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  • 1.
    Cristea, Alexander
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Qaisar, Rizwan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Karlsson Edlund, Patrick
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Bengtsson, Ewert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells2010In: Aging Cell, ISSN 1474-9718, E-ISSN 1474-9726, Vol. 9, no 5, p. 685-697Article in journal (Refereed)
    Abstract [en]

    The skeletal muscle fibre is a syncitium where each myonucleus regulates the gene products in a finite volume of the cytoplasm, i.e., the myonuclear domain (MND). We analysed aging- and gender-related effects on myonuclei organization and the MND size in single muscle fibres from six young (21–31 years) and nine old men (72–96 years), and from six young (24–32 years) and nine old women (65–96 years), using a novel image analysis algorithm applied to confocal images. Muscle fibres were classified according to myosin heavy chain (MyHC) isoform expression. Our image analysis algorithm was effective in determining the spatial organization of myonuclei and the distribution of individual MNDs along the single fibre segments. Significant linear relations were observed between MND size and fibre size, irrespective age, gender and MyHC isoform expression. The spatial organization of individual myonuclei, calculated as the distribution of nearest neighbour distances in 3D, and MND size were affected in old age, but changes were dependent on MyHC isoform expression. In type I muscle fibres, average NN-values were lower and showed an increased variability in old age, reflecting an aggregation of myonuclei in old age. Average MND size did not change in old age, but there was an increased MND size variability. In type IIa fibres, average NN-values and MND sizes were lower in old age, reflecting the smaller size of these muscle fibres in old age. It is suggested that these changes have a significant impact on protein synthesis and degradation during the aging process.

  • 2.
    Li, Meishan
    et al.
    Department of Physiology and Pharmacology AND Department of Clinical Neuroscience, Clinical Neurophysiology, Karolinska Institutet, Sweden.
    Ogilvie, Hannah
    Department of Physiology and Pharmacology AND Department of Clinical Neuroscience, Clinical Neurophysiology, Karolinska Institutet, Sweden.
    Ochala, Julien
    Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences and Medicine, King’s College London, UK.
    Artemenko, Konstantin A
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Iwamoto, Hiroyuki
    Japan Synchrotron Radiation Research Institute, Japan.
    Yagi, Naoto
    Japan Synchrotron Radiation Research Institute, Japan.
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Larsson, Lars
    Department of Physiology and Pharmacology AND Department of Clinical Neuroscience, Clinical Neurophysiology, Karolinska Institutet, Sweden.
    Aberrant post-translational modifications compromise human myosin motor function in old age2015In: Aging Cell, ISSN 1474-9718, E-ISSN 1474-9726, Vol. 14, no 2, p. 228-235Article in journal (Refereed)
    Abstract [en]

    Novel experimental methods, including a modified single fiber in vitro motility assay, X-ray diffraction experiments, and mass spectrometry analyses, have been performed to unravel the molecular events underlying the aging-related impairment in human skeletal muscle function at the motor protein level. The effects of old age on the function of specific myosin isoforms extracted from single human muscle fiber segments, demonstrated a significant slowing of motility speed (P < 0.001) in old age in both type I and IIa myosin heavy chain (MyHC) isoforms. The force-generating capacity of the type I and IIa MyHC isoforms was, on the other hand, not affected by old age. Similar effects were also observed when the myosin molecules extracted from muscle fibers were exposed to oxidative stress. X-ray diffraction experiments did not show any myofilament lattice spacing changes, but unraveled a more disordered filament organization in old age as shown by the greater widths of the 1, 0 equatorial reflections. Mass spectrometry (MS) analyses revealed eight age-specific myosin post-translational modifications (PTMs), in which two were located in the motor domain (carbonylation of Pro79 and Asn81) and six in the tail region (carbonylation of Asp900, Asp904, and Arg908; methylation of Glu1166; deamidation of Gln1164 and Asn1168). However, PTMs in the motor domain were only observed in the IIx MyHC isoform, suggesting PTMs in the rod region contributed to the observed disordering of myosin filaments and the slowing of motility speed. Hence, interventions that would specifically target these PTMs are warranted to reverse myosin dysfunction in old age.

  • 3.
    Maklakov, Alexei A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Animal Ecology.
    Fricke, Claudia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Animal Ecology.
    Arnqvist, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Animal Ecology.
    Sexual selection affects lifespan and aging in the seed beetle2007In: Aging Cell, ISSN 1474-9718, E-ISSN 1474-9726, Vol. 6, no 6, p. 739-744Article in journal (Refereed)
    Abstract [en]

    Sexual selection in general, and sexual conflict in particular, should affect the evolution of lifespan and aging. Using experimental evolution, we tested whether removal of sexual selection leads to the evolution of accelerated or decelerated senescence. We subjected replicated populations of the seed beetle Callosobruchus maculatus to either of two selection regimes for 35 generations. These regimes either allowed (polygamy) or removed the potential (monogamy) for sexual selection to operate. To test for the evolution of intrinsic differences between the two selection regimes, we assayed longevity in replicate cohorts of virgin females and males. Virgin females from populations evolving under sexual selection had reduced lifespan as predicted by the sexual conflict theory of aging. However, this reduction was due to increased baseline mortality rather than an increase in age-specific mortality rates with age. We discuss these findings in light of other data from this model system and suggest that system-specific idiosyncrasies may often modulate the general effects of male-female coevolution on the evolution of aging.

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