Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells

Abstract

SummaryThe 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.

Sarcopenia, Dynapenia, and the Impact of Advancing Age on Human Skeletal Muscle Size and Strength; a Quantitative Review

“…There is further evidence supporting a selective decrease in size of type II fibers (Larsson, 1978; Coggan et al, 1992; Larsson et al, 1997; Cristea et al, 2010) though some also suggest a decrease in diameter of type I fibers (D’Antona et al, 2003). Another histological study suggested that whilst type II fiber size reduce by c. 57%, type I fibers shrunk by 25% between the third and ninth decades (Andersen, 2003).…”

“…Nuclei are fixed in a non-random distribution throughout within each fiber, each nucleus regulating protein synthesis within a volume of cytoplasm, its myonuclear domain (MND). Muscle fibers may contain many thousand nuclei; for example in human vastus lateralis each fiber contains about 100 nuclei per millimeter length (Cristea et al, 2010). Arranged along the surface of each muscle fiber are satellite cells which function as a stem cell population; satellite cell mitosis can replenish myonuclear number and producing new satellite cells throughout life.…”

“…However the most recent developments in assessing the spatial arrangement of myonuclei have demonstrated little or no change in average MND size with aging. Instead there is an apparent increase in the variability of size of MND and a clustering of myonuclei within grooves on the periphery of the fiber which may itself have implications in the efficiency of the myonuclear control of muscle protein synthesis (MPS; Cristea et al, 2010). …”

Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

“…2A), which reduce functional capacity together with extrinsic factors (Brooks and Faulkner, 1994; Nair, 2005). Muscles of aged mammals show fiber atrophy (Fujisawa, 1974; Fujisawa, 1975; Tomonaga, 1977), increased apoptosis (Marzetti and Leeuwenburgh, 2006), DNA damage (Aiken et al, 2002; Szczesny et al, 2010), reduced protein synthesis (Hasten et al, 2000; Yarasheski et al, 1999), age-related decline in autophagic degradation (Wohlgemuth et al, 2010), lysosomal dysfunction (accumulation of lipofuscin deposits) (Beregi et al, 1988; Hütter et al, 2007), accumulation of advanced glycation end-products (Snow et al, 2007), insoluble polyubiquitylated proteins (Yamaguchi et al, 2007), increased heterochromatin marks (Kreiling et al, 2011), changes in microRNA expression (Drummond et al, 2011), and altered nuclear shape and spatial disorganization of nuclei (Cristea et al, 2010). …”

“…In particular, aging is characterized in mice and Drosophila by an increase in the number of muscle nuclei having aberrant shape, condensed chromatin and spatial disorganization (Brandt et al, 2008; Cristea et al, 2010). The nuclear lamina, which maintains the shape and mechanical stability of the nucleus, and nuclear pore complexes (NPCs), which mediate the transport of molecules across the nuclear envelope, are thought to be particularly sensitive to age-related damage.…”