Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300: response to correspondence by Borzì et al.

We welcome the comments and research efforts by Borzì et al. mirroring our work highlighting the significance of longevity-related mechanisms in skeletal biology (sirtuins, autophagy(definition)) and how naturally occurring non-specific products (polyamines, polyphenols) might prolong cell mortality. Specifically, Borzì et al. appear to agree with our recent conclusion that spermidine activates autophagy and is chondroprotective, yet the intricate dynamics of epigenetic and/or post-translational modifications at play within this system have served to obfuscate this message. Borzì et al. correctly indicate that our referenced literature describes known interactions between the EP300 acetyltransferase and a selection of the 170 proteins forming the human autophagy protein network. We intentionally highlight the varied and contradictory effects of protein acetylation upon normal cellular processes, suggesting that fine tuning of autophagy occurs through changes in epigenetic modifiers, and which might alter with disease state or environmental stimuli.