The Aging Epigenome

In the paper

“Changes in transcriptional networks and chromatin state lie at the heart of age-dependent decline.”

In the paper

“We propose that the dysregulation of transcriptional and chromatin networks is a crucial component of aging.”

In the paper

“Indeed, allele variants at the FOXO3 locus are associated with extreme longevity (centenarians) in humans (for example, Willcox et al., 2008).”

What the sources say

• Not checked yetcites Willcox et al., 2008 source

In the paper

“Indeed, gene expression has been shown to change drastically during aging (for example, Baumgart et al., 2014; Budovskaya et al., 2008; Zahn et al., 2007).”

What the sources say

• Not checked yetcites Baumgart et al., 2014 source
• Not checked yetcites Budovskaya et al., 2008 source
• Not checked yetcites Zahn et al., 2007 source

In the paper

“Changes in gene regulation (often through expression of a single transcription factor) have been shown to be key for cellular identity.”

What the sources say

• Not checked yetcites Herskowitz, 1989 source
• Not checked yetcites Graf, 2011 source

In the paper

“The activity of FOXO/DAF-16 is positively and negatively regulated by different molecular players (e.g., the insulin/IGF signaling pathway and the nutrient sensor AMPK) and stresses (e.g., oxidative and heat stress) (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

“While it is clear that aging is associated with dysfunction at each layer of the gene regulatory landscape, it is relatively unknown which aspect of gene regulation is the first to become dysregulated during lifespan.”

In the paper

“This interaction is required for the longevity-promoting action of DAF-16 (Riedel et al., 2013).”

What the sources say

• Not checked yetcites Riedel et al., 2013 source

In the paper

“Second, age-associated changes in the activity of transcription factors could promote changes in other epigenomic regulatory layers. This can happen by either altering the expression of chromatin-modifying enzymes and complexes (e.g., histone methyltransferases or nucleosome remodelers) or by the differential recruitment of these enzymes and complexes.”

In the paper

“Meta-analysis of the adult FOXO/DAF-16 transcription regulatory networks in human, mouse, Drosophila, and C. elegans has shown that FOXO/DAF-16 controls the expression of many genes, including those involved in stress response, metabolism, proteostasis, immunity, and neuronal function (Webb et al., 2016).”

What the sources say

• Not checked yetcites Webb et al., 2016 source

In the paper

“Consistent with a role in the progression of aging, the activity of NRF/SKN-1 is dysregulated late in life (Rahman et al., 2013).”

What the sources say

• Not checked yetcites Rahman et al., 2013 source

In the paper

“First, reduced levels of a pro-longevity transcription factor can lead to a loss of stress resistance and cellular protection due to decreased expression of stress-resistance genes.”

In the paper

“Interestingly, the patterning of these marks in the genome changes during aging (Benayoun et al., 2015) (Figure 2).”

What the sources say

• Not checked yetcites Benayoun et al., 2015 source

In the paper

“Furthermore, in C. elegans, DAF-16 recruits the chromatin remodeler SWI/SNF to activate expression of age-related and stress-response genes including heat shock proteins and oxidative stress-response genes (Riedel et al., 2013).”

What the sources say

• Not checked yetcites Riedel et al., 2013 source

In the paper

“Together, these studies identify FOXO/DAF-16 as a key regulatory hub that integrates diverse signals into the control of the chromatin landscape and the expression of genes important for longevity.”

In the paper

“Interestingly, the DNA-binding ability of the NRF/SKN-1 proteins in cultured embryonic stem cells appears to be sensitive to DNA methylation (Domcke et al., 2015).”

What the sources say

• Not checked yetcites Domcke et al., 2015 source

In the paper

“Different enzymes that affect H3K27me3, a repressive histone mark, have opposing effects on lifespan.”

What the sources say

• Not checked yetcites Jin et al., 2011 source
• Not checked yetcites Labbadia and Morimoto, 2015

In the paper

“In response to elevated levels of reactive oxygen species (ROS) and environmental toxins or to nutrient and metabolic changes through mTOR signaling and insulin/IGF signaling, NRF/SKN-1 activates the expression of genes involved in cellular protection (Blackwell et al., 2015; Tebay et al., 2015).”

What the sources say

• Not checked yetcites Blackwell et al., 2015 source
• Not checked yetcites Tebay et al., 2015 source

In the paper

“Thus, changes in the deposition of H3K36me3 appear to play an important role in the regulation of transcription during aging.”

