Unknown fates of (brain) oxidation or UFO: Close encounters with neuronal senescence

Senescence as an Amyloid Cascade: The Amyloid Senescence Hypothesis

“…Although it is not always the case, when it comes to neurons it is common to see use of the term "senescent-like phenotype" (Walton and Andersen, 2019). Senescent-like is a conservative denomination that reflects potentially insurmountable challenges in the study of senescence in neurons.…”

“…For example, a widely used senescence marker in non-neuronal cells is senescence-associated-beta-galactosidase (SA-ß-Gal; Debacq-Chainiaux et al, 2009). However, SA-ß-Gal has been shown to be up-regulated in neurons that lack other senescence markers (Piechota et al, 2016;Musi et al, 2018;Walton and Andersen, 2019). SA-ß-Gal is lysosomal and reflects the increased lysosomal mass in senescent cells but is not necessary nor causes senescence (Kurz et al, 2000;Lee et al, 2006;Hernandez-Segura et al, 2018;Gorgoulis et al, 2019).…”

“…SA-ß-Gal is lysosomal and reflects the increased lysosomal mass in senescent cells but is not necessary nor causes senescence (Kurz et al, 2000;Lee et al, 2006;Hernandez-Segura et al, 2018;Gorgoulis et al, 2019). SA-ß-Gal in neurons has indeed been argued to simply reflect senescence-unrelated lysosome biogenesis (Piechota et al, 2016;Musi et al, 2018;Walton and Andersen, 2019). In order to prove neuronal senescence, multiple markers of senescence should be used which may include p16 INK4A , p21 CIP1 , Lamin B1, HMGB1, and amongst others (Hernandez-Segura et al, 2018;Gorgoulis et al, 2019).…”

“…Given that potential evidence for senescence in AD patients has existed for years, it is somewhat curious that research of senescence in neurobiology is only now blooming (Walton and Andersen, 2019). The historic paucity of studies of senescence in AD may be explained by a misunderstanding of mitotic cell biology.…”

“…As noted, senolytics have been demonstrated to have a therapeutic effect in a tau transgenic mice models (Bussian et al, 2018;Musi et al, 2018). Whether it is the killing of senescent neurons or senescent glia remains unclear (Walton and Andersen, 2019). In the case in which it was argued that senescent neurons were killed, it was speculated that senescence was caused by NFT mediated cell cycle entry (Musi et al, 2018).…”