The Aging Epigenome

In the paper

“Furthermore, transient, ectopic expression of a small number of transcription factors in adult mammalian cells can convert terminally differentiated cells into pluripotent stem cells or into other differentiated states (Graf, 2011).”

What the sources say

• Not checked yetcites Graf, 2011 source

In the paper

“These epigenomic changes are not only observed during aging but also profoundly affect cellular function and stress resistance, thereby contributing to the progression of aging.”

In the paper

“Over the past decades, a large body of research has shown that the molecular and cellular decline of aging can be organized into several evolutionarily conserved hallmarks or pillars of aging (Kennedy et al., 2014; López-Otín et al., 2013).”

What the sources say

• Not checked yetcites Kennedy et al., 2014 source
• Not checked yetcites López-Otín et al., 2013 source

In the paper

“This is illustrated by the fact that in Saccharomyces cerevisiae, only three transcription factors control cell identity, and their mis-expression results in cell-cycle arrest and an inability to mate (Herskowitz, 1989).”

What the sources say

• Not checked yetcites Herskowitz, 1989 source

In the paper

“Finally, non-coding RNAs have been found to play important roles in regulating chromatin states and gene expression (Rinn and Chang, 2012).”

What the sources say

• Not checked yetcites Rinn and Chang, 2012

In the paper

“Recent studies in diverse species and cell types have highlighted the pervasiveness of age-associated changes in transcription factor binding, histone marks, heterochromatin formation, and DNA methylation (recently reviewed by Benayoun et al., 2015; Zampieri et al., 2015) that contribute to changes in gene expression.”

What the sources say

• Not checked yetcites Benayoun et al., 2015 source
• Not checked yetcites Zampieri et al., 2015 source

In the paper

“Gene regulation is a natural “hub” in the cell. Transcription regulators and chromatin modifiers receive cytoplasmic and extracellular signals and, in turn, alter the responses of the cell in an orchestrated manner.”

In the paper

“Thus, age-associated changes in transcription regulatory networks are likely to impact the function of a cell or tissue and give rise to aging phenotypes and diseases.”

In the paper

“Because of their crucial role in cellular function, we propose that age-associated changes in transcriptional factors and chromatin states represent a critical aspect of the aging process and an important hub that links many hallmarks of aging.”

In the paper

“FOXO/DAF-16 promotes longevity and inhibits age-related diseases in species ranging from worms to humans (Eijkelenboom and Burgering, 2013; Salih and Brunet, 2008).”

What the sources say

• Not checked yetcites Eijkelenboom and Burgering, 2013
• Not checked yetcites Salih and Brunet, 2008

In the paper

“For example, in yeast and animals, mitochondrial dysfunction increases with age and may contribute to the progression of aging (Sun et al., 2016).”

What the sources say

• Not checked yetcites Sun et al., 2016 source

In the paper

“The hallmarks of aging are interconnected (Kennedy et al., 2014; López-Otín et al., 2013; Zhang et al., 2015a), and age-associated perturbations of one can affect others.”

What the sources say

• Not checked yetcites Kennedy et al., 2014 source
• Not checked yetcites López-Otín et al., 2013 source
• Not checked yetcites Zhang et al., 2015a

In the paper

“In addition, KDM6B/JMJD-3.1 and PHF8/JMJD-1.2 are necessary for lifespan extension induced by mitochondrial dysfunction, and overexpression of either of these genes extends lifespan in C. elegans (Merkwirth et al., 2016).”

What the sources say

• Not checked yetcites Merkwirth et al., 2016 source

In the paper

“Importantly, both FOXO/DAF-16 and NRF/SKN-1 not only promote changes in chromatin state (Riedel et al., 2013; Zaret and Carroll, 2011; Zhang et al., 2006) but also are sensitive to them (Domcke et al., 2015; Eijkelenboom et al., 2013; Webb et al., 2013).”