In the paper

“Interestingly, H3K4me3 domains vary in breadth in a locus- and cell-type-specific manner (Benayoun et al., 2014; Chen et al., 2015), and these differences could provide clues about the context-dependent roles of this mark during aging.”

What the sources say

• Not checked yetcites Benayoun et al., 2014 source
• Not checked yetcites Chen et al., 2015 source

In the paper

“Like the H3K27me3 modifiers, knockdown of the H3K4me3 enzymes has been shown to both increase and decrease lifespan, depending on the specific enzyme or context.”

What the sources say

• Not checked yetcites Greer et al., 2010 source
• Not checked yetcites Li et al., 2010
• Not checked yetcites Ni et al., 2012

In the paper

“In addition, cultured senescent human lung fibroblasts have large-scale gains and losses of H3K27me3 compared to early-passage, proliferating cells (Shah et al., 2013).”

What the sources say

• Not checked yetcites Shah et al., 2013 source

In the paper

“H3K4me3-modifying enzymes have also been shown to have long-lasting, transgenerational effects on C. elegans lifespan (Greer et al., 2011, 2016).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Greer et al., 2011, 2016

In the paper

“Interestingly, age-associated changes in global H3K27me3 levels are also context dependent.”

What the sources say

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

In the paper

“Together, these studies suggest that, like H3K27me3-modifying enzymes, H3K4me3-modifying enzymes can both promote and inhibit longevity, likely depending on environmental context and specific loci.”

In the paper

“Consistent with the idea that loss of H3K4me3 is beneficial to longevity, knockdown of the H3K4me3 demethylase KDM5B/RBR-2 in C. elegans hermaphrodites and Drosophila males shortens lifespan (Greer et al., 2010; Li et al., 2010).”

What the sources say

• Not checked yetcites Greer et al., 2010 source
• Not checked yetcites Li et al., 2010

In the paper

“In yeast, loss of H3K36 trimethylation (a mark of transcription elongation) is correlated with a shorter lifespan (Sen et al., 2015).”

What the sources say

• Not checked yetcites Sen et al., 2015 source

In the paper

“In C. elegans, knockdown of the H3K4 methyltransferase SETD1A/SET-2 increases lifespan (Greer et al., 2010).”

What the sources say

• Not checked yetcites Greer et al., 2010 source

In the paper

“Thus, changes in the activity of chromatin modifiers (including Polycomb repressive complex) may occur first during aging and be followed by DNA methylation changes.”

In the paper

“DNA damage appears to be a contributor to heterochromatin loss (Oberdoerffer and Sinclair, 2007) and is discussed in the next section of the review.”

What the sources say

• Not checked yetcites Oberdoerffer and Sinclair, 2007 source

In the paper

“Interestingly, with increased age, there is a loss of H19 lncRNA-mediated repression of the Igf2 locus in mice (Fu et al., 2008).”

What the sources say

• Not checked yetcites Fu et al., 2008

In the paper

“Surprisingly, several genome-wide studies have not found a correlation between age-dependent differential DNA methylation and altered gene expression (Beerman et al., 2013; Yuan et al., 2015).”

What the sources say

• Not checked yetcites Beerman et al., 2013 source
• Not checked yetcites Yuan et al., 2015 source

In the paper

“For example, age-associated DNA hypermethylation of some transcription factor binding sites (Avrahami et al., 2015; Sun et al., 2014; Yuan et al., 2015) suggests that the ability of these proteins to bind DNA and regulate transcription could be disrupted.”

What the sources say

• Not checked yetcites Avrahami et al., 2015 source
• Not checked yetcites Sun et al., 2014 source
• Not checked yetcites Yuan et al., 2015 source

In the paper

“This suggests that an altered chromatin state at specific loci (the histone genes) may precede the reduction of nucleosome occupancy during aging.”

In the paper

“Interestingly, studies in stem cells have also demonstrated that loci with age-associated DNA hypermethylation are enriched for genes normally repressed by Polycomb repressive complex, the complex that methylates H3K27 (Beerman et al., 2013; Sun et al., 2014; Teschendorff et al., 2010).”

