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  • The role of denervation in skeletal muscle of pre-frail/frail elderly women : [doctoral dissertation]
    Sonjak, Vita, 1989-
    "The aging process is associated with progressive decline in skeletal muscle mass and function contributing to impaired physical function and increased risk of frailty. Investigations on underlying ... mechanisms contributing to age-related muscle atrophy have revealed an important role of mitochondrial dysfunction and motor unit (MU) remodeling and loss. We have previously shown the presence of denervation and its modulating role on mitochondrial function in octogenarian men. However, limited data exists in elderly women, who are at a higher risk than men of becoming physically frail and who live longer with functional dependence. The aims of this Dissertation are to assess (i) mitochondrial function changes, and the potential modulating role of denervation on mitochondrial function in prefrail/frail elderly women, and (ii) the significance of denervation to muscle atrophy in pre-frail/frail elderly women. For comparison, we assessed the degree of muscle denervation in world class octogenarian master athletes (MA), who better retain muscle mass and physical function in advanced age. Here we showed that frail elderly women (FE, 77.9 % 1.5y) compared to young inactive (YI, 24.0 % 1.0) controls, have reduced vastus lateralis muscle respiratory capacity, which seemed to be due to reduced mitochondrial content rather than intrinsic dysfunction of mitochondria because the reduction in respiration was proportional to a reduction in the mitochondrial outer membrane protein, voltage dependent anion channel (VDAC). On the other hand, FE women displayed increased reactive oxygen species (ROS) per unit of VDAC that was normalized by blocking the denervation-responsive ROS signal through pharmacological inhibition of cytoplasmic phospholipase A2 (cPLA2). As such, our results suggest that denervation modulates mitochondrial function in FE similar to our previous observations in octogenarian men. Consistent with these findings, we also demonstrated the presence of denervation-induced morphological changes in the FE group compared to YI controls, including grouping of myofibers of the same type, changes in myofiber type (myosin heavy chain (MHC) protein isoform) characterized as increased abundance of fibers co-expressing multiple MHC isoforms, and an accumulation of small fibers that frequently have angular shape. Compared to YI group, FE women also displayed a higher abundance of neural cell adhesion molecule (NCAM) positive fibers and the presence of pyknotic nuclei, which are well-established marker of denervation. Next, we demonstrated that a population that maintains high physical function in advanced age, world class octogenarian track and field athletes (MA, 80.7 % 2.5y), compared to FE group, had lower abundance of fibers expressing NCAM and greater slow fiber type grouping with increased fiber number per group. This suggests that retention of muscle mass and function in high functioning elderly is associated with a greater capacity for reinnervating denervated muscle fibers such that over time, fewer fibers are lost. All together these data demonstrate that in FE women, denervation is an important modulator of mitochondrial function and contributes to age-related muscle atrophy and physical impairment as indicated by the presence of denervation-induced morphological changes and biomarkers in aging muscle. In contrast, highly functioning elderly adults exhibit features consistent with a greater reinnervation capacity, which likely plays a key role in their lesser degree of muscle degeneration and greater retention of physical function." --
    Vrsta gradiva - disertacija ; neleposlovje za odrasle
    Založništvo in izdelava - Montreal : [V. Sonjak], 2019
    Jezik - angleški
    COBISS.SI-ID - 17537588

Knjižnica/institucija Kraj Akronim Za izposojo Druga zaloga
Koroška osrednja knjižnica dr. Franca Sušnika Ravne na Koroškem Ravne na Koroškem SIKRA v čitalnico 1 izv.
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