Browsing by Subject "Aging / physiology"

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Aging-related limit of exercise efficacy on motor decline
(PLOS, 2017-11-27) Arnold, Jennifer C.; Cantu, Mark A.; Kasanga, Ella A.; Nejtek, Vicki A.; Papa, Evan V.; Bugnariu, Nicoleta; Salvatore, Michael F.
Identifying lifestyle strategies and allied neurobiological mechanisms that reduce aging-related motor impairment is imperative, given the accelerating number of retirees and increased life expectancy. A physically active lifestyle prior to old age can reduce risk of debilitating motor decline. However, if exercise is initiated after motor decline has begun in the lifespan, it is unknown if aging itself may impose a limit on exercise efficacy to decelerate further aging-related motor decline. In Brown-Norway/Fischer 344 F1 hybrid (BNF) rats, locomotor activity begins to decrease in middle age (12-18 months). One mechanism of aging-related motor decline may be decreased expression of GDNF family receptor, GFRalpha-1, which is decreased in substantia nigra (SN) between 12 and 30 months old. Moderate exercise, beginning at 18 months old, increases nigral GFRalpha-1 and tyrosine hydroxylase (TH) expression within 2 months. In aged rats, replenishing aging-related loss of GFRalpha-1 in SN increases TH in SN alone and locomotor activity. A moderate exercise regimen was initiated in sedentary male BNF rats in a longitudinal study to evaluate if exercise could attenuate aging-related motor decline when initiated at two different ages in the latter half of the lifespan (18 or 24 months old). Motor decline was reversed in the 18-, but not 24-month-old, cohort. However, exercise efficacy in the 18-month-old group was reduced as the rats reached 27 months old. GFRalpha-1 expression was not increased in either cohort. These studies suggest exercise can decelerate motor decline when begun in the latter half of the lifespan, but its efficacy may be limited by age of initiation. Decreased plasticity of GFRalpha-1 expression following exercise may limit its efficacy to reverse motor decline.
Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis
(Springer Nature, 2019-02-27) Das, Pragnya; Panda, Santosh K.; Agarwal, Beamon; Behera, Sumita; Ali, Syed M.; Pulse, Mark E.; Solomkin, Joseph S.; Opal, Steven M.; Bhandari, Vineet; Acharya, Suchismita
In Gram-negative bacterial sepsis, production of excess pro-inflammatory cytokines results in hyperinflammation and tissue injury. Anti-inflammatory cytokines such as IL-10 inhibit inflammation and enhance tissue healing. Here, we report a novel approach to treat septicemia associated with intra-abdominal infection in a murine model by delicately balancing pro- and anti-inflammatory cytokines. A novel oligosaccharide compound AVR-25 selectively binds to the TLR4 protein (IC50 = 0.15 µM) in human peripheral blood monocytes and stimulates IL-10 production. Following the cecal ligation and puncture (CLP) procedure, intravenous dosing of AVR-25 (10 mg/kg, 6-12 h post-CLP) alone and in combination with antibiotic imipenem protected both young adult (10-12 week old) and aged (16-18 month old) mice against polymicrobial infection, organ dysfunction, and death. Proinflammatory cytokines (TNF-ɑ, MIP-1, i-NOS) were decreased significantly and restoration of tissue damage was observed in all organs. A decrease in serum C-reactive protein (CRP) and bacterial colony forming unit (CFU) confirmed improved bacterial clearance. Together, these findings demonstrate the therapeutic ability of AVR-25 to mitigate the storm of inflammation and minimize tissue injury with high potential for adjunctive therapy in intra-abdominal sepsis.