TITLE:
Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease
AUTHORS:
Joaquín Lasierra-Cirujeda, María José Aza Pascual-Salcedo, Alicia Lasierra-Ibañez, Carmen Lasala Aza, María Mercedes Aza Pascual-Salcedo
KEYWORDS:
Aging, Alzheimer’s Disease, T2DM, PAI-1, Glutathione
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.4 No.5,
May
10,
2016
ABSTRACT: Aging can be interpreted as an unavoidable
process whose end point is the death. Aging entails, in the hemostasis field,
some changes that favour blood hypercoagulability. Both the plasminogen
activator inhibitor (PAI-1), specific inhibitor of the tissue plasminogen
activator (t-PA), accompanied by the oxidative
stress and the marked decrease of the main antioxidant—glutathione are
fundamental in the bases of elderly pathologies which can cause death. There is
some scientific evidence of the relationship between aging, neuro-degenerative
diseases, an excessive production of reactive oxygen species and the decrease
of proteolysis in brain. The cerebral plasminogen/plasmin system represents
the essential proteolytic mechanism that degrades amyloid peptides (β-amyloidosis) for action of plasmin
with effectiveness. This physiologic process is being considered as a
preventive neurodegenerative mechanism. At the same time, the decrease of
glutathione levels in aging entails a decrease of cerebral plasmin activity and
a progressive descent of t-PA activity due to a descent in t-PA expression and
an increase in PAI production. All of them entail an increment of amyloid beta
peptides (Aβ) production and a lower
level of their clearance. Both mechanisms, oxidative stress, direct consequence
of the oxygenate metabolism of aerobics cells, and changes in the systemic
fibrinolysis and cerebral b-amyloidolytic activity, play a very important role
in thromboembolic disease, metabolic syndrome—obesity, insulin resistance, hyperglycemia—,
type 2 Diabetes Mellitus and Alzheimer’s disease, clinical processes that
accompany the aging. In this revision we show the importance of the interaction
between glutathione, proteolytic t-PA/plasminogen/plasmin system, and the
inhibitor PAI-1 in aging physiopathology, whose results suggest the hypothesis
of the importance of a therapeutic strategy using the inhibition of PAI-1 as a goal, because it is increased in the
different aging pathologic processes.