scholarly journals Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction

2013 ◽  
Vol 304 (8) ◽  
pp. C717-C728 ◽  
Author(s):  
Bryon R. McKay ◽  
Daniel I. Ogborn ◽  
Jeff M. Baker ◽  
Kyle G. Toth ◽  
Mark A. Tarnopolsky ◽  
...  
Keyword(s):  
Stem Cell ◽  
Young Male ◽  
The Elderly ◽  
Knee Extension ◽  
Cytokine Signaling ◽  
Muscle Stem Cell ◽  
Adult Men ◽  
Cell Dysfunction ◽  
Age Related ◽  
Socs3 Protein

Aging is associated with increased circulating interleukin-6 (IL-6) and a reduced myogenic capacity, marked by reduced muscle stem cell [satellite cell (SC)] activity. Although IL-6 is important for normal SC function, it is unclear whether elevated IL-6 associated with aging alters SC function. We hypothesized that mild chronically elevated IL-6 would be associated with a blunted SC response through altered IL-6 signaling and elevated suppressor of cytokine signaling-3 (SOCS3) in the elderly. Nine healthy older adult men (OA; 69.6 ± 3.9 yr) and 9 young male controls (YC; 21. 3 ± 3.1 yr) completed 4 sets of 10 repetitions of unilateral leg press and knee extension (75% of 1-RM). Muscle biopsies and blood were obtained before and 3, 24, and 48 h after exercise. Basal SC number was 33% lower in OA vs. YC, and the response was blunted in OA. IL-6+/Pax7+ cells demonstrated a divergent response in OA, with YC increasing to 69% at 3 h and peaking at 24 h (72%), while IL-6+/Pax7+ cells were not increased until 48 h in OA (61%). Type II fiber-associated phosphorylated signal transducer and activator of transcription (pSTAT3)+/Pax7+ cells demonstrated a similar delay in OA, not increasing until 48 h (vs. 3 h in YC). SOCS3 protein was 86% higher in OA. These data demonstrate an age-related impairment in normal SC function that appears to be influenced by SOCS3 protein and delayed induction of IL-6 and pSTAT3 in the SCs of OA. Collectively, these data suggest dysregulated IL-6 signaling as a consequence of aging contributes to the blunted muscle stem cell response.

Myostatin is associated with age‐related human muscle stem cell dysfunction

2012 ◽  
Vol 26 (6) ◽  
pp. 2509-2521 ◽  
Author(s):  
Bryon R. McKay ◽  
Daniel I. Ogborn ◽  
Leeann M. Bellamy ◽  
Mark A. Tarnopolsky ◽  
Gianni Parise
Keyword(s):  
Stem Cell ◽  
Human Muscle ◽  
Muscle Stem Cell ◽  
Cell Dysfunction ◽  
Age Related

Neuroendocrine rhythms and sleep in aging men

1991 ◽  
Vol 260 (4) ◽  
pp. E651-E661 ◽  
Author(s):  
A. van Coevorden ◽  
J. Mockel ◽  
E. Laurent ◽  
M. Kerkhofs ◽  
M. L'Hermite-Baleriaux ◽  
...  
Keyword(s):  
Young Male ◽  
Extended Period ◽  
The Elderly ◽  
Thyroid Stimulating Hormone ◽  
Temporal Organization ◽  
Elderly Subjects ◽  
Elderly Men ◽  
Age Related ◽  
Aging Men ◽  
Effects Of Aging

To delineate the physiological effects of aging on basal levels and temporal patterns of neuroendocrine secretions, the 24-h profiles of cortisol, thyroid-stimulating hormone (TSH), melatonin, prolactin, and growth hormone (GH) levels were simultaneously obtained at frequent intervals in eight healthy, active elderly men, age 67-84 yr and in eight young male adults, age 20-27 yr. The study was preceded by an extended period of habituation to laboratory conditions, and sleep was polygraphically recorded. Mean cortisol levels in the elderly were normal, but the amplitude of the circadian rhythm was reduced. Circulating levels of daytime and nighttime levels of both TSH and GH were greatly diminished in old age. In contrast, prolactin and melatonin concentrations were decreased during the nighttime only. The circadian rises of cortisol, TSH, and melatonin occurred 1-1.5 h earlier in elderly subjects, and the distribution of rapid-eye-movement stages during sleep was similarly advanced, suggesting that circadian timekeeping is modified during normal senescence. Despite perturbations of sleep, sleep-related release of GH and prolactin occurred in all elderly men. Age-related decreases in hormonal levels were associated with a decrease in the amplitude, but not the frequency, of secretory pulses. These findings demonstrate that the normal process of aging involves alterations in the central mechanisms controlling the temporal organization of endocrine release in addition to a reduction of secretory outputs.