What the sources say

• Not checked yetcites Riedel et al., 2013 source
• Not checked yetcites Zaret and Carroll, 2011
• Not checked yetcites Zhang et al., 2006 source

In the paper

“Classically considered to control the transcriptional response to oxidative stress, NRF/SKN-1 has also been implicated in general detoxification, proteostasis, and immunity (Blackwell et al., 2015).”

What the sources say

• Not checked yetcites Blackwell et al., 2015 source

In the paper

“Interestingly, mice with higher PHF8/JMJD-1.2 expression are longer lived, suggesting that the link between PHF8/JMJD-1.2 and longevity might be conserved from invertebrates to mammals (Merkwirth et al., 2016).”

What the sources say

• Not checked yetcites Merkwirth et al., 2016 source

In the paper

“Thus, FOXO/DAF-16 regulates a program of genes whose major function is to promote stress resistance, and this may be linked with their ability to extend lifespan.”

In the paper

“Like FOXO/DAF-16, NRF/SKN-1 is a “pro-longevity” transcription factor. Indeed, increasing the level of active NRF/SKN-1 extends lifespan in flies and worms (Sykiotis and Bohmann, 2008; Tullet et al., 2008).”

What the sources say

• Not checked yetcites Sykiotis and Bohmann, 2008
• Not checked yetcites Tullet et al., 2008 source

In the paper

“Together, these studies show that NRF/SKN-1 is an important regulator of stress resistance and that its activity is intimately linked with chromatin state.”

In the paper

“Knockdown of the H3K27me3 demethylase UTX-1 increases lifespan in C. elegans (Jin et al., 2011; Maures et al., 2011; Ni et al., 2012), suggesting that H3K27me3 levels are beneficial for longevity.”

What the sources say

• Not checked yetcites Jin et al., 2011 source
• Not checked yetcites Maures et al., 2011 source
• Not checked yetcites Ni et al., 2012

In the paper

“In mammals, NRF2 recruits BRG2, a component of the SWI/SNF nucleosome remodeling complex, to its regulatory targets (Zhang et al., 2006). This interaction results in increased transcriptional activation of stress-response genes (Zhang et al., 2006), presumably through changes in the chromatin landscape.”

What the sources say

• Not checked yetcites Zhang et al., 2006 source

In the paper

“In mice, loss of Utx is associated with severe developmental defects in females, but not males, and a shortened male lifespan (Welstead et al., 2012).”

What the sources say

• Not checked yetcites Welstead et al., 2012 source

In the paper

“Furthermore, loss of components of Polycomb, the H3K27 methyltransferase, increases lifespan in male Drosophila, suggesting that increased levels of H3K27me3 are detrimental for male lifespan (Siebold et al., 2010).”

What the sources say

• Not checked yetcites Siebold et al., 2010 source

In the paper

“Indeed, FOXO has been found to bind open chromatin, especially at enhancer regions (Eijkelenboom et al., 2013; Webb et al., 2013), and can act as a pioneer factor to open closed chromatin (Zaret and Carroll, 2011).”

What the sources say

• Not checked yetcites Eijkelenboom et al., 2013
• Not checked yetcites Webb et al., 2013 source
• Not checked yetcites Zaret and Carroll, 2011

In the paper

“In contrast, overexpression of the H3K27me3 demethylase KDM6B/JMJD-3.1 extends lifespan, suggesting that an increased level of H3K27me3 at specific loci (stress-response genes) is detrimental for lifespan (Labbadia and Morimoto, 2015).”

What the sources say

• Not checked yetcites Labbadia and Morimoto, 2015

In the paper

“Intriguingly, DNA methylation patterns can serve as a biomarker for human chronological age (Horvath, 2013), and perhaps even biological age (i.e., how youthful or decrepit an individual actually is at a particular age).”

What the sources say

• Not checked yetcites Horvath, 2013 source

In the paper

“While hypomethylation is common with age, some CpG islands and gene-rich regions become hypermethylated with age (reviewed by Benayoun et al., 2015; Zampieri et al., 2015).”

