Editorial Volume 13, Issue 5 pp 6233—6235

Flux control in the aging cascade

Flux control in radical chain reactions in relation to biological aging. Radical chain reactions have three kinetically independent steps: initiation, propagation and termination. The prevention of initiation is the designated task of antioxidant enzymes like SOD. Accelerating termination is the designated task of chain-breaking antioxidants like vitamin E. Propagation, though, has never been shown to be specifically influenced by any biomolecule [3]. It is only modulated by the availability of substrate (S) and the presence (or absence) of chain-transfer catalysts, which increase the propagation constant [3,8]. The two most robust evolutionary adaptations of long-lived animals, lowered polyunsaturated fatty acids [4], and fewer intramembrane cysteine residues [7], both slow down propagation, but have no direct connection to initiation or termination [3,8]. Damage repair is depicted for comparison, as one of several different defense strategies against aging. Very likely, damage repair also exerts flux control over aging (consider rapamycin), but the kinetically limiting steps are essentially unknown (e.g., recognition vs. excision vs. replacement). Abbreviations: I•, initiator radical; S•, substrate radical; P, product; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; E, tocopherol; Q10, ubiquinone.

Figure 1. Flux control in radical chain reactions in relation to biological aging. Radical chain reactions have three kinetically independent steps: initiation, propagation and termination. The prevention of initiation is the designated task of antioxidant enzymes like SOD. Accelerating termination is the designated task of chain-breaking antioxidants like vitamin E. Propagation, though, has never been shown to be specifically influenced by any biomolecule [3]. It is only modulated by the availability of substrate (S) and the presence (or absence) of chain-transfer catalysts, which increase the propagation constant [3,8]. The two most robust evolutionary adaptations of long-lived animals, lowered polyunsaturated fatty acids [4], and fewer intramembrane cysteine residues [7], both slow down propagation, but have no direct connection to initiation or termination [3,8]. Damage repair is depicted for comparison, as one of several different defense strategies against aging. Very likely, damage repair also exerts flux control over aging (consider rapamycin), but the kinetically limiting steps are essentially unknown (e.g., recognition vs. excision vs. replacement). Abbreviations: I•, initiator radical; S•, substrate radical; P, product; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; E, tocopherol; Q10, ubiquinone.