Rejuvenating Strategies of Tissue-specific Stem Cells for Healthy Aging

Wang, Minjun; Chen, Jiajia; Chen, Fei; Liu, Qinggui; Sun, Yu; Chen, Yan; Yang, Tao; Bao, Yi-Wen; Hu, Yiping

doi:10.14336/ad.2018.1119

Cited by 21 publications

(20 citation statements)

References 111 publications

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“…These changes induce cell-autonomous aging and are potential targets for rejuvenation in aged MuSCs. Figure 3 shows major strategies targeting intracellular processes for rejuvenation in aged MuSCs [123]. Increased expression of several cell cycle inhibitors, such as p53 [124,125], p16 Ink4 [77], and p57 Kip2 [126] leads to an irreversible cell cycle arrest and promotes cellular senescence.…”

Section: Cell-autonomous Rejuvenation Strategymentioning

confidence: 99%

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Stem Cell Aging in Skeletal Muscle Regeneration and Disease

Yamakawa

Kusumoto

Hashimoto

et al. 2020

IJMS

114

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Skeletal muscle comprises 30–40% of the weight of a healthy human body and is required for voluntary movements in humans. Mature skeletal muscle is formed by multinuclear cells, which are called myofibers. Formation of myofibers depends on the proliferation, differentiation, and fusion of muscle progenitor cells during development and after injury. Muscle progenitor cells are derived from muscle satellite (stem) cells (MuSCs), which reside on the surface of the myofiber but beneath the basement membrane. MuSCs play a central role in postnatal maintenance, growth, repair, and regeneration of skeletal muscle. In sedentary adult muscle, MuSCs are mitotically quiescent, but are promptly activated in response to muscle injury. Physiological and chronological aging induces MuSC aging, leading to an impaired regenerative capability. Importantly, in pathological situations, repetitive muscle injury induces early impairment of MuSCs due to stem cell aging and leads to early impairment of regeneration ability. In this review, we discuss (1) the role of MuSCs in muscle regeneration, (2) stem cell aging under physiological and pathological conditions, and (3) prospects related to clinical applications of controlling MuSCs.

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Section: Cell-autonomous Rejuvenation Strategymentioning

confidence: 99%

“…Pharmacological interventions to promote MuSC self-renewal are of therapeutic interest to extend the limits of muscle repair with age [154]. Table 1 summarizes the non-cell autonomous rejuvenation strategies to rejuvenate aged MuSCs [123].…”

Section: Non-cell Autonomous Rejuvenation Strategymentioning

confidence: 99%

Stem Cell Aging in Skeletal Muscle Regeneration and Disease

Yamakawa

Kusumoto

Hashimoto

et al. 2020

IJMS

114

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“…Substantial evidence of the aging-associated reduction in the functions of adult stem cells prompted us to develop novel strategies for rejuvenating elderly stem cells for anti-aging research and therapies 16 . In the present study, we examined the correlation of the increased ROS levels and impaired cellular functions of elderly AT-MSCs as well as the rejuvenation of AT-MSCs by infant EVs.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic intervention includes reversing DNA damage, telomerase reactivation, epigenetic regulation (e.g. repair of DNA methylation and histone modification), all conventional approaches that have proven effective for improving the function of several types of stem cells, such as muscle, cardiac, and hematopoietic stem cells 16 . However, both pharmacological and genetic manipulation have limited efficacy, as they can only improve a few specific functions, thus requiring the manipulation of a combination of genes or pathways for a comprehensive approach to rejuvenating stem cells 15,16 .…”

mentioning

confidence: 99%

Rejuvenation of mesenchymal stem cells by extracellular vesicles inhibits the elevation of reactive oxygen species