What the sources say

• Not checked yetcites Beerman et al., 2013 source
• Not checked yetcites Sun et al., 2014 source
• Not checked yetcites Teschendorff et al., 2010 source

In the paper

“Quiescence is key to maintaining this stem cell population, and the loss of H19-mediated repression of Igf2 leads to hematopoietic stem cell exhaustion (Venkatraman et al., 2013).”

What the sources say

• Not checked yetcites Venkatraman et al., 2013 source

In the paper

“These data suggest the exciting possibility that changes driven by lncRNAs could play an important role in the progression of aging.”

In the paper

“Furthermore, H19-mediated repression of Igf2 has been demonstrated to be important for the maintenance of hematopoietic stem cell quiescence (Venkatraman et al., 2013).”

What the sources say

• Not checked yetcites Venkatraman et al., 2013 source

In the paper

“Thus, there is a link between defects in the nuclear lamin, loss of heterochromatin, and aging.”

In the paper

“FOXA2 is a pioneer transcription factor (Zaret and Carroll, 2011), and therefore, the age-dependent increase in FOXA2 binding likely causes the eviction of nucleosomes from these regions.”

What the sources say

• Not checked yetcites Zaret and Carroll, 2011 source

In the paper

“This lncRNA interacts with MBD1 (a methyl-CpG-binding domain protein) to repress the expression of several genes, including a gene likely to have implications for aging—Igf2, which encodes an insulin-like growth factor (Monnier et al., 2013).”

What the sources say

• Not checked yetcites Monnier et al., 2013 source

In the paper

“the chromatin at transposable elements (Alu, L1, and SVA) becomes more open (De Cecco et al., 2013).”

What the sources say

• Not checked yetcites De Cecco et al., 2013 source

In the paper

“In human cells, loss of SIRT6, an H3K9 deacetylase that silences telomeres, causes telomere dysfunction and premature cellular senescence (Michishita et al., 2008).”

What the sources say

• Not checked yetcites Michishita et al., 2008 source

In the paper

“Reduced DNA methylation (hypomethylation) in mice increases the risk of aneuploidy and cancer (Gaudet et al., 2003)”

What the sources say

• Not checked yetcites Gaudet et al., 2003 source

In the paper

“DNA methylation and heterochromatin help to maintain transposons in an inactive state (Slotkin and Martienssen, 2007).”

What the sources say

• Not checked yetcites Slotkin and Martienssen, 2007

In the paper

“For example, 5-methyl cytosine is inherently more mutagenic than its non-methylated counterpart because if it is deaminated, the base excision repair machinery replaces the nucleotide with a thymine, resulting in a C-to-T mutation (Schmutte et al., 1995).”

What the sources say

• Not checked yetcites Schmutte et al., 1995

In the paper

“These data suggest that altered chromatin states during aging may precede and cause age-associated telomere dysfunction.”

In the paper

“Together, these studies suggest that age-associated epigenomic changes may trigger transposon activation during aging.”

In the paper

“Thus, epigenomic changes and telomere dysfunction may feedback and reinforce each other during aging.”

In the paper

“Communication between mitochondria and the nuclear regulatory genome plays an important role in the progression of aging.”

In the paper

“Furthermore, increasing the level of Sir2 in yeast increases lifespan (Kaeberlein et al., 1999).”

What the sources say

• Not checked yetcites Kaeberlein et al., 1999 source

In the paper

“patients with progeria diseases have an abnormally high rate of chromosome rearrangements and abnormalities (Vijg and Suh, 2013).”

What the sources say

• Not checked yetcites Vijg and Suh, 2013

In the paper

“suggesting that the observed age-associated DNA hypomethylation could contribute to chromosome instability with age.”

In the paper

“age-associated transposon activation could be triggered by epigenomic changes during aging.”

In the paper

“in Drosophila, this may be directly linked to age-dependent memory decline and mortality (Li et al., 2013).”

What the sources say

• Not checked yetcites Li et al., 2013

In the paper

“With age, the expression of transposons increases”

What the sources say

• Not checked yetcites Li et al., 2013

In the paper

“In several species, there is an age-associated accumulation of mutations at varying frequencies depending on the species and rearing conditions (reviewed by Vijg and Suh, 2013).”

What the sources say

• Not checked yetcites Vijg and Suh, 2013

In the paper

“Aneuploidies and large-scale chromosomal rearrangements have an increased incidence with age (reviewed by Vijg and Suh, 2013).”

