Granzyme B in aging and age-related pathologies

• Published in: Trends in molecular medicine
• Main Authors: Richardson, Katlyn C., Jung, Karen, Matsubara, Joanne A., Choy, Jonathan C., Granville, David J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 23.08.2024
• Subjects: aging; chronic disease; granzymes; impaired healing; inflammation; serine proteases; aging; granzymes; inflammation; chronic disease; serine proteases; impaired healing
• ISSN: 1471-4914; 1471-499X; 1471-499X
• DOI: 10.1016/j.molmed.2024.07.010

Granzymes are serine proteases with intracellular cytotoxic and/or proinflammatory functions but also accumulate in the extracellular space in aging and disease, promoting proinflammatory phenotypes through the cleavage of receptors, cytokines, adhesion molecules, and autoantigens.Granzyme B transcripts and protein have recently been detected in aging immune cell populations and linked to inflammaging phenotypes and age-related pathologies.Granzyme B has been implicated in many age-related pathologies.Granzyme B is induced by environmental factors that exacerbate biological aging (UV exposure, poor diet, smoking, wildfire smoke, grain dust), while genetic deletion and/or pharmacological inhibition of granzyme B reduces premature aging and/or disease phenotypes in animal models. Aging is a major risk factor for pathologies that manifest later in life. Much attention is devoted towards elucidating how prolonged environmental exposures and inflammation promote biological (accelerated) tissue aging. Granzymes, a family of serine proteases, are increasingly recognized for their emerging roles in biological aging and disease. Widely recognized as intracellular mediators of cell death, granzymes, particularly granzyme B (GzmB), also accumulate in the extracellular milieu of tissues with age, contributing to chronic tissue injury, inflammation, and impaired healing. Consequently, this has prompted the field to reconsider how GzmB regulation, accumulation, and proteolysis impact health and disease with age. While GzmB is observed in numerous age-related conditions, the current review focuses on mechanistic studies where proof-of-concept has been forwarded. Aging is a major risk factor for pathologies that manifest later in life. Much attention is devoted towards elucidating how prolonged environmental exposures and inflammation promote biological (accelerated) tissue aging. Granzymes, a family of serine proteases, are increasingly recognized for their emerging roles in biological aging and disease. Widely recognized as intracellular mediators of cell death, granzymes, particularly granzyme B (GzmB), also accumulate in the extracellular milieu of tissues with age, contributing to chronic tissue injury, inflammation, and impaired healing. Consequently, this has prompted the field to reconsider how GzmB regulation, accumulation, and proteolysis impact health and disease with age. While GzmB is observed in numerous age-related conditions, the current review focuses on mechanistic studies where proof-of-concept has been forwarded.