bims-senagi Biomed News
on Senescence and aging
Issue of 2022‒05‒22
twenty papers selected by
Maria Grazia Vizioli
Mayo Clinic

  1. Life Sci. 2022 May 16. pii: S0024-3205(22)00344-7. [Epub ahead of print] 120644
      Cellular senescence refers to the permanent arrest of cell cycle caused by intrinsic and/or extrinsic stressors including oncogene activation, irradiation, DNA damage, oxidative stress, and certain cytokines (including senescence associated secretory phenotype). Cellular senescence is an important factor in aging. Accumulation of senescent cells has been implicated in the causation of various age-related organ disorders, tissue dysfunction, and chronic diseases. It is widely accepted that the biological effects triggered by low-dose radiation (LDR) are different from those caused by high-dose radiation. Experimental evidence suggests that LDR may promote growth and development, enhance longevity, induce embryo production, and delay the progression of chronic diseases. The underlying mechanisms of these effects include modulation of immune response, stimulation of hematopoietic system, antioxidative effect, reduced DNA damage and improved ability for DNA damage repair. In this review, we discuss the possible mechanisms by which LDR prevents senescence and aging from the perspectives of inhibiting cellular senescence and promoting the removal of senescent cells. We review a wide broad of evidence about the beneficial impact of LDR in senescence and aging models (including cardiovascular diseases, neurological diseases, arthritis and osteoporosis, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis) to highlight the potential value of LDR in preventing aging and age-related diseases. However, there is no consensus on the effect of LDR on human health, and several important aspects require further investigation.
    Keywords:  Aging; Immune; Low-dose radiation (LDR); Senescence; Senescent cells
  2. Immun Ageing. 2022 May 17. 19(1): 20
      NF-κB is generally recognized as an important regulator of ageing, through its roles in cellular senescence and inflammatory pathways. Activated in virtually all cell-cell communication networks of the immune system, NF-κB is thought to affect age-related defects of both innate and adaptive immune cells, relevant to inflamm-ageing and declining adaptive immunity, respectively. Moreover, the family of NF-κB proteins that exist as heterodimers and homodimers exert their function beyond the immune system. Given their involvement in diverse areas such as DNA damage to metabolism, NF-κB has the potential to serve as linkages between known hallmarks of ageing. However, the complexity of NF-κB dimer composition, dynamic signaling, and tissue-specific actions has received relatively little attention in ageing research. Here, we discuss some areas where further research may bear fruit in our understanding the impact of NF-κB in healthy ageing and longevity.
    Keywords:  Ageing; Immunosenescence; Inflammation; Mammalian stress pathways; NF-κB
  3. Cell Mol Life Sci. 2022 May 18. 79(6): 297
      Aging is the result of the accumulation of a wide variety of molecular and cellular damage over time. This has been associated with a number of features termed hallmarks of aging, including genomic instability, loss of proteostasis, telomere attrition, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and impaired intercellular communication. On the other hand, sirtuins are enzymes with an important role in aging and life extension, of which humans have seven paralogs (SIRT1 to SIRT7). SIRT7 is the least studied sirtuin to date, but it has been reported to serve important functions, such as promoting ribosomal RNA expression, aiding in DNA damage repair, and regulating chromatin compaction. Several studies have established a close relationship between SIRT7 and age-related processes, but knowledge in this area is still scarce. Therefore, the purpose of this review was to analyze how SIRT7 is associated with each of the hallmarks of aging, as well as with some of age-associated diseases, such as cardiovascular diseases, obesity, osteoporosis, and cancer.
    Keywords:  Aging-associated diseases; Hallmarks of aging; Nucleolus; Ribosomal RNA; Sirtuins
  4. Aging (Albany NY). 2022 May 16. 14(undefined):
      Senescence occurs in response to a number of damaging stimuli to limit oncogenic transformation and cancer development. As no single, universal senescence marker has been discovered, the confident classification of senescence induction requires the parallel assessment of a series of hallmarks. Therefore, there is a growing need for "first-pass" tools of senescence identification to streamline experimental workflows and complement conventional markers. Here, we utilise a high content, multidimensional phenotypic profiling-based approach, to assess the morphological profiles of senescent cells induced via a range of stimuli. In the context of senescence, we refer to these as senescence-associated morphological profiles (SAMPs), as they facilitate distinction between senescent and proliferating cells. The complexity of the profiles generated also allows exploration of the heterogeneity both between models of senescence and within an individual senescence model, providing a level of insight at the single cell level. Furthermore, we also demonstrate that these models are applicable to the assessment of senescence in vivo, which remains a key challenge for the field. Therefore, we believe SAMPs has the potential to serve as a useful addition in the repertoire of senescence researchers, either as a first-pass tool or as part of the established senescence hallmarks.
