Possible trade-offs between robustness in metabolism and frailty in infection in CR. Trade-offs between robustness and frailty are an inherent, unavoidable feature of complex systems, such as biological systems. Whereas CR promotes metabolic robustness, it appears to increase frailty to infections pathogens. Given that sirtuin (SIRT1 in particular) activating compounds (STACs) function as a potential CR mimetics, STACs might also convey similar trade-offs. Therefore, it will be critical to seek an optimal balance between robustness in metabolism and frailty in infection in our complex physiological system.