Brain: Some proteins are surprisingly long lived & resist proteasome decay, leading in pathological cases to prion disorders such as Creutzfeldt-Jakob disease; how this works at molecular levels & relates to age-related cellular burden in neurons that never “rejuvenate” through cell division?

Chapter 3. Prahlad & Chikka: Aging and the brain. In The Wiley Handbook on the Aging Mind and Brain. https://doi.org/10.1002/9781118772034.ch3

This chapter reviews molecular and cellular aspects of aging in the context of the evolution of aging. What is the advantage to humankind of long living? Organismal aging as a postreproductive process is not under strong reproductive selection. Extensions of lifespan may even correlate with reduced reproduction. The oldest known person ever, Jeanne Calment, died at age 122 and had only one daughter. Hers is a prominent human example of a broader inverse relationship between longevity and fertility across species, whose foundations remain unclear. A central theme of aging is the molecular and cellular instability and the role of the brain in regulating these processes. Some proteins are surprisingly long lived and resist proteasome decay, leading in pathological cases to prion disorders such as Creutzfeldt-Jakob disease. The authors review how this works at molecular levels and relates to age-related cellular burden in neurons that never “rejuvenate” through cell division. Parabiosis, or sharing of blood circulation of two organisms of different age, is the best known example of how blood-born molecules can affect organism vitality and longevity, possibly through additional trophic factors in the brain. This chapter lays biological foundations for interpreting findings on the aging mind and brain covered throughout this book.