What the sources say

• Not checked yetcites Benayoun et al., 2015 source
• Not checked yetcites Zampieri et al., 2015 source

In the paper

“During aging, the changes in histone mark patterning and levels could be the result of age-associated changes in the activity of transcription factors, either through changes in the expression of the components of histone-modifying complexes or through the differential recruitment of these complexes to chromatin.”

In the paper

“Interestingly, low levels of H3K36me3 are correlated with increased cryptic transcription (Sen et al., 2015) and a greater degree of gene expression change with age (Pu et al., 2015).”

What the sources say

• Not checked yetcites Sen et al., 2015 source
• Not checked yetcites Pu et al., 2015

In the paper

“Interestingly, the loci that display age-dependent DNA hypermethylation are preferentially near tissue-specific genes, genes involved in differentiation and development, genes encoding transcription factors, and transcription factor binding sites (reviewed by Benayoun et al., 2015; Zampieri et al., 2015).”

What the sources say

• Not checked yetcites Benayoun et al., 2015 source
• Not checked yetcites Zampieri et al., 2015 source

In the paper

“In mammals, the genome-wide pattern of DNA methylation changes during aging (Figure 2), and these changes could play a role in the progression of aging (Benayoun et al., 2015; Zampieri et al., 2015).”

What the sources say

• Not checked yetcites Benayoun et al., 2015 source
• Not checked yetcites Zampieri et al., 2015 source

In the paper

“Global H3K27me3 increases with age in the killifish brain and mouse quiescent satellite cells (Baumgart et al., 2014; Liu et al., 2013) but decreases with age during C. elegans aging and in human progeria models (Maures et al., 2011; Ni et al., 2012; Shumaker et al., 2006; Zhang et al., 2015b).”

What the sources say

• Not checked yetcites Baumgart et al., 2014 source
• Not checked yetcites Liu et al., 2013 source
• Not checked yetcites Maures et al., 2011 source

In the paper

“H3K4me3, a mark associated with active transcription, has also been implicated in longevity, and its deposition changes with age in murine hematopoietic stem cells and in Drosophila (Sun et al., 2014; Wood et al., 2010) and cellular senescence in human fibroblasts (Shah et al., 2013).”

What the sources say

• Not checked yetcites Sun et al., 2014 source
• Not checked yetcites Wood et al., 2010 source
• Not checked yetcites Shah et al., 2013 source

In the paper

“However, it has also been found that knockdown of the H3K4me3 demethylases (KDM5B/RBR-2 and KDM1A/LSD-1) can extend lifespan, often in the context of sterility (Lee et al., 2003; McColl et al., 2008; Ni et al., 2012), or has no effect on lifespan (Li et al., 2010).”

What the sources say

• Not checked yetcites Lee et al., 2003 source
• Not checked yetcites McColl et al., 2008 source
• Not checked yetcites Ni et al., 2012

In the paper

“Consistent with this finding, deletion of the H3K36me3 demethylase extends lifespan in S. cerevisiae and C. elegans (Ni et al., 2012; Sen et al., 2015), whereas deletion of the H3K36 methyltransferase (met-1) in C. elegans shortens lifespan (Pu et al., 2015).”

What the sources say

• Not checked yetcites Ni et al., 2012
• Not checked yetcites Sen et al., 2015 source
• Not checked yetcites Pu et al., 2015

In the paper

“A comparison of H3K27me3 deposition in young versus old murine hematopoietic stem cells revealed that while H3K27me3 levels increased at most loci, there were also loci with decreased H3K27me3 levels with age (Sun et al., 2014).”

What the sources say

• Not checked yetcites Sun et al., 2014 source

In the paper

“Excitingly, chromatin and transcription regulation have been found to play key roles in the age-dependent manifestation of these hallmarks of aging and in the response to their emergence (Figure 3).”