    Keywords:  high content profiling of senescence hallmarks; morphology; senescence; senescence-associated morphological profiles (SAMPs)
  5. Front Physiol. 2022 ;13 864758
      Stress-induced premature senescence can contribute to the accelerated metabolic aging process in diabetes. Progressive accumulation of senescent cells in the brain, especially those displaying the harmful inflammatory senescence-associated secretory phenotype (SASP), may lead to cognitive impairment linked with metabolic disturbances. In this context, the senescence within the neurovascular unit (NVU) should be studied as much as in the neurons as emerging evidence shows that neurogliovascular communication is critical for brain health. It is also known that cerebrovascular dysfunction and decreased cerebral blood flow (CBF) precede the occurrence of neuronal pathologies and overt cognitive impairment. Various studies have shown that endothelial cells, the major component of the NVU, acquire a senescent phenotype via various molecular mediators and pathways upon exposure to high glucose and other conditions mimicking metabolic disturbances. In addition, senescence in the other cells that are part of the NVU, like pericytes and vascular smooth cells, was also triggered upon exposure to diabetic conditions. The senescence within the NVU may compromise functional and trophic coupling among glial, vascular, and neuronal cells and the resulting SASP may contribute to the chronic neurovascular inflammation observed in Alzheimer's Disease and Related Dementias (ADRD). The link between diabetes-mediated cerebral microvascular dysfunction, NVU senescence, inflammation, and cognitive impairment must be widely studied to design therapeutic strategies.
    Keywords:  cerebral vasculature; cognitive impairment; diabetes; senescence; vascular
  6. FASEB J. 2022 Jun;36(6): e22353
      Endothelial cell (EC) aging plays a vital role in the pathogenesis of cardiovascular disease (CVD). MicroRNAs have emerged as crucial regulators of target gene expression by inhibiting mRNA translation and/or promoting mRNA degradation. We identify an aging-related and oxidative stress-responsive microRNA, miR-181b, that inhibits endothelial cell apoptosis and senescence. In gain- or loss-of-function studies, miR-181b regulated the expression of key apoptosis markers (Bcl2, Bax, cleaved-Caspase3) and senescence markers (p16, p21, γH2AX) and the ratio of apoptotic cells (TUNEL-positive) and senescent cells (SA-βgal-positive) in H2 O2 -induced ECs. Mechanistically, miR-181b targets MAP3K3 and modulates a MAP3K3/MKK/MAPK signaling pathway. MAP3K3 knockdown recapitulated the phenotype of miR-181b overexpression and miR-181b was dependent on MAP3K3 for regulating EC apoptosis and senescence. In vivo, miR-181b expression showed a negative correlation with increasing age in the mouse aorta. Endothelial-specific deficiency of miR-181a2b2 increased the target MAP3K3, markers of vascular senescence (p16, p21), and DNA double-strand breaks (γH2AX) in the aorta of aged mice. Collectively, this study unveils an important role of miR-181b in regulating vascular endothelial aging via an MAP3K3-MAPK signaling pathway, providing new potential therapeutic targets for antiaging therapy in CVD.