What the sources say

• Not checked yetcites Vijg and Suh, 2013

In the paper

“the expression of these repetitive DNA elements also increases in senescent cells (De Cecco et al., 2013).”

What the sources say

• Not checked yetcites De Cecco et al., 2013 source

In the paper

“This global repression of chromatin is important to allow the specific upregulation of mitochondrial stress-response genes and lifespan extension (Tian et al., 2016).”

What the sources say

• Not checked yetcites Tian et al., 2016 source

In the paper

“In worms, lifespan extension through knockdown of an electron transport chain component is dependent on a complex mitochondria-responsive transcription regulatory program that includes the ROS-sensitive transcription factors NRF2/SKN-1 and p53/CEP-1 (Chang et al., 2015).”

What the sources say

• Not checked yetcites Chang et al., 2015 source

In the paper

“Induction of the UPRER results in many transcriptional changes through the activation of the transcription regulators XBP1, NFκB, and ATF4 (Taylor, 2016).”

What the sources say

• Not checked yetcites Taylor, 2016 source

In the paper

“an increase in the amount of the repressive histone mark H3K27me3 at specific stress-response genes in C. elegans has been shown to lead to a loss of stress resistance and proteostasis (Labbadia and Morimoto, 2015).”

What the sources say

• Not checked yetcites Labbadia and Morimoto, 2015

In the paper

“changes in H3K4me2/3 deposition with age (Sun et al., 2014; Wood et al., 2010) may alter the ability of the H3K4me2/3 demethylase KDM5/RBR-2 to activate the transcription of key mitochondrial genes (Liu and Secombe, 2015).”

What the sources say

• Not checked yetcites Sun et al., 2014 source
• Not checked yetcites Wood et al., 2010 source
• Not checked yetcites Liu and Secombe, 2015

In the paper

“changes in the methylation of H3K9 and H3K27 have recently been found to be important for the induction of genes involved in the UPRmt in C. elegans, mice, and human cells (Merkwirth et al., 2016; Tian et al., 2016).”

What the sources say

• Not checked yetcites Merkwirth et al., 2016 source
• Not checked yetcites Tian et al., 2016 source

In the paper

“nuclear-mitochondrial communication is also a key determinant of longevity in animals (Chang et al., 2015; Gomes et al., 2013).”

What the sources say

• Not checked yetcites Chang et al., 2015 source
• Not checked yetcites Gomes et al., 2013 source

In the paper

“Once present in the nucleus, ATFS-1 regulates the expression of many genes, including genes important for proteostasis, detoxification, and metabolism (reviewed by Schulz and Haynes, 2015).”

What the sources say

• Not checked yetcites Schulz and Haynes, 2015

In the paper

“ROS signals from the mitochondria can also impact chromatin-mediated silencing in yeast (Schroeder et al., 2013).”

What the sources say

• Not checked yetcites Schroeder et al., 2013 source

In the paper

“dysregulation of FOXO/DAF-16 with age can disrupt proteostasis.”

In the paper

“In aged mice, loss of SIRT1 activity (via a decline in NAD+ levels) leads to increased activity of the HIF-1α transcription factor that is linked with age-associated mitochondrial dysfunction and changes in oxidative phosphorylation (Gomes et al., 2013).”

What the sources say

• Not checked yetcites Gomes et al., 2013 source

In the paper

“In mammals, the transcription factor CHOP mediates the UPRmt gene expression changes in response to unfolded proteins in the mitochondria (Schulz and Haynes, 2015)”

What the sources say

• Not checked yetcites Schulz and Haynes, 2015

In the paper

“the FOXO/DAF-16 transcription factor controls the expression of many genes important for maintenance of a healthy proteome (Webb et al., 2016)”

What the sources say

• Not checked yetcites Webb et al., 2016 source

In the paper

“Together, these studies show that changes in the efficiency or activity of mitochondria with age can result in epigenomic changes that alter lifespan.”

In the paper

“Together, these studies and others support the idea that communication between nuclear gene regulatory mechanisms and mitochondria contributes to the progression of aging.”

In the paper

“in C. elegans, mitochondrial dysfunction results in increased H3K9 methylation and global compaction of chromatin.”

What the sources say

• Not checked yetcites Tian et al., 2016 source

In the paper

“changes in the activity of the transcription activator PGC-1α with age contribute to the loss of mitochondrial biogenesis and function (Rera et al., 2011; Sun et al., 2016).”

