Altered functions of platelets during aging

Abstract

Purpose of review: Platelets are specialized effector cells that rapidly respond to sites of vascular injury. However, emerging data demonstrate that platelets possess diverse functions that also mediate inflammatory responses and neurological diseases. These functions are relevant to disease processes prevalent among older adults and likely influence susceptibility to thrombotic and inflammatory disorders.

Recent findings: Platelet counts decrease in aged individuals whereas platelet reactivity increases. The platelet transcriptome is altered in aged individuals resulting in altered platelet function and exaggerated inflammation. Platelet signaling to monocytes in aging results in significantly more cytokines because of increased platelet-derived granzyme A. Platelet activation in aging appears to be driven, in part, because of increased reactive oxygen species and activation of the mammalian target of rapamycin pathway. Increased platelet hyperactivity in diseases is associated with aging, such cardiovascular disease and sepsis, exaggerate inflammation and thrombosis. Noncanonical functions of platelets influence the development of neurological diseases including Alzheimer's disease.

Summary: Although there have been advances dissecting the molecular mechanisms regarding aging-related changes in platelets, many knowledge gaps still remain. Studies filling these gaps are likely to identify new mechanisms driving aging-related changes in platelet gene expression and function, and contributing to injurious thrombo-inflammation in older adults.

Conflict of interest statement

Conflict of Interest.

None

Figures

Figure 1.. Altered platelet functions during aging.

Aging is associated increased reactive oxygen species (ROS) generation in platelets due to mitochondrial dysfunction. ROS activates the mTOR signaling pathway resulting in increased platelet activation. In older individuals, platelet activation is characterized by increased αIIβ3 integrin activation. Degranulation upon activation induces the releases of coagulation factors and inflammatory mediators. Increased P-selectin expression and release of granzyme A from platelets promotes the formation of platelet-monocyte aggregations and secretion of pro-inflammatory cytokines. These cytokines and platelet-derived cytokines released from granules and PMP promote endothelial activation and increased systemic inflammation. Together, these events contribute to increased systemic inflammation and elevated risk for atherothrombotic events in aging.