Studying the structure and function of the ageing platelet
Platelets are key regulators of haemostasis and exist within the circulation of a healthy individual for approximately 10 days. Formed as anuclear fragments of parent megakaryocytes they cannot synthesise new proteins. It has been thought that in general terms younger platelets are more reactive than older platelets and their increased levels have been clinically correlated with adverse cardiovascular outcomes. However, to date no conclusive studies have been conducted to characterise the differences that exist between ‘young’ and ‘old’ platelets, nor detail the changes that occur as they age in the circulation.
Using novel approaches in tracking and isolating ‘young’ and ‘old’ platelets in mice and human blood it is now possible to functionally assess and molecularly phenotype platelets at different stages of their lifespan.
Our data so far indicates that young platelets contain the greatest levels of mRNA and contribute disproportionately to drive forming thrombi. This enhanced platelet reactivity is in part due to a differential receptor profile, higher calcium dynamics, granule secretion and eicosanoid production. In line with these observations proteomic analysis has identified higher levels of hemostasis associated proteins in young platelets, whilst apoptosis and senescence associated proteins are higher in old platelets. Most notably platelet ageing is associated with a reduction in mitochondrial and structural proteins. However contrary to common belief, new platelets are heterogenous in size, with a similar size distribution to older populations, and that their size does not change as they age.
This ongoing research is providing new insights into critical mechanisms underlying the control of platelet life span. Such information will inform our understanding of how newly formed platelets vary in health and disease, how platelets age differently under physiological and pathological circumstances, and how drug interventions could be used to regulate platelet lifespan and so influence disease progression.
The seminar will be hosted using Zoom. A Google calendar invite featuring the Zoom link will be sent to Biology staff and students before the seminar date. For all enquiries please contact Biology DMT Hub.
(Rescheduled from October 2020.)