What the sources say

• Not checked yetcites Rera et al., 2011 source
• Not checked yetcites Sun et al., 2016 source

In the paper

“In invertebrates and mammals, the transcription factor HSF1 activates expression of protein-folding chaperones in response to elevated levels of unfolded proteins (Labbadia and Morimoto, 2014; Mahat et al., 2016).”

What the sources say

• Not checked yetcites Labbadia and Morimoto, 2014 source
• Not checked yetcites Mahat et al., 2016 source

In the paper

“Thus, changes in the expression of histone-modifying enzymes and the downstream effect on chromatin state and gene expression can shape the ability of cells and animals to withstand stress early during aging (Labbadia and Morimoto, 2015).”

What the sources say

• Not checked yetcites Labbadia and Morimoto, 2015

In the paper

“In C. elegans, the UPRmt is activated primarily by a change in the subcellular localization (from the mitochondria to the nucleus) of the transcription factor ATFS-1.”

What the sources say

• Not checked yetcites Schulz and Haynes, 2015

In the paper

“Together, these studies provide strong evidence that links epigenomic changes with senescence.”

In the paper

“loss of REST activity during early Alzheimer’s disease was associated with a global gain of the activating mark H3K9ac (Lu et al., 2014)”

What the sources say

• Not checked yetcites Lu et al., 2014

In the paper

“nutrient sensing, mitochondria, and epigenomic regulation are interconnected (Berger and Sassone-Corsi, 2015)”

What the sources say

• Not checked yetcites Berger and Sassone-Corsi, 2015

In the paper

“suggesting a potential link between changes in REST, chromatin state, and proteostasis.”

In the paper

“Changes in nutrient sensing and signaling are important hallmarks of aging (López-Otín et al., 2013).”

What the sources say

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

In the paper

“this chromatin-based induction of senescence occurred independently of other mechanisms of inducing senescence, including DNA damage and activation of the CDK inhibition pathway (p53/p21/p16) (Prieur et al., 2011).”

What the sources say

• Not checked yetcites Prieur et al., 2011 source

In the paper

“These studies strongly support a role for senescent cells in the progression of aging.”

In the paper

“these links are likely to be important for the progression of aging.”

In the paper

“The cAMP-responsive element-binding protein (CREB) interacts with many co-activators (cAMP-regulated transcriptional co-activators, or CRTCs) to alter gene expression in response to fasting and feeding signals (Altarejos and Montminy, 2011).”

What the sources say

• Not checked yetcites Altarejos and Montminy, 2011

In the paper

“too much p53 activity, for example, from constitutive activation, is also detrimental to longevity (reviewed by Rufini et al., 2013).”

What the sources say

• Not checked yetcites Rufini et al., 2013 source

In the paper

“knockdown of CRTC-1 in C. elegans extends lifespan (Burkewitz et al., 2015).”

What the sources say

• Not checked yetcites Burkewitz et al., 2015 source

In the paper

“senescence-associated heterochromatin foci are comprised of genomic regions distinct from lamin-associated genomic regions that experience a loss of heterochromatin in progeroid models (Rai and Adams, 2012; Zhang et al., 2015b).”

What the sources say

• Not checked yetcites Rai and Adams, 2012
• Not checked yetcites Zhang et al., 2015b

In the paper

“sirtuins can regulate gene expression by deacetylating histone and non-histone substrates, and this activity depends on a cofactor linked to the cellular energy status, NAD+ (nicotinamide adenine dinucleotide) (Houtkooper et al., 2012).”

What the sources say

• Not checked yetcites Houtkooper et al., 2012 source

In the paper

“the reliance of sirtuins on NAD+ can also be taken advantage of to slow or reverse aging using dietary changes or increased exercise (Guarente, 2013).”

What the sources say

• Not checked yetcites Guarente, 2013 source

In the paper

“Stem cell exhaustion and a decline in stem cell function can result from the induction of senescence as well as from altered epigenomic regulation (Beerman and Rossi, 2015).”

What the sources say

• Not checked yetcites Beerman and Rossi, 2015

In the paper

“AMPK-mediated phosphorylation can also repress transcription factors (and their transcriptional target genes) that are detrimental to lifespan, such as the transcriptional co-activator CRTC (Mair et al., 2011).”