In the paper

“Thus, the potential gene expression effects of age-associated differential DNA methylation are likely to be context dependent and may require local changes in histones marks and transcription factor binding to occur before gene expression changes are observed.”

In the paper

“Interestingly, nucleosome occupancy changes have also been demonstrated to be associated with the global upregulation of gene expression with age in yeast (Hu et al., 2014) and increased transcription factor (FOXA2) binding in aged mammalian livers (Bochkis et al., 2014).”

What the sources say

• Not checked yetcites Hu et al., 2014
• Not checked yetcites Bochkis et al., 2014 source

In the paper

“With age, telomere attrition occurs, somatic DNA mutations accumulate, and transposons activate. There is also an increase in the rate of chromosomal abnormalities, some of which are oncogenic.”

What the sources say

• Not checked yetcites López-Otín et al., 2013 source
• Not checked yetcites Vijg and Suh, 2013

In the paper

“Nucleosome occupancy can decrease with age (Figure 2), and ameliorating this loss in yeast increases lifespan (Feser et al., 2010; Hu et al., 2014; Ivanov et al., 2013).”

What the sources say

• Not checked yetcites Feser et al., 2010 source
• Not checked yetcites Hu et al., 2014
• Not checked yetcites Ivanov et al., 2013 source

In the paper

“Importantly, during normal aging in humans and invertebrates, HP1 and H3K9me3 levels also decline (Figure 2), suggesting that loss of heterochromatin is a common feature of aging (Larson et al., 2012; Ni et al., 2012; Scaffidi and Misteli, 2006; Wood et al., 2010).”

What the sources say

• Not checked yetcites Larson et al., 2012 source
• Not checked yetcites Ni et al., 2012
• Not checked yetcites Scaffidi and Misteli, 2006

In the paper

“Intriguingly, it was recently discovered that the autophagosome can selectively degrade the endoplasmic reticulum and the nucleus (Mochida et al., 2015), and that this degradation can lead to a loss of the nuclear lamina (Dou et al., 2015).”

What the sources say

• Not checked yetcites Mochida et al., 2015 source
• Not checked yetcites Dou et al., 2015 source

In the paper

“Interestingly, the nuclear envelope may play a role in heterochromatin loss in both normal and progeroid aging: the levels of a cryptic splice isoform that results in a truncated nuclear envelope protein lamin A, and that mimics the mutation of HGPS, increase with age in humans and contribute to the loss of heterochromatin (Scaffidi and Misteli, 2006).”

What the sources say

• Not checked yetcites Scaffidi and Misteli, 2006

In the paper

“However, at least in the case of aged β cells, a significant correlation between DNA methylation and gene expression changes exists for distal regulatory regions (enhancers), but not proximal regulatory regions (promoters) (Avrahami et al., 2015).”

What the sources say

• Not checked yetcites Avrahami et al., 2015 source

In the paper

“However, in mammalian muscle stem cells, the loss of core histones with age appears to be due to changes in gene expression and is linked with the amount of the repressive H3K27me3 mark at the histone genes (Liu et al., 2013).”

What the sources say

• Not checked yetcites Liu et al., 2013 source

In the paper

“Together, these studies show that the positioning of nucleosomes on DNA changes with age and that changes in transcription factor activity and the chromatin landscape can trigger these changes during aging.”

In the paper

“Interestingly, damaged telomeres can also lead to a reduction in the expression of core histones in a cell, suggesting that a loss of telomere integrity can cause changes in the aging chromatin landscape (O’Sullivan et al., 2010).”

What the sources say

• Not checked yetcites O’Sullivan et al., 2010 source

In the paper

“these large-scale chromosomal abnormalities are distinct from other aspects of genome instability, such as mutation accumulation, in both their molecular origin and sensitivity to DNA methylation changes.”

In the paper

“This raises the possibility that age-dependent DNA hypermethylation (increased DNA methylation) at specific loci contributes to the accumulation of point mutations during aging.”

