## 5 Conclusions and Perspectives  
In conclusion, the present and previous studies demonstrate that alterations in levels of cathepsin activity may not correspond to drastic changes in tissue morphology and/or protein homeostasis [1; 18; 58]. However, the results highlight once more the importance of examining both protease protein amounts and their activity levels in biological systems to better understand and predict the effectiveness of inhibitor therapeutics. Overall, this study has identified variations in the cathepsin proteolytic network in the CNS of aging mice, and the findings provide insights into regional differences of the somewhat redundant cysteine cathepsin protease network. An understanding of the various aspects of cathepsin dynamics will lead to more effective application in inhibitor therapy for diseases with higher incidences in aging populations.  
Conceptualization, D.M.T.Y., S.D., S.J. and K.B.; Data curation, D.M.T.Y., S.D., S.J. and K.B.; Formal analysis, D.M.T.Y., S.D., S.J. and K.B.; Funding acquisition, D.M.T.Y., S.D. and K.B.; Investigation, D.M.T.Y., S.D., M.B.M., V.S., M.R. and S.J.; Methodology, D.M.T.Y., S.D., M.B.M., V.S., M.R. and S.J.; Project administration, D.M.T.Y., S.D. and K.B.; Resources, K.B.; Supervision, D.M.T.Y. and K.B.; Validation, D.M.T.Y. and S.D.; Visualization, D.M.T.Y., S.D., M.B.M., V.S., M.R. and S.J.; Writing--original draft, D.M.T.Y., S.D. and K.B.; Writing--review and editing, D.M.T.Y., S.D., M.B.M., V.S., M.R., S.J. and K.B. All authors have read and agreed to the published version of the manuscript.  
**Funding:** This research was funded by a grant from the Deutscher Akademischer Austausch Dienst (DAAD), DAAD-A9/09/97458, to D.M.T.Y. and by Jacobs University Bremen, who provided a stipend to S.D., and Projects 2140/90140 and 6113/90140 to K.B., as well as the Research Centers AgeAct and MOLIFE at Jacobs University Bremen to D.M.T.Y., K.B., S.D. and K.B.  
**Institutional Review Board Statement:** Animal studies were carried out in compliance with the institutional guidelines in S1 laboratories of Jacobs University Bremen (Senatorin fur Gesundheit, Frauen und Verbraucherschutz der Hansestadt Bremen, Bremen, Germany, Az. 513-30-00/2-15-32 including K.B. as project leader, and Az. 0515_2040_15 to K.B. authorizing animal breeding, housing, and sacrifice of genetically engineered mice.  
**Informed Consent Statement:** This article does not contain any studies with human participants performed by any of the authors.  
**Data Availability Statement:** All data are included in the manuscript. Note that the data of this manuscript are partially included in chapter 4.6 of the dissertation of S.D. that is publicly available at [[http://nbn-resolving.org/urn:nbn:de:101:1-201305294530](http://nbn-resolving.org/urn:nbn:de:101:1-201305294530)]([http://nbn-resolving.org/urn:nbn:de:101:1-201305294530](http://nbn-resolving.org/urn:nbn:de:101:1-201305294530)) (accessed on 12 January 2022).  
**Acknowledgments:** The authors are grateful to [PERSON] (Jacobs University Bremen) for his excellent assistance in animal keeping. We are grateful to [PERSON] (Jacobs University Bremen) for helpful comments. The authors are grateful to [PERSON]. Institute of Biochemistry, Christian-Albrechts-University Kiel, Germany, for providing the cathepsin-K-deficient mouse model, and to [PERSON] and [PERSON], Institute for Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Germany, for providing the cathepsin-B- and L-deficient mouse models.  
**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.