    Keywords:  apoptosis; atherosclerosis; endothelium; microRNA; senescence
  7. Biol Rev Camb Philos Soc. 2022 May 15.
      Atherosclerosis, characterized by lipid-rich plaques in the arterial wall, is an age-related disorder and a leading cause of mortality worldwide. However, the specific mechanisms remain complex. Recently, emerging evidence has demonstrated that senescence of various types of cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages, endothelial progenitor cells (EPCs), and adipose-derived mesenchymal stem cells (AMSCs) contributes to atherosclerosis. Cellular senescence and atherosclerosis share various causative stimuli, in which dyslipidemia has attracted much attention. Dyslipidemia, mainly referred to elevated plasma levels of atherogenic lipids or lipoproteins, or functional impairment of anti-atherogenic lipids or lipoproteins, plays a pivotal role both in cellular senescence and atherosclerosis. In this review, we summarize the current evidence for dyslipidemia-induced cellular senescence during atherosclerosis, with a focus on low-density lipoprotein (LDL) and its modifications, hydrolysate of triglyceride-rich lipoproteins (TRLs), and high-density lipoprotein (HDL), respectively. Furthermore, we describe the underlying mechanisms linking dyslipidemia-induced cellular senescence and atherosclerosis. Finally, we discuss the senescence-related therapeutic strategies for atherosclerosis, with special attention given to the anti-atherosclerotic effects of promising geroprotectors as well as anti-senescence effects of current lipid-lowering drugs.
    Keywords:  adipose-derived mesenchymal stem cells; atherosclerosis; dyslipidemia; endothelial cells; macrophages; senescence; vascular smooth muscle cells
  8. Pathol Oncol Res. 2022 ;28 1610156
      Replicative senescence is irreversible cell proliferation arrest for somatic cells which can be circumvented in cancers. Cellular senescence is a process, which may play two opposite roles. On the one hand, this is a natural protection of somatic cells against unlimited proliferation and malignant transformation. On the other hand, cellular secretion caused by senescence can stimulate inflammation and proliferation of adjacent cells that may promote malignancy. The main genes controlling the senescence pathways are also well known as tumor suppressors. Almost 140 genes regulate both cellular senescence and cancer pathways. About two thirds of these genes (64%) are regulated by microRNAs. Senescence-associated miRNAs can stimulate cancer progression or act as tumor suppressors. Here we review the role playing by senescence-associated miRNAs in development, diagnostics and treatment of pancreatic cancer.
    Keywords:  cellular senescence; oncogene; pancreatic ductal adenocarcinoma; senescence bypass; senescence-associated miRNA; tumor suppressor
  9. Geroscience. 2022 May 20.
      Cognitive function progressively declines with advancing age. The aging process can be promoted by obesity and attenuated by exercise. Both conditions affect levels of the chemokine CX3CL1 in peripheral tissues; however, its role in cognitive aging is unknown. In the current study, we administered CX3CL1 into the peritoneal cavity of aged mice to investigate its impact on the aging process. In the peritoneal cavity, CX3CL1 not only reversed the age-associated accumulation of cells expressing the senescence marker p16INK4a but also increased peritoneal phagocytic activity, indicating that CX3CL1 affected the phenotypes of peritoneal cells. In the hippocampus of aged mice, intraperitoneal administration of CX3CL1 increased the number of Type-2 neural stem cells and promoted brain-derived neurotrophic factor (BDNF) expression. This treatment, furthermore, improved novel object recognition memory impaired with advancing age. Intraperitoneal transplantation of peritoneal cells from CX3CL1-treated aged mice improved novel object recognition memory in recipient aged mice. It indicates that peritoneal cells have a critical role in the CX3CL1-induced improvement of recognition memory in aged mice. Vagotomy inhibited the CX3CL1-induced increase in BDNF expression, demonstrating that the vagus nerve is involved in the hippocampal BDNF expression induced by intraperitoneal administration of CX3CL1. Thus, our results demonstrate that a novel connection among the peritoneal cells, the vagus nerve, and the hippocampus can reverse the age-associated decline in recognition memory.