In the paper

“In murine embryonic stem cells, DNA damage relocates the transcriptional silencer SIRT1 from promoters to the site of DNA damage and changes gene expression in a way that resembles organismal aging (Oberdoerffer et al., 2008).”

What the sources say

• Not checked yetcites Oberdoerffer et al., 2008 source

In the paper

“It is important to note, however, that in yeast the rate of age-associated mutation accumulation is low, and thereby is unlikely to play a major role in the progression of aging (Kaya et al., 2015).”

What the sources say

• Not checked yetcites Kaya et al., 2015 source

In the paper

“in yeast, the loss of nucleosomes with age is associated with increased expression (and perhaps increased retrotransposition) of the Ty retrotransposable element (Hu et al., 2014).”

What the sources say

• Not checked yetcites Hu et al., 2014

In the paper

“The recruitment of SIRT6 to sites of DNA damage helps to remodel the local chromatin environment through deacetylation of H3K56 and allow DNA repair machinery to access the DNA (Toiber et al., 2013).”

What the sources say

• Not checked yetcites Toiber et al., 2013 source

In the paper

“Deletion of SIRT6 causes more rapid aging in mice and increased genomic instability (Mostoslavsky et al., 2006), suggesting that changes in SIRT6 activity and H3K56 acetylation during normal aging could impact the cell’s ability to repair DNA damage.”

What the sources say

• Not checked yetcites Mostoslavsky et al., 2006 source

In the paper

“mutations in mtDNA, and changes inmitochondrial biogenesis have been functionally implicated in the progression of aging (reviewed by Sun et al., 2016).”

What the sources say

• Not checked yetcites Sun et al., 2016 source

In the paper

“This suggests that an accumulation of DNA damage and loss of SIRT1 repression may underlie age-associated epigenomic changes.”

In the paper

“As cells age, mitochondrial turnover declines and mitochondrial dysfunction increases (Sun et al., 2016).”

What the sources say

• Not checked yetcites Sun et al., 2016 source

In the paper

“Interestingly, during human aging, mutations accumulate in the genome of blood cells and C-to-T mutations are the most prevalent (Welch et al., 2012).”

What the sources say

• Not checked yetcites Welch et al., 2012 source

In the paper

“Consistent with a link between longevity and telomere silencing, older yeast have less active Sir2 (a sirtuin) and, as a result, increased H4K16 acetylation at telomeres (Dang et al., 2009).”

What the sources say

• Not checked yetcites Dang et al., 2009 source

In the paper

“DNA damage can result in transient gene repression (Kim et al., 2016) as well as more stable changes in gene expression that can be observed in humans as young as 40 years of age (Lu et al., 2004).”

What the sources say

• Not checked yetcites Kim et al., 2016 source
• Not checked yetcites Lu et al., 2004

In the paper

“In yeast, signals from the mitochondria can trigger gene expression changes in the nucleus (retrograde regulation), and this regulation is required for the longer replicative lifespan of yeast lacking mtDNA (Kirchman et al., 1999).”

What the sources say

• Not checked yetcites Kirchman et al., 1999 source

In the paper

“Interestingly, sensing and responding to DNA damage involves the recruitment of chromatin modifiers, suggesting that an accumulation of DNA damage during life could be a source for age-associated epigenomic changes and that changes in chromatin state could affect DNA repair (Burgess et al., 2012; Oberdoerffer and Sinclair, 2007).”

What the sources say

• Not checked yetcites Burgess et al., 2012 source
• Not checked yetcites Oberdoerffer and Sinclair, 2007 source

In the paper

“the UPRmt responds to unbalanced levels of nuclear:mitochondrial-encoded oxidative phosphorylation enzymes, mtDNA depletion, and decline of the respiratory chain (Schulz and Haynes, 2015).”

What the sources say

• Not checked yetcites Schulz and Haynes, 2015

In the paper

“In C. elegans, the XBP-1 branch of the UPRER declines relatively early with age and overexpression of XBP-1 in neurons can extend lifespan, suggesting an important role for the UPRER in longevity (reviewed by Taylor, 2016).”