What the sources say

• Not checked yetcites Mair et al., 2011 source

In the paper

“AMPK, a pro-longevity protein kinase, is activated by low cellular energy (Burkewitz et al., 2014).”

What the sources say

• Not checked yetcites Burkewitz et al., 2014 source

In the paper

“Senescence can be triggered by several factors, including DNA damage and telomere dysfunction (Rai and Adams, 2012; Rodier and Campisi, 2011)”

What the sources say

• Not checked yetcites Rai and Adams, 2012
• Not checked yetcites Rodier and Campisi, 2011 source

In the paper

“NAD+ levels are sensitive to diet and exercise (Cantó et al., 2015)”

What the sources say

• Not checked yetcites Cantó et al., 2015 source

In the paper

“AMPK-mediated phosphorylation can promote longevity and gene expression changes, in part by modulating the pro-longevity transcription factor FOXO/DAF-16 (Greer et al., 2007).”

What the sources say

• Not checked yetcites Greer et al., 2007 source

In the paper

“p53 also promotes senescence in response to DNA damage and telomere attrition (Rufini et al., 2013).”

What the sources say

• Not checked yetcites Rufini et al., 2013 source

In the paper

“Senescence is also associated with heterochromatin gains in the form of H3K9me2/3-enriched senescence-associated heterochromatin foci (Rai and Adams, 2012).”

What the sources say

• Not checked yetcites Rai and Adams, 2012

In the paper

“These examples suggest that changes in metabolism and cellular energy availability can trigger changes in transcription factor activity and gene expression during aging.”

In the paper

“The pro-inflammatory transcription factors NF-κB, STAT1, and STAT3 are mediating many of these changes (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

“Comparisons between individuals from different castes have revealed that they have caste-specific DNA methylation and H3K27ac patterns that are functionally important for their behavior (Simola et al., 2016; Yan et al., 2015).”

What the sources say

• Not checked yetcites Simola et al., 2016 source
• Not checked yetcites Yan et al., 2015 source

In the paper

“NF-κB is regulated by many upstream factors and regulators including cytokines, growth factors, the deacetylases SIRT1 and SIRT6, and the transcription factor FOXO (Kawahara et al., 2009; Salminen et al., 2008).”

What the sources say

• Not checked yetcites Kawahara et al., 2009 source
• Not checked yetcites Salminen et al., 2008 source

In the paper

“Given the interconnectedness of the hallmarks of aging, a therapeutic that directly impacts only one contributor to aging could ameliorate other hallmarks of aging.”

In the paper

“Thus, epigenomic changes during senescence are important contributors to age-associated increased inflammation.”

In the paper

“Inflammatory pathways and genes are upregulated in older animals, including humans (Tilstra et al., 2011).”

What the sources say

• Not checked yetcites Tilstra et al., 2011

In the paper

“Compared to youthful stem cells, aged stem cell populations have a unique chromatin state and gene expression profile (Beerman et al., 2013; Liu et al., 2013; Sun et al., 2014).”

What the sources say

• Not checked yetcites Beerman et al., 2013 source
• Not checked yetcites Liu et al., 2013 source
• Not checked yetcites Sun et al., 2014 source

In the paper

“The dysregulation of circadian rhythm has recently been identified as a hallmark of aging (Kondratov, 2007; Orozco-Solis and Sassone-Corsi, 2014).”

What the sources say

• Not checked yetcites Kondratov, 2007 source
• Not checked yetcites Orozco-Solis and Sassone-Corsi, 2014

In the paper

“Together, these upstream regulators and increased pro-inflammatory cytokines from senescent cells lead to increased NF-κB activity and gene expression changes with age.”

In the paper

“the dysregulation of circadian gene expression could itself disrupt the epigenome.”

In the paper

“age-dependent epigenomic alterations could result in a disruption of circadian rhythm.”

In the paper

“these epigenomic changes are likely to contribute to the progression of aging by altering the regenerative capacity of an animal (Beerman and Rossi, 2015).”

What the sources say

• Not checked yetcites Beerman and Rossi, 2015

In the paper

“age-associated increased NF-κB activity could alter the chromatin state of an aging cell by directly increasing the expression of a histone-modifying enzyme.”

In the paper

“this phenomenon may involve male-induced changes in chromatin via the H3K27me3 demethylase UTX-1 (Maures et al., 2014).”

