Stem cell aging: mechanisms, regulators and therapeutic opportunities

Oh, Juhyun; Lee, Yang David; Wagers, Amy J.

doi:10.1038/nm.3651

Cited by 615 publications

(495 citation statements)

References 190 publications

Supporting

Mentioning

480

Contrasting

Unclassified

Order By: Relevance

“…Stem cell exhaustion causes organismal aging and contributes to various aging‐associated disorders (Oh, Lee, & Wagers, 2014). We next investigated whether the metformin‐Nrf2‐GPx7 pathway also functions in HMSCs.…”

Section: Resultsmentioning

confidence: 99%

Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7

et al. 2018

View full text Add to dashboard Cite

SummaryMetformin, an FDA‐approved antidiabetic drug, has been shown to elongate lifespan in animal models. Nevertheless, the effects of metformin on human cells remain unclear. Here, we show that low‐dose metformin treatment extends the lifespan of human diploid fibroblasts and mesenchymal stem cells. We report that a low dose of metformin upregulates the endoplasmic reticulum‐localized glutathione peroxidase 7 (GPx7). GP×7 expression levels are decreased in senescent human cells, and GPx7 depletion results in premature cellular senescence. We also indicate that metformin increases the nuclear accumulation of nuclear factor erythroid 2‐related factor 2 (Nrf2), which binds to the antioxidant response elements in the GPX7 gene promoter to induce its expression. Moreover, the metformin‐Nrf2‐GPx7 pathway delays aging in worms. Our study provides mechanistic insights into the beneficial effects of metformin on human cellular aging and highlights the importance of the Nrf2‐GPx7 pathway in pro‐longevity signaling.

show abstract

Section: Resultsmentioning

confidence: 99%

Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7

et al. 2018

View full text Add to dashboard Cite

show abstract

“…21,23 The stem cell theory of aging postulates a decline in stem cell number and functionalities as a potential effect of aging. [24][25][26] Schultz and Sinclair have discussed that the probable causes of cellular aging (i.e., the abovementioned telomere attrition, DNA damage, and cellular senescence) can also be applied to stem cells. 15 Fukada et al have not only described the aging of stem cells but have also connected the other theories with the stem cell theory to explain the complex progression of aging.…”

Section: General Theories Of Agingmentioning

confidence: 99%

Age Related Changes in Bone Marrow Mesenchymal Stromal Cells: A Potential Impact on Osteoporosis and Osteoarthritis Development

et al. 2017

View full text Add to dashboard Cite

Aging at the cellular level is a complex process resulting from accumulation of various damages leading to functional impairment and a reduced quality of life at the level of the organism. With a rise in the elderly population, the worldwide incidence of osteoporosis (OP) and osteoarthritis (OA) has increased in the past few decades. A decline in the number and "fitness" of mesenchymal stromal cells (MSCs) in the bone marrow (BM) niche has been suggested as one of the factors contributing to bone abnormalities in OP and OA. It is well recognized that MSCs in vitro acquire culture-induced aging features such as gradual telomere shortening, increased numbers of senescent cells, and reduced resistance to oxidative stress as a result of serial population doublings. In contrast, there is only limited evidence that human BM-MSCs "age" similarly in vivo. This review compares the various aspects of in vitro and in vivo MSC aging and suggests how our current knowledge on rejuvenating cultured MSCs could be applied to develop future strategies to target altered bone formation processes in OP and OA.

show abstract

“…The balance between ASC proliferation and differentiation needs to be tightly regulated because any alteration can lead to depletion or overgrowth of the ASC population, resulting in premature aging or cancer (Oh et al, 2014;Visvader, 2011). The decision to either self-renew or differentiate is controlled by intrinsic determinants present in ASCs and/or extrinsic signals from neighboring differentiated tissues (Morrison and Spradling, 2008).…”

Section: Introductionmentioning

confidence: 99%

The EGFR signaling pathway controls gut progenitor differentiation during planarian regeneration and homeostasis

2016

View full text Add to dashboard Cite

The planarian Schmidtea mediterranea maintains and regenerates all its adult tissues through the proliferation and differentiation of a single population of pluripotent adult stem cells (ASCs) called neoblasts. Despite recent advances, the mechanisms regulating ASC differentiation into mature cell types are poorly understood. Here, we show that silencing of the planarian EGF receptor egfr-1 by RNA interference (RNAi) impairs gut progenitor differentiation into mature cells, compromising gut regeneration and maintenance. We identify a new putative EGF ligand, nrg-1, the silencing of which phenocopies the defects observed in egfr-1(RNAi) animals. These findings indicate that egfr-1 and nrg-1 promote gut progenitor differentiation, and are thus essential for normal cell turnover and regeneration in the planarian gut. Our study demonstrates that the EGFR signaling pathway is an important regulator of ASC differentiation in planarians.

show abstract

Stem cell aging: mechanisms, regulators and therapeutic opportunities

Cited by 615 publications

References 190 publications

Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7

Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7

Age Related Changes in Bone Marrow Mesenchymal Stromal Cells: A Potential Impact on Osteoporosis and Osteoarthritis Development

The EGFR signaling pathway controls gut progenitor differentiation during planarian regeneration and homeostasis

Contact Info

Product

Resources

About