What the sources say

• Not checked yetcites Taylor, 2016 source

In the paper

“XBP1 and the UPRER have also been found to play a role in human neurodegenerative diseases, including Alzheimer’s disease, where UPRER/XBP1 activation is thought to be neuroprotective early in the disease onset but then a contributor to neuronal death during later disease stages (reviewed by Taylor, 2016).”

What the sources say

• Not checked yetcites Taylor, 2016 source

In the paper

“overexpression of the H3K27me3 demethylase KDM6B/JMJD-3.1 extends C. elegans lifespan and improves stress tolerance (Labbadia and Morimoto, 2015).”

What the sources say

• Not checked yetcites Labbadia and Morimoto, 2015

In the paper

“Proteostasis and the HSF-1 response decline with age (Labbadia and Morimoto, 2014).”

What the sources say

• Not checked yetcites Labbadia and Morimoto, 2014 source

In the paper

“This change occurs at the very beginning of adulthood and, similar to DAF-16 regulation, may be linked to signals from the germline (Hsin and Kenyon, 1999; Labbadia and Morimoto, 2015).”

What the sources say

• Not checked yetcites Hsin and Kenyon, 1999
• Not checked yetcites Labbadia and Morimoto, 2015

In the paper

“This suggests the exciting idea that epigenomic changes are one of the first to occur during aging and that these changes trigger the emergence of other hallmarks of aging (Labbadia and Morimoto, 2015).”

What the sources say

• Not checked yetcites Labbadia and Morimoto, 2015

In the paper

“In mammals, additional transcription factors, including SRF and HSF2, are important contributors to the transcriptional response to heat shock (Mahat et al., 2016).”

What the sources say

• Not checked yetcites Mahat et al., 2016 source

In the paper

“REST, and its invertebrate ortholog SPR-4, protects neurons from amyloid β-protein toxicity as well as oxidative stress (Lu et al., 2014).”

What the sources say

• Not checked yetcites Lu et al., 2014

In the paper

“Clearing senescent cells from adult mice by inducing apoptosis with the drug ABT263 or an inducible transgene rejuvenates hematopoietic and muscle stem cells, slows the onset of age-related disease, and increases lifespan (Baker et al., 2016; Chang et al., 2016).”

What the sources say

• Not checked yetcites Baker et al., 2016 source
• Not checked yetcites Chang et al., 2016 source

In the paper

“An increase in the number of senescent cells and a decline in tissue regeneration due to the loss of stem cell proliferation are both hallmarks of aging (López-Otín et al., 2013).”

What the sources say

• Not checked yetcites López-Otín et al., 2013 source

In the paper

“nuclear lamin defects can activate p53 and induce expression of p53 target genes (Varela et al., 2005).”

What the sources say

• Not checked yetcites Varela et al., 2005 source

In the paper

“knockdown of the histone acetyltransferase p300 results in hypoacetylation of histones H3 and H4 and an increase in senescence in human cells, providing evidence for a causative link between changes in chromatin state and senescence (Prieur et al., 2011).”

What the sources say

• Not checked yetcites Prieur et al., 2011 source

In the paper

“a recent study using human brain tissue identified dysregulation of the transcription factor REST (also known as NRSF) as a key, early event in the development of Alzheimer’s disease (Lu et al., 2014).”

What the sources say

• Not checked yetcites Lu et al., 2014

In the paper

“Changes in the availability of NAD+ during aging can affect the activity of the sirtuins, yielding altered gene expression and chromatin state with age.”

In the paper

“Thus, appropriate regulation of the transcription factor p53 is key for longevity, and its dysregulation can lead to more rapid aging and increased senescence.”

In the paper

“in mammals, p300/CBP also acts as a CREB co-activator through histone acetylation (e.g., H3K27ac and H3K14ac), suggesting a link between nutrient sensing, chromatin, and gene expression (Altarejos and Montminy, 2011).”

