An open access review paper here looks at some of the low-level processes involved in late-life neurodegeneration, the decline of brain functionality. If following a SENS-like viewpoint of the causes of degenerative aging, we would say that these are secondary processes, a loss in the ability of brain tissue and brain cells to maintain themselves due to forms of accumulated damage that occur at an even lower functional level in our biology.
The core point of the SENS proposals for rejuvenation biotechnology is that we don't need to understand the very complex middle layers of degeneration and maintenance in order to halt and reverse aging - we just need to fix the lowest-level causes of aging, which are presently well known. All have associated strategies that will lead to repair or reversal of their effects. Still, most of the research community continues to focus instead on generating a complete understanding of the exceedingly complex processes of aging, starting from the mid-layers and working out:
Most neurons are born with the potential to live for the entire lifespan of the organism. In addition, neurons are highly polarized cells with often long axons, extensively branched dendritic trees and many synaptic contacts. Longevity together with morphological complexity results in a formidable challenge to maintain synapses healthy and functional.
This challenge is often evoked to explain adult-onset degeneration in numerous neurodegenerative disorders that result from otherwise divergent causes. However, comparably little is known about the basic cell biological mechanisms that keep normal synapses alive and functional in the first place. How the basic maintenance mechanisms are related to slow adult-onset degeneration in different diseases is largely unclear.
In this review we focus on two basic and interconnected cell biological mechanisms that are required for synaptic maintenance: endomembrane recycling and calcium (Ca2+) homeostasis. We propose that subtle defects in these homeostatic processes can lead to late onset synaptic degeneration. Moreover, the same basic mechanisms are hijacked, impaired or overstimulated in numerous neurodegenerative disorders. Understanding the pathogenesis of these disorders requires an understanding of both the initial cause of the disease and the on-going changes in basic maintenance mechanisms. Here we discuss the mechanisms that keep synapses functional over long periods of time with the emphasis on their role in slow adult-onset neurodegeneration.