosa K, Metis K, Nernekli K, Niedernhofer LJ, Ding L, Wang L, Adams LC, Ruiyang L, Doolittle ML, Teneche MG, Schafer MJ, Xu M, Hajipour M, Boroumand M, Basisty N, Sloan N, Slavov N, Kuksenko O, Robson P, Gomez PT, Vasilikos P, Adams PD, Carapeto P, Zhu Q, Ramasamy R, Perez-Lorenzo R, Fan R, Dong R, Montgomery RR, Shaikh S, Vickovic S, Yin S, Kang S, Suvakov S, Khosla S, Garovic VD, Menon V, Xu Y, Song Y, Suh Y, Dou Z, Neretti N. SenNet recommendations for detecting senescent cells in different tissues. Nat Rev Mol Cell Biol. 2024 Dec;25(12):1001-1023. doi: 10.1038/s41580-024-00738-8. Epub 2024 Jun 3. PMID: 38831121; PMCID: PMC11578798. 

 Cortez BN, Pan H, Hinthorn S, Sun H, Neretti N, Gloyn AL, Aguayo-Mazzucato C. Heterogeneity of increased biological age in type 2 diabetes correlates with differential tissue DNA methylation, biological variables, and pharmacological treatments. Geroscience. 2024 Apr;46(2):2441-2461. doi: 10.1007/s11357-023-01009-8. Epub 2023 Nov 21. PMID: 37987887; PMCID: PMC10828255. 

 Midha A, Pan H, Abarca C, Andle J, Carapeto P, Bonner-Weir S, Aguayo-Mazzucato C. Unique Human and Mouse β-Cell Senescence-Associated Secretory Phenotype (SASP) Reveal Conserved Signaling Pathways and Heterogeneous Factors. Diabetes. 2021 May;70(5):1098-1116. doi: 10.2337/db20-0553. Epub 2021 Mar 5. PMID: 33674410; PMCID: PMC8173799. 

 Aguayo-Mazzucato C, Andle J, Lee TB Jr, Midha A, Talemal L, Chipashvili V, Hollister-Lock J, van Deursen J, Weir G, Bonner-Weir S. Acceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes. Cell Metab. 2019 Jul 2;30(1):129-142.e4. doi: 10.1016/j.cmet.2019.05.006. Epub 2019 May 30. PMID: 31155496; PMCID: PMC6610720. 

 Aguayo-Mazzucato C, van Haaren M, Mruk M, Lee TB Jr, Crawford C, Hollister-Lock J, Sullivan BA, Johnson JW, Ebrahimi A, Dreyfuss JM, Van Deursen J, Weir GC, Bonner-Weir S. β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance. Cell Metab. 2017 Apr 4;25(4):898-910.e5. doi: 10.1016/j.cmet.2017.03.015. PMID: 28380379; PMCID: PMC5471618.