What the sources say

• Not checked yetcites Altarejos and Montminy, 2011

In the paper

“Patients with the progeroid diseases HGPS and Werner syndrome have abnormally high levels of senescent cells and low proliferative potential, and these changes are thought to be the result of a loss of lamin-associated heterochromatin (Shumaker et al., 2006; Zhang et al., 2015b).”

What the sources say

• Not checked yetcites Shumaker et al., 2006 source
• Not checked yetcites Zhang et al., 2015b

In the paper

“SIRT1 activity is circadian, and through an interaction with components of the circadian transcription regulatory network and an H3K4 methyltransferase, SIRT1 helps to control circadian gene expression patterns (Aguilar-Arnal et al., 2015; Orozco-Solis and Sassone-Corsi, 2014).”

What the sources say

• Not checked yetcites Aguilar-Arnal et al., 2015 source
• Not checked yetcites Orozco-Solis and Sassone-Corsi, 2014

In the paper

“the activity of these transcription factors increases with age in humans, and reducing NF-κB activity ameliorates mouse models of progeria and reverses age-associated pathology (O’Brown et al., 2015; Tilstra et al., 2011).”

What the sources say

• Not checked yetcites O’Brown et al., 2015 source
• Not checked yetcites Tilstra et al., 2011

In the paper

“the H3K4 methyltransferase MLL1 is required for expression of SASP-related genes and promotes increased inflammation (Capell et al., 2016).”

What the sources say

• Not checked yetcites Capell et al., 2016 source

In the paper

“NF-κB activates the expression of the H3K27me3 demethylase Jmjd3 in immune cells, leading to a loss of H3K27me3 (De Santa et al., 2007).”

What the sources say

• Not checked yetcites De Santa et al., 2007 source

In the paper

“Genetic and environmental manipulations that perturb circadian rhythm shorten lifespan and result in metabolic defects and diseases including obesity and diabetes (Kondratov, 2007).”

What the sources say

• Not checked yetcites Kondratov, 2007 source

In the paper

“Reprogramming cells from elderly humans (as old as 101 years of age) into pluripotent cells erases many of the hallmarks of aging and restores a youthful gene expression profile that is maintained during differentiation (Lapasset et al., 2011; Mertens et al., 2015).”

What the sources say

• Not checked yetcites Lapasset et al., 2011 source
• Not checked yetcites Mertens et al., 2015 source

In the paper

“The induction of pluripotency and the trans-differentiation of cells require different sets of transcription factors (Graf, 2011) and are thus likely to result in distinct changes in transcriptional networks and chromatin state.”

What the sources say

• Not checked yetcites Graf, 2011 source

In the paper

“Epigenetic state (including chromatin marks and gene expression) are highly responsive to the environment, and, therefore, one might expect that exposure to more youthful circulating factors could reverse or slow the appearance of age-related epigenetic changes.”

In the paper

“when cells derived from patients with the progeria disease HGPS were treated with the drug Remodelin, the cells had improved nuclear architecture and increased chromatin compaction, consistent with a gain of heterochromatin (Larrieu et al., 2014).”

What the sources say

• Not checked yetcites Larrieu et al., 2014 source

In the paper

“The ability of an old nucleus to become pluripotent and youthful again is a phenomenon that occurs as a result of fertilization and that can be mimicked in the lab through nuclear transfer or by inducing pluripotency through the expression of particular transcription factors (Rando and Chang, 2012).”

What the sources say

• Not checked yetcites Rando and Chang, 2012 source

In the paper

“This suggests that reprogramming can reset the aging clock even for very old cells and could indicate that there is no point during aging when this therapeutic would not be effective (Figure 4).”

In the paper

“it is possible that these drugs could be utilized to slow the progression of aging or to treat age-related diseases.”