Khánh

Yamashita

Ohneda

et al. 2020

Sci Rep

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Aging induces numerous cellular disorders, such as the elevation of reactive oxygen species (ROS), in a number type of cells, including mesenchymal stem cells (MSCs). However, the correlation of ROS and impaired healing abilities as well as whether or not the inhibition of elevating ROS results in the rejuvenation of elderly MSCs is unclear. The rejuvenation of aged MSCs has thus recently received attention in the field of regenerative medicine. Specifically, extracellular vesicles (EVs) act as a novel tool for stem cell rejuvenation due to their gene transfer ability with systemic effects and safety. In the present study, we examined the roles of aging-associated ROS in the function and rejuvenation of elderly MSCs by infant EVs. The data clearly showed that elderly MSCs exhibited the downregulation of superoxide dismutase (SOD)1 and SOD3, which resulted in the elevation of ROS and downregulation of the MEK/ERK pathways, which are involved in the impairment of the MSCs’ ability to decrease necrotic area in the skin flap model. Furthermore, treatment with the antioxidant Edaravone or co-overexpression of SOD1 and SOD3 rescued elderly MSCs from the elevation of ROS and cellular senescence, thereby improving their functions. Of note, infant MSC-derived EVs rejuvenated elderly MSCs by inhibiting ROS production and the acceleration of cellular senescence and promoting the proliferation and in vivo functions in both type 1 and type 2 diabetic mice.

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“…Loss of SC may seem difficult to repair, but with the advent of cell reprogramming strategies, 38 eventually it may become possible to replace or rejuvenate lost SC populations throughout the body. 39 Finally, given the recently uncovered roles in pathologies for SNS signaling in general and NE-mediated signaling in particular, it would not be surprising to find activation of the SNS playing key roles in numerous examples of physiological dysfunction associated with aging, and studies to uncover such mechanisms should be initiated, especially given the possibility of altering this well-studied component of the ANS with small molecule therapeutics. Moreover, the hypothesized connections of increased SNS activation with cell senescence need to be established.…”

Section: Medical Implicationsmentioning

confidence: 99%

The Danger of Being Too Sympathetic: Norepinephrine in Alzheimer's Disease and Graying of Hair

Mendelsohn

Larrick

2020

Rejuvenation Research

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Although alterations in the sympathetic nervous system (SNS) with age have been reported, and serious degenerative diseases of the autonomic nervous system such as multiple system atrophy are more likely to strike older people, connections between dysregulated adrenergic receptors and age-associated diseases and phenotypes have not been well studied. Two recent reports suggest that SNS may be more closely connected than previously appreciated. First, low nanomolar concentrations of Alzheimer's disease (AD)-associated Ab42-amyloid oligomers alter signaling by SNS neurotransmitter norepinephrine (NE) to sufficiently activate kinase GSK3b to hyperphosphorylate tau, a key mediator of neurotoxicity in AD. Connecting beta-amyloid to tau in AD has been a key quest in understanding AD and developing therapeutics. The a 2 adrenergic receptor inhibitory drug idazoxan reduces GSK3b activity and tau phosphorylation in AD mice with improved cognitive function, even in the presence of betaamyloid deposits. In this study, SNS activation in the brain coupled with problematic Ab42-amyloid oligomers result in serious consequences that can be ameliorated by reducing SNS signaling. A second example of the detrimental effects of increased SNS signaling is the premature graying of hair in response to stress. Secretion of NE resulting from stress causes differentiation of most hair pigment melanocyte stem cells (MeSCs) into melanocytes, rapidly depleting the hair follicle of pigment-producing cells as mature melanocytes undergo apoptosis and MeSCs are eventually eliminated. Blockade of NE SNS signaling preserves hair coloration in stressed animals. Increased SNS activation has serious apparently irreversible effects on homeostasis in both situations. Although neither report directly addresses aging, given that AD and the loss of hair pigmentation have strong age associations, it is of interest to better understand the role that SNS has in promoting age-associated phenotypes generally and determine if tuning the SNS through drug-mediated attenuation of SNS signaling may be of medical benefit.

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Rejuvenating Strategies of Tissue-specific Stem Cells for Healthy Aging

Cited by 21 publications

References 111 publications

Stem Cell Aging in Skeletal Muscle Regeneration and Disease

Stem Cell Aging in Skeletal Muscle Regeneration and Disease

Rejuvenation of mesenchymal stem cells by extracellular vesicles inhibits the elevation of reactive oxygen species

The Danger of Being Too Sympathetic: Norepinephrine in Alzheimer's Disease and Graying of Hair

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