Taken together, the data presented here suggest that intervention with AAV-Kl may be more effective in slowing the progression of sarcopenia at an earlier timepoint, rather than rescuing advanced pathology, at which time the transcriptomic response to intervention appears to be more stochastic. An interesting area of future investigation includes the determination of whether network entropy and PPI network architecture may be predictive of the efficacy of therapies designed to counteract the effect of time on skeletal muscle health and function. As an extension of this work, it would also be interesting in future studies to determine whether upregulation of Klotho at a younger age could attenuate functional declines into old, and possibly even oldest-old, age
^ALSO TRUE FOR SENOLYTICS - THEY WORK BETTER IN YOUNGER PEOPLE (BOTH THE BLUNT-FORCE D+Q AND THE OSIRIN BIOTECH TYPE). Also POSSIBLY for follistatin gene therapy
slowing aging is MUCH easier than reversal, and the earlier, the better (when aging increases the entropy of the cell, the “repair/age-reversal signals” don’t know where to be precisely targeted anymore).
endolysosomal system has been well studied in non-neuronal cells and broadly classified into several subclasses, including the EE (early endosome), RE (recycling endosome), LE (late endosome), and lys (lysosome). The EE is the major sorting station for endocytosed receptors. Recycling cargos can return to the surface from the EE or from the RE. Degradative cargos fail to enter recycling pathways in the EE and are progressively sorted into intraluminal vesicles starting in the EE. The EE matures to a LE by the timed exchange of specific effectors, proteins that associate with the cytosolic leaflet of the endosome membrane, such as Rab7. LEs contain many intraluminal vesicles and are often categorized by EM as “multivesicular bodies.” LEs undergo homotypic fusions with each other as well as fuse with lysosomes for cargo degradation; and in some cases, they fuse with the plasma membrane