Abstract:
:Angiogenesis - the growth of new blood capillaries- is impaired in aging animals. Biophysical factors such as changes in cell size control endothelial cell (EC) proliferation and differentiation. However, the effects of aging on EC size and the mechanism by which changes in cell size control age-dependent decline in EC proliferation are largely unknown. Here, we have demonstrated that aged ECs are larger than young ECs and that age-dependent increases in EC size control EC proliferation and senescence through CDC42-Yes-associated protein (YAP1) signaling. Reduction of aged EC size by culturing on single-cell sized fibronectin-coated smaller islands decreases CDC42 activity, stimulates YAP1 nuclear translocation and attenuates EC senescence. Stimulation of YAP1 or inhibition of CDC42 activity in aged ECs also restores blood vessel formation. Age-dependent changes in EC size and/or CDC42 and YAP1 activity may be the key control point of age-related decline in angiogenesis.
journal_name
Aging (Albany NY)journal_title
Agingauthors
Mammoto T,Torisawa YS,Muyleart M,Hendee K,Anugwom C,Gutterman D,Mammoto Adoi
10.18632/aging.102236subject
Has Abstractpub_date
2019-09-05 00:00:00pages
7051-7069issue
17issn
1945-4589pii
102236journal_volume
11pub_type
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