Impact of IL-11 on Mitochondrial Fitness and Skin Inflammation Associated with Aging

• Grant number: 25/01495-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2025
• End date: March 31, 2029
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Anthony Gabry da Silveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/07482-2 - Sensing extra and intracellular stressors by renal and immune cells: new insights into signal reception and transduction, and their relevance for understanding renal diseases, AP.TEM

Abstract

The skin plays essential roles for the body, including acting as a protective barrier and providing immune surveillance. Its aging is marked by structural and functional changes that lead to metabolic and phenotypic alterations. An important aspect of this process is cellular senescence, where cells secrete factors from the senescence-associated secretory phenotype (SASP), including pro-inflammatory cytokines that contribute to low-grade chronic inflammation. Recent studies have shown that inhibition of interleukin-11 (IL-11) in mice increases lifespan and health quality. Although the skin was not the main focus of this research, a decrease in fur loss was observed in aged mice with deletion of IL-11 and its receptor, suggesting preservation of epidermal stem cell functionality. However, the role of IL-11 in these cells and in mature keratinocytes, as well as its influence on skin immunobiology and aging, still needs further exploration. Aging is also characterized by a decline in cellular metabolic functionality. Inhibition of IL-11 promotes metabolic improvement, indicating an interconnection between inflammation, senescence, and mitochondrial dysfunction. Despite these observations, the specific role of mitochondria in these processes and how IL-11 signaling impacts mitochondrial fitness remains to be better understood. Thus, in this project, we aim to investigate the hypothesis that IL-11 inhibition may promote mitochondrial fitness in aged skin, resulting in better outcomes regarding inflammation associated with aging.