Darren Baker – Cell Senescence, Brain Aging, and Senotherapeutics for Neurodegenerative Disorders

Cells have evolved elaborate molecular systems that control cell growth and division in ways that enable optimal function and resilience of all organ systems including the brain. Cells that have the potential to become cancerous are eliminated by a process called apoptosis. Cells may also acquire a senescent state in which they no longer divide and function normally, but survive and produce potentially damaging proteins such as pro-inflammatory cytokines and proteases. Senescent cells accumulate during normal aging and more so in chronic diseases, but until recently it was not known whether such senescent cells cause or accelerate aging and disease processes . Mayo Clinic Professor Darren Baker who is an expert on the molecular control of cell division and cancers recently used genetic engineering technologies to generate mice in which senescent cells can be selectively eliminated. By studying these mice he and his team have provided convincing evidence that senescent cells contribute to the aging process and are involved in the disease processes that occur in Alzheimer's disease (AD). There is evidence that several types of glial cells in the brain undergo senescence and removal of these cells can slow disease progression. I talk with Dr. Baker about his research on cell senescence, key issues that remain unresolved, and drugs that target senescent cells – "senotherapeutics" as potential treatments for AD and other neurodegenerative disorders.

Dr. Baker's Mayo Clinic Profile page:

https://www.mayo.edu/research/faculty/baker-darren-j-ph-d-m-s/bio-00027985

Review article on senescence and brain aging: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873891/pdf/jci-128-95145.pdf

Introduction to special journal issue on senescence: https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.16735

Review article on senotherapeutics: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599677/pdf/nihms-1842277.pdf

Targeted removal of senescent cells and senotherapeutics in animal models of AD:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206507/pdf/nihms-1505435.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939718/pdf/nihms-1968907.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605052/pdf/nihms-1031989.pdf