Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice.
Odette LeiterDavid BriciStephen J FletcherXuan Ling Hilary YongJocelyn WidagdoNicholas MatigianAdam B SchroerGregor BieriDaniel G BlackmorePerry F BartlettVictor AnggonoSaul A VilledaTara L WalkerPublished in: Nature communications (2023)
The beneficial effects of physical activity on brain ageing are well recognised, with exerkines, factors that are secreted into the circulation in response to exercise, emerging as likely mediators of this response. However, the source and identity of these exerkines remain unclear. Here we provide evidence that an anti-geronic exerkine is secreted by platelets. We show that platelets are activated by exercise and are required for the exercise-induced increase in hippocampal precursor cell proliferation in aged mice. We also demonstrate that increasing the systemic levels of the platelet-derived exerkine CXCL4/platelet factor 4 (PF4) ameliorates age-related regenerative and cognitive impairments in a hippocampal neurogenesis-dependent manner. Together these findings highlight the role of platelets in mediating the rejuvenating effects of exercise during physiological brain ageing.
Keyphrases
- cerebral ischemia
- physical activity
- high intensity
- subarachnoid hemorrhage
- cell proliferation
- blood brain barrier
- brain injury
- white matter
- resting state
- high fat diet induced
- mesenchymal stem cells
- body mass index
- multiple sclerosis
- functional connectivity
- red blood cell
- cell therapy
- depressive symptoms
- adipose tissue
- pi k akt