The "commentary on some recent theses" section is a regular feature of the Rejuvenation Research journal, penned by Aubrey de Grey and collaborators. Historically it has been behind a journal paywall, but it is presently open access - and in this day and age of organized copyright heretics who assemble online databases of papers normally locked away, it is ceasing to much matter whether or not journals maintain a paywall when it comes to access. The most recent commentary touches on a range of different topics; reading it all is recommended. The quoted material here relates to an interesting discovery regarding the senescence of astrocytes in the aging brain, which, as noted, offers the promise of effective near future treatments for a range of neurodegenerative conditions.
Of the seven strands of the SENS platform, the ablation of senescent cells (ApoptoSENS) has thus far made the most progress towards the clinic; drugs that selectively eliminate these toxic and superfluous cells are referred to as senolytics, and several are now undergoing or are soon to enter clinical trials. Recent evidence from preclinical work has indicated that the role of senescent cells in the aging process is remarkably significant, such that resolving this single form of damage yields dramatic benefits across the spectrum of age-related decline - simultaneously extending both lifespan and healthspan in mouse models.
Although the existence of a true senescent phenotype in postmitotic cells such as neurons is still unproven, its existence in their crucial support cells, the astrocytes, has been recognized since the beginning of this decade. A recent dissertation makes vital progress towards proving the clinical relevance of the phenomenon - laying the groundwork for the translational application of senolytics to major neurodegenerative diseases. Glutamate (together with aspartate) is the major excitatory neurotransmitter in the human brain, and dysfunctions of its handling are clearly associated with both acute and chronic neurological conditions. That such dysfunction is here shown to be an intrinsic consequence of physiologically realistic levels of astrocyte senescence leaves little doubt that a mechanistic connection must exist. In Alzheimer's disease specifically, it is notable that the loss of glutamate receptors in postmortem samples tracks both the brain's major excitatory pathways and also the very well-established progressive staging of the disease. These results are good news indeed!
Replacing intrinsically aged neurons without disrupting synaptic connectivity has always been accepted to be a daunting task, but astrocyte turnover - while low in healthy tissue - is a routine process following injury (albeit one that has side effects of its own when driven to excess in the context of chronic inflammation, although these appear somewhat treatable). Thus, depleting senescent astrocytes and so neutralizing their inflammatory effects may well automatically induce their replacement by healthy new cells; and even if not, stimulating that process is not an insurmountable challenge. At the very least, such a therapy should prevent further degeneration - and perhaps even create the conditions for the repair of pre-existing neuronal decline as well, especially since a subset of those astrocytes may be able to function as neural stem cells.