Reversal of Aged Muscle Stem Cell Dysfunction

2016 ◽  
Vol 19 (5) ◽  
pp. 423-429 ◽  
Author(s):  
James W. Larrick ◽  
Jasmine W. Larrick ◽  
Andrew R. Mendelsohn
Keyword(s):  
Stem Cell ◽  
Muscle Stem Cell ◽  
Cell Dysfunction

scholarly journals Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging

2015 ◽  
Vol 7 (2) ◽  
pp. 73
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Satellite Cell ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Cell Function ◽  
Muscle Stem Cell ◽  
Muscle Aging ◽  
Age Related

BACKGROUND: Age-related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility and an increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle regeneration is a complex process, which is not yet completely understood.CONTENT: Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Recent studies have delineated that the aging process in organ stem cells is largely caused by age-specific changes in the differentiated niches, and that regenerative outcomes often depend on the age of the niche, rather than on stem cell age. It is likely that epigenetic states will be better define such key satellite cell features as prolonged quiescence and lineage fidelity. It is also likely that DNA and histone modifications will underlie many of the changes in aged satellite cells that account for age-related declines in functionality and rejuvenation through exposure to the systemic environment.SUMMARY: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Decreased muscle stem cell function in aging has long been shown to depend on altered environmental cues, whereas the contribution of intrinsic mechanisms remained less clear. Signals in the aged niche were shown to cause permanent defects in the ability of satellite cells to return to quiescence, ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: satellite cell, muscle, aging, niche, regenerations

scholarly journals Perspectives of Stem Cell–Based Therapy for Age-Related Retinal Degenerative Diseases

2017 ◽  
Vol 26 (9) ◽  
pp. 1538-1541 ◽  
Author(s):  
Vladimir Holan ◽  
Barbora Hermankova ◽  
Jan Kossl
Keyword(s):  
Stem Cell ◽  
Treatment Protocol ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Cell Type ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell–based therapy that could replace diseased or missing retinal cells and support regeneration. In this respect, mesenchymal stem cells (MSCs) that can be obtained from the particular patient and used as autologous cells have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of pro-inflammatory cytokines by retinal tissue, and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.

scholarly journals Nuclear envelope defects cause stem cell dysfunction in premature-aging mice

2008 ◽  
Vol 181 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Jesús Espada ◽  
Ignacio Varela ◽  
Ignacio Flores ◽  
Alejandro P. Ugalde ◽  
Juan Cadiñanos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Nuclear Envelope ◽  
Nuclear Architecture ◽  
Nuclear Lamina ◽  
Premature Aging ◽  
Molecular Signaling ◽  
Cell Dysfunction ◽  
Age Related ◽  
Microphthalmia Transcription Factor

Nuclear lamina alterations occur in physiological aging and in premature aging syndromes. Because aging is also associated with abnormal stem cell homeostasis, we hypothesize that nuclear envelope alterations could have an important impact on stem cell compartments. To evaluate this hypothesis, we examined the number and functional competence of stem cells in Zmpste24-null progeroid mice, which exhibit nuclear lamina defects. We show that Zmpste24 deficiency causes an alteration in the number and proliferative capacity of epidermal stem cells. These changes are associated with an aberrant nuclear architecture of bulge cells and an increase in apoptosis of their supporting cells in the hair bulb region. These alterations are rescued in Zmpste24−/−Lmna+/− mutant mice, which do not manifest progeroid symptoms. We also report that molecular signaling pathways implicated in the regulation of stem cell behavior, such as Wnt and microphthalmia transcription factor, are altered in Zmpste24−/− mice. These findings establish a link between age-related nuclear envelope defects and stem cell dysfunction.

scholarly journals Muscle stem cell dysfunction impairs muscle regeneration in a mouse model of Down syndrome

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Bradley Pawlikowski ◽  
Nicole Dalla Betta ◽  
Tiffany Elston ◽  
Darian A. Williams ◽  
Bradley B. Olwin
Keyword(s):  
Down Syndrome ◽  
Stem Cell ◽  
Mouse Model ◽  
Muscle Regeneration ◽  
Muscle Stem Cell ◽  
Cell Dysfunction

RELATIONSHIP BETWEEN FORWARD TRUNK LEAN DURING WALKING AND MUSCULOSKELETAL FUNCTIONS FOR FEMALES

2008 ◽  
Vol 08 (04) ◽  
pp. 459-471 ◽  
Author(s):  
HARUHIKO SATO ◽  
MURRAY E. MAITLAND
Keyword(s):  
Muscle Weakness ◽  
Thoracic Kyphosis ◽  
Fear Of Falling ◽  
Balance Control ◽  
The Elderly ◽  
Quadriceps Muscle ◽  
Knee Extension ◽  
Joint Moments ◽  
Age Related ◽  
The Mean

A forward trunk lean sometimes occurs to compensate for quadriceps muscle weakness. Since muscle weakness in the lower extremities is commonly observed in the elderly, quadriceps weakness may trigger age-related postural change. The objective of this study was to ascertain the association between forward trunk lean during walking and musculoskeletal strength in females aged between 46 and 79 years. Musculoskeletal functions (range of joint motion, degree of kyphosis, muscle strength) and joint moments during walking were measured for 13 females. Subjects who showed greater joint moments during walking tended to lean more. Moderate association was seen between mean trunk angle during walking and knee extension moment (r = 0.535, p = 0.060). There was no statistically significant correlation between the strength of the quadriceps muscle and the mean trunk angle in walking subjects (r = 0.095, p = 0.758). These observations suggested that muscle weakness in the quadriceps is largely independent of leaning of the trunk for this sample of subjects. Other factors may change the posture to a stoop, such as severe thoracic kyphosis, poor balance control, or fear of falling.

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