In the paper

“Gene regulation is a crucial hub in this network”

In the paper

“The effects of caloric restriction can be long lasting and even be passed on to the next generation (Fontana and Partridge, 2015).”

What the sources say

• Not checked yetcites Fontana and Partridge, 2015 source

In the paper

“Many of the molecular signatures of aging, including stem cell exhaustion, altered intercellular signaling, and a loss of genome integrity, are reversed in an old mouse as a result of heterochronic parabiosis, suggesting that the epigenome and gene expression could also be restored to a more youthful state by this treatment (Rando and Chang, 2012; Sinha et al., 2014)”

What the sources say

• Not checked yetcites Rando and Chang, 2012 source
• Not checked yetcites Sinha et al., 2014 source

In the paper

“the initiation timing and duration of these metabolic interventions (exercise and diet changes) can alter their effect on longevity, suggesting that context is an important factor and that these are not “one size fits all” interventions (Fontana and Partridge, 2015).”

What the sources say

• Not checked yetcites Fontana and Partridge, 2015 source

In the paper

“There are also drugs, such as rapamycin and metformin, that are able to mimic the effects of exercise and diet changes (Mercken et al., 2012).”

What the sources say

• Not checked yetcites Mercken et al., 2012 source

In the paper

“Exercise and dietary changes, including caloric restriction and intermittent fasting, can slow and even reverse the progression of aging (Brandhorst et al., 2015; Fontana and Partridge, 2015; Garatachea et al., 2015; Mercken et al., 2012)”

What the sources say

• Not checked yetcites Brandhorst et al., 2015 source
• Not checked yetcites Fontana and Partridge, 2015 source
• Not checked yetcites Garatachea et al., 2015 source

In the paper

“Changes in diet and exercise impact the activity of various longevity regulatory mechanisms, including insulin/IGF signaling and the nutrient-sensing kinase AMPK, and can alter the expression of many genes (Fontana and Partridge, 2015; Garatachea et al., 2015).”

What the sources say

• Not checked yetcites Fontana and Partridge, 2015 source
• Not checked yetcites Garatachea et al., 2015 source

In the paper

“aging is the result of dysfunction of a complex network that maintains organismal health, tissue homeostasis, and stress resistance.”

In the paper

“epigenomic regulation is highly connected to the other hallmarks of aging, and dysregulation of gene expression and the epigenome promote the progression of aging.”

In the paper

“age-associated gene expression changes have recently been identified at the single-cell level in hematopoietic stem and progenitor cells (Kowalczyk et al., 2015), suggesting that at least for some tissues, changes in the cellular composition of a tissue with age cannot fully explain age-associated epigenomic dysregulation.”

What the sources say

• Not checked yetcites Kowalczyk et al., 2015 source

In the paper

“suggests that unique molecular mechanisms may underlie the exceptionally long or short lifespans found in nature”

In the paper

“Interestingly, the evolution of transcription regulatory networks is a rich source of phenotypic diversity (Carroll, 2008).”

What the sources say

• Not checked yetcites Carroll, 2008 source

In the paper

“age-associated changes in gene regulation could in turn trigger the emergence of other hallmarks of aging in a snowball effect (Figure 4).”

In the paper

“two mechanisms could underlie the observed, age-associated epigenomic changes: (1) the exact cellular composition of a tissue or organism may change with age (even within highly purified populations of cells), and/or (2) the gene expression and chromatin state within the cells that normally reside in a particular tissue may change.”

In the paper

“changes in one generation could even influence the gametes and perhaps be passed on to next generations (Lim and Brunet, 2013).”

What the sources say

• Not checked yetcites Lim and Brunet, 2013

In the paper

“many more chromatin marks and even transcription factor families are still being discovered (Lohse et al., 2010; Luo et al., 2015).”

What the sources say

• Not checked yetcites Lohse et al., 2010 source
• Not checked yetcites Luo et al., 2015 source

In the paper

“The diversity of lifespans between species, even closely related species, illustrates that aging and longevity evolve”