We appreciate Iyer and Dayal's insightful comments, and interest in our recent study [1]. They raise thoughtful and important points about the documented higher thrombotic risk in the very old age. However, the increase in platelet reactivity with age in our 60–79 age cohort, and its relative decline in the 80 and above aged elderly cohort, does not contradict the known increase in risk of thrombosis with age [2]. Hemostasis, is a complex interplay between platelet reactivity, tissue injury/damage, and coagulation/fibrinolysis. Higher levels of FVIIIa, FIXa and fibrinogen have been documented in the elderly [3, 4]. Moreover, centenarians have been shown to have higher levels of factor X activation peptide, prothrombin fragment 1+ 2, thrombin/antithrombin complex and fibrinopeptide A, all of which promote thrombosis, with no increase in the anticoagulant proteins such as Protein C, S, TFPI [5]. Thus, decreased platelet reactivity in advanced age (both human and mice)[1] is likely a beneficial adaptive response, important in counterbalancing the hypercoagulation state (due to the increased procoagulant proteins) in the elderly. Further follow up studies are needed to dissect the relative contributions of platelets and other hemostasis components in the elderly.

As far as we are aware, our study is the first longitudinal mouse study with regular blood sampling and analysis of platelet redox biology from an early age to death. As suggested by Iyer and Dayal, the changes in platelet antioxidants with age are likely adaptive. Our data from the platelets of a randomly selected group of mice, followed over a period of 12 months, supports an interplay of both adaptive as well as selective mechanisms, which may also play a role in survival. Consistent with the cross-sectional mice (and human) results, we observed that platelets from individual mice showed a progressive drop in antioxidants as they aged to 12 months. However, as their age advanced over 14 months of age, there was a notable increase in catalase and SOD activity, along with a concomitant decline in ROS and sP-selectin levels (a likely mechanism to counter the increasing oxidative stress). However, consistent with the earlier reports [6], our results also show that ROS and sP-selectin levels are elevated in 18 month mice as compared to the 6-month old mice, when considered at the single respective time points. As suggested by Iyer and Dayal, there could very well be