The aging signature: a hallmark of induced pluripotent stem cells?

Abstract

The discovery that somatic cells can be induced into a pluripotent state by the expression of reprogramming factors has enormous potential for therapeutics and human disease modeling. With regard to aging and rejuvenation, the reprogramming process resets an aged, somatic cell to a more youthful state, elongating telomeres, rearranging the mitochondrial network, reducing oxidative stress, restoring pluripotency, and making numerous other alterations. The extent to which induced pluripotent stem cell (iPSC)s mime embryonic stem cells is controversial, however, as iPSCs have been shown to harbor an epigenetic memory characteristic of their tissue of origin which may impact their differentiation potential. Furthermore, there are contentious data regarding the extent to which telomeres are elongated, telomerase activity is reconstituted, and mitochondria are reorganized in iPSCs. Although several groups have reported that reprogramming efficiency declines with age and is inhibited by genes upregulated with age, others have successfully generated iPSCs from senescent and centenarian cells. Mixed findings have also been published regarding whether somatic cells generated from iPSCs are subject to premature senescence. Defects such as these would hinder the clinical application of iPSCs, and as such, more comprehensive testing of iPSCs and their potential aging signature should be conducted.

Blockade of senescence‐associated micro RNA ‐195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells.

“…3A) as reported in earlier findings (Li et al ., 2009; Kim et al ., 2010; Cheng et al ., 2011; Wang et al ., 2011; Rohani et al ., 2014). We reprogrammed SkMs from both young and old mice using classic Yamanaka factors, and colonies were stained with alkaline phosphatase (ALP) on day 16–18 and counted to assess reprogramming efficiency.…”

“…Previous studies have shown that older and senescent cells are more resistant to reprogramming (Li et al ., 2009; Kim et al ., 2010; Cheng et al ., 2011; Wang et al ., 2011; Rohani et al ., 2014). These observations have established the importance of current efforts underway to understand the biology of cell reprogramming in the context of chronological and replicative age.…”

“…Unlike ESCs, iPSCs are not subject to immune rejection because they are derived from a patient's own cells (Isobe et al ., 2014), and present no ethical harvesting concerns related to the obtaining human ESCs for derivation. Although murine studies reveal that cell reprogramming efficiency declines with age, the potential to generate iPSCs from a patient's own cells has emerged as a promising strategy for autologous cell‐based therapy (Li et al ., 2009; Kim et al ., 2010; Cheng et al ., 2011; Wang et al ., 2011; Rohani et al ., 2014). …”

Autosomal Recessive Bestrophinopathy Is Not Associated With the Loss of Bestrophin-1 Anion Channel Function in a Patient With a NovelBEST1Mutation

“…In addition to representing great therapeutic potential, iPSC-derived cells have proven to be very useful tools for understanding disease pathogenesis. 27,35 For these studies, we used an iPSC line (006-BIOTR-0001) obtained from the Mayo Clinic Center for Regenerative Medicine BioTrust. The successful generation of iPSCs from somatic skin fibroblasts was confirmed by the presence of the pluripotency markers Oct4, SSeA4, Nanog, Tra1-60, and Sox1 ( Supplementary Figs.…”

Recent Developments in Cardiovascular Stem Cells

“…100,101 As a result, resident cardiac stem/progenitor cells in older humans are expected to have a decreased reparative capacity in response to myocardial injury. Consequently, there is considerable interest in rejuvenating the endogenous CPCs.…”