What the sources say

• Not checked yetcites Maures et al., 2014 source

In the paper

“Increased numbers of senescent cells with age are an important contributor to the age-associated increase in inflammation because senescent cells secrete a large number of pro-inflammatory proteins (senescence-associated secretory phenotype, or SASP) (Rodier and Campisi, 2011).”

What the sources say

• Not checked yetcites Rodier and Campisi, 2011 source

In the paper

“age-dependent epigenomic changes associated with the induction of senescence may underlie inflammaging.”

In the paper

“the ability of caloric restriction to extend Drosophila lifespan and improve fat metabolism depends on circadian regulation (Katewa et al., 2016).”

What the sources say

• Not checked yetcites Katewa et al., 2016 source

In the paper

“the NAD+-dependent deacetylase SIRT1 may be a molecular link between metabolism, circadian rhythm, and aging (Orozco-Solis and Sassone-Corsi, 2014).”

What the sources say

• Not checked yetcites Orozco-Solis and Sassone-Corsi, 2014

In the paper

“the senescence-triggered appearance of H3K27me3-depleted “canyons” within genic and enhancer regions is associated with upregulation of SASP-related genes (Shah et al., 2013).”

What the sources say

• Not checked yetcites Shah et al., 2013 source

In the paper

“In C. elegans, the presence of males shortens hermaphrodite lifespan (Maures et al., 2014; Shi and Murphy, 2014)”

What the sources say

• Not checked yetcites Maures et al., 2014 source
• Not checked yetcites Shi and Murphy, 2014

In the paper

“Independently of metabolism, chromatin and nucleosome remodeling are important contributors to the control of circadian rhythm (Kim et al., 2014; Tamayo et al., 2015).”

What the sources say

• Not checked yetcites Kim et al., 2014 source
• Not checked yetcites Tamayo et al., 2015 source

In the paper

“Remodelin, a small molecule that inhibits the acetyl-transferase protein NAT10 (Larrieu et al., 2014).”

What the sources say

• Not checked yetcites Larrieu et al., 2014 source

In the paper

“Heterochronic parabiosis (a technique that links the circulatory systems of an old and young animal) can “rejuvenate” several hallmarks of aging in an old mouse (Conboy et al., 2005; Sinha et al., 2014).”

What the sources say

• Not checked yetcites Conboy et al., 2005 source
• Not checked yetcites Sinha et al., 2014 source

In the paper

“If an intervention or therapeutic is able to rejuvenate an organism, it would be able to reverse the appearance of some or all of the hallmarks of aging, even when initiated in an older organism.”

In the paper

“a therapeutic that restores the regulatory landscape could have a far-reaching impact in slowing or reversing the progression of aging (Rando and Chang, 2012).”

What the sources say

• Not checked yetcites Rando and Chang, 2012 source

In the paper

“Several chemical inhibitors of chromatin-modifying enzymes have been recently developed (Helin and Dhanak, 2013).”

What the sources say

• Not checked yetcites Helin and Dhanak, 2013

In the paper

“caloric restriction in yeast involves nucleosome remodeling (Dang et al., 2014).”

What the sources say

• Not checked yetcites Dang et al., 2014 source

In the paper

“induced neurons from old cells retain some age-associated phenotypes (Mertens et al., 2015)”

What the sources say

• Not checked yetcites Mertens et al., 2015 source

In the paper

“suggesting that passage through a fully pluripotent state may be necessary to completely reset the aging clock.”

In the paper

“genetic manipulations that affect chromatin state and chromatin modifiers can increase lifespan (reviewed by Benayoun et al., 2015).”

What the sources say

• Not checked yetcites Benayoun et al., 2015 source

In the paper

“This result may point toward a possible chromatin-based mechanism for the persistence of the pro-longevity effects of dietary changes.”

In the paper

“compounds that affect chromatin-modifying enzymes have recently been used to successfully treat cancer (Helin and Dhanak, 2013).”

What the sources say

• Not checked yetcites Helin and Dhanak, 2013

In the paper

“some changes that occur very early (for example, during development) could affect the course of aging in adults.”

In the paper

“However, it seems likely that this will be the case because not only are changes in gene expression and regulation common throughout evolution, but these changes can also profoundly impact the ability of a cell or organism to withstand stress in a changing environment and throughout an animal’s lifespan.”