Stem Cell Aging and Sex: Are We Missing Something?

Dulken, Ben W.; Brunet, Anne

doi:10.1016/j.stem.2015.05.006

Cited by 21 publications

(16 citation statements)

References 9 publications

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“…Several reports have indicated that adult stem cell populations ( i.e . HSCs, NSCs, MuSCs) show increased self-renewal and regenerative capacity in females compared to males (226). Moreover, females exhibit increased abilities for wound healing and liver regeneration (226).…”

Section: General Discussion and Implicationsmentioning

confidence: 99%

Multi-level remodeling of transcriptional landscapes in aging and longevity

Lai

Danthi

et al. 2019

BMB Rep.

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In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First, we discuss age-related transcriptional changes in protein-coding genes, the expected functional impact of such changes, and how known pro-longevity interventions impact these changes. Second, we discuss the changes and impact of emerging aspects of transcription in aging, including age-related changes in splicing, lncRNAs and circRNAs. Third, we discuss the changes and potential impact of transcription of transposable elements with aging. Fourth, we highlight small ncRNAs and their potential impact on the regulation of aging phenotypes. Understanding the aging transcriptome will be key to identify important regulatory targets, and ultimately slow-down or reverse aging and extend healthy lifespan in humans.

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Section: General Discussion and Implicationsmentioning

confidence: 99%

Multi-level remodeling of transcriptional landscapes in aging and longevity

Lai

Danthi

et al. 2019

BMB Rep.

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“…With PKAcatα being an essential regulator in learning and memory by transducing synaptic responses through CREB signalling 64 , 65 and controlling synaptic incorporation of AMPA receptors 66 , PKA-activity may directly contribute to the neuroprotective effects observed here. Although being a matter of debate, sex-dependencies in stem cell biology have already been shown in terms of autosomal gene expression 67 and proliferation 68 , particularly regarding mouse NSCs 69 , 70 . Compared to their male counterparts, female muscle-derived stem cells were reported to have higher muscle regeneration efficiency in mice 71 .…”

Section: Discussionmentioning

confidence: 99%

NF-κB p65 directs sex-specific neuroprotection in human neurons

Ruiz-Perera

Schneider

Windmöller

et al. 2018

Sci Rep

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Protection of neurons against oxidative stress is crucial during neuronal development, maintenance and for treating neurodegenerative diseases. However, little is known about the molecular mechanisms underlying sex-specific maturation and survival of neurons. In the present study, we demonstrate NF-κB-p65 mediated neuroprotection in human glutamatergic neurons differentiated from inferior turbinate stem cells (ITSCs) in a sex-dependent manner. We successfully differentiated ITSCs into MAP-2+/NF200+/Synaptophysin+/vGlut2+-glutamatergic neurons in vitro and ex vivo and validated their functionality. TNF-α-dependent NF-κB-p65 activation was accompanied by significant neuroprotection against oxidative stress-induced neuronal death, which was surprisingly higher in neurons from female donors. Accordingly, sex-specific neuroprotection of female neurons was followed by an increased expression of special NF-κB target genes SOD2 and IGF2. Among these, SOD2 is a well known gene protecting cells against oxidative stress resulting in longevity. In addition, IGF2 is known to promote synapse formation and spine maturation, and it has antioxidant and neuroprotective effects against oxidative damage. In conclusion, we show that NF-κB-p65 is a key player in neuroprotection of human neurons, however the protective gene expression program beneath it differs between sexes. Our findings are in accordance with the increasing evidences pointing towards sex-specific differences in risk and severity of neurodegenerative diseases.

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“…The SKL level declines with age , while the number of senescent and dysfunctional stem cells increases with age . Aging impairs stem cell proliferation , and stem cell proliferation and differentiation decrease in an age‐dependent manner . The number of stem cells is decreased while the percentage of the senescent progenitor cells is increased in tissues and organs in KL (–/–) mice .…”

Section: Discussionmentioning

confidence: 99%

The Antiaging Gene Klotho Regulates Proliferation and Differentiation of Adipose-Derived Stem Cells

Fan

Sun

2016

Stem Cells

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Klotho was originally discovered as an aging-suppressor gene. The purpose of this study was to investigate whether secreted Klotho (SKL) affects the proliferation and differentiation of adipose-derived stem cells (ADSCs). RT-PCR and Western blot analysis showed that short-form Klotho was expressed in mouse ADSCs. The Klotho gene mutation KL(−/−) significantly decreased proliferation of ADSCs and expression of pluripotent transcription factors (Nanog, Sox-2, and Oct-4) in mice. The adipogenic differentiation of ADSCs was also decreased in KL(−/−) mice. Incubation with Klotho-deficient medium decreased ADSC proliferation, pluripotent transcription factor levels, and adipogenic differentiation, which is similar to what was found in KL(−/−) mice. These results indicate that Klotho deficiency suppresses ADSC proliferation and differentiation. Interestingly, treatment with recombinant SKL protein rescued the Klotho deficiency-induced impairment in ADSC proliferation and adipogenic differentiation. SKL also regulated ADSCs’ differentiation to other cell lineages (osteoblasts, myofibroblasts), indicating that SKL maintains stemness of ADSCs. It is intriguing that overexpression of SKL significantly increased PPAR-γ expression and lipid formation in ADSCs following adipogenic induction, indicating enhanced adipogenic differentiation. Overexpression of SKL inhibited expression of TGFβ1 and its downstream signaling mediator Smad2/3. This study demonstrates, for the first time, that SKL is essential to the maintenance of normal proliferation and differentiation in ADSCs. Klotho regulates adipogenic differentiation in ADSCs, likely via inhibition of TGFβ1 and activation of PPAR-γ.

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Stem Cell Aging and Sex: Are We Missing Something?

Cited by 21 publications

References 9 publications

Multi-level remodeling of transcriptional landscapes in aging and longevity

Multi-level remodeling of transcriptional landscapes in aging and longevity

NF-κB p65 directs sex-specific neuroprotection in human neurons

The Antiaging Gene Klotho Regulates Proliferation and Differentiation of Adipose-Derived Stem Cells

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