    Keywords:  BDNF; Novel object recognition; Peritoneal cells; Rejuvenation
  10. Rejuvenation Res. 2022 May 18.
      We aimed to investigate the association of circulatory senescence-associated secretory phenotypes (SASP) produced by senescent cells with chronological and menopausal age in women aged 45 years or more. The proteomic profiles for 32 SASP factors of plasma samples were measured in 76 healthy postmenopausal women aged 46-82 years from the Korean Genome and Epidemiology Study Cardiovascular Disease Association Study (KoGES-CAVAS). We assessed the association between the SASP factors and aging indicators (chronological age, menopausal age, and years since menopause) using single- and multi-protein models. First, we composed a profile of proteins associated with chronological age, menopausal age, and years since menopause. In a single-protein model, three proteins (growth differentiation factor 15 (GDF15), insulin-like growth factor binding protein-2 (IGFBP-2), and tumor necrosis factor-α (TNF-α)) are positively associated with chronological age. Menopausal age and years since menopause are interrelated with Interlukin-8 (IL-8). The direction of association between menopausal age and monocyte chemoattractant protein-1 (MCP-1) was only negative, and IGFBP-2 and TNF-α were significant in all three aging factors. We also constructed parsimonious multi-protein models to confirm the association of the proteomic signature for aging after adjusting for covariates and the combination of proteomic signature of 13 proteins (GDF15, IFN-γ, IGFBP-2, IGFBP-7, IL-15, IL-1β, IL-17A, IL-8, MCP-1, TIMP-2, TNF-α, VEGF-A, and IP-10) appear to be associated with chronological age and menopausal state of individuals. Thus, by observing association between the selected SASPs and age-related markers among healthy postmenopausal women, we examine how menopause in women relates to proteomic indicators of aging and highlight the potential use of SASP factors as a marker to reflect the state of biological aging attributed by ovarian senescence.
  11. Cell Biosci. 2022 May 14. 12(1): 62
      BACKGROUND: Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined.RESULTS: In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence.
    CONCLUSIONS: Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.
    Keywords:  Glycolysis; MSCs; Metabolism; RNA sequence; Senescence
  12. Aging Cell. 2022 May 15. e13629
      A sustained state of methionine restriction (MR) dramatically extends the healthspan of several model organisms. For example, continuously methionine-restricted rodents have less age-related pathology and are up to 45% longer-lived than controls. Promisingly, MR is feasible for humans, and studies have suggested that methionine-restricted individuals may receive similar benefits to rodents. However, long-term adherence to a methionine-restricted diet is likely to be challenging for many individuals. Prompted by this, and the fact that intermittent variants of other healthspan-extending interventions (i.e., intermittent fasting and the cyclic ketogenic diet) are just as effective, if not more, than their continuous counterparts, we hypothesized that an intermittent form of MR might produce similar healthspan benefits to continuous MR. Accordingly, we developed two increasingly stringent forms of intermittent MR (IMR) and assessed whether mice maintained on these diets demonstrate the beneficial metabolic changes typically observed for continuous MR. To the best of our knowledge, we show for the first time that IMR produces similar beneficial metabolic effects to continuous MR, including improved glucose homeostasis and protection against diet-induced obesity and hepatosteatosis. In addition, like continuous MR, IMR confers beneficial changes in the plasma levels of the hormones IGF-1, FGF-21, leptin, and adiponectin. Together, our findings demonstrate that the more practicable intermittent form of MR produces similar healthspan benefits to continuous MR, and thus may represent a more appealing alternative to the classical intervention.
    Keywords:  IGF-1; aging; intermittent; lifespan; longevity; metabolism; mice; obesity
  13. Am J Physiol Cell Physiol. 2022 May 18.
      Ovarian cancer is a highly aggressive disease with poor survival rates in part due to diagnosis after dissemination throughout the peritoneal cavity. It is well-known that inflammatory signals affect ovarian cancer dissemination. Inflammation is a hallmark of cellular senescence, a stable cell cycle arrest induced by a variety of stimuli including many of the therapies used to treat ovarian cancer patients. Indeed, recent work has illustrated that ovarian cancer cells in vitro, mouse models, and patient tumors undergo senescence in response to platinum-based or poly(ADP-ribose) polymerase (PARP) inhibitor therapies, standard-of-care therapies for ovarian cancer. This inflammatory response, termed the senescence-associated secretory phenotype (SASP), is highly dynamic and has pleotropic roles that can be both beneficial and detrimental in cell-intrinsic and cell-extrinsic ways. Recent data in other cancer types suggest that the SASP promotes metastasis. Here, we outline what is known about the SASP in ovarian cancer and discuss both how the SASP may promote ovarian cancer dissemination and strategies to mitigate effects of the SASP.
    Keywords:  metastasis; microenvironment; ovarian cancer; senescence; therapy
  14. Stem Cell Res Ther. 2022 May 16. 13(1): 201
      As global aging accelerates, the prevention and treatment of age-related bone diseases are becoming a critical issue. In the process of senescence, bone marrow mesenchymal stem cells (BMSCs) gradually lose the capability of self-renewal and functional differentiation, resulting in impairment of bone tissue regeneration and disorder of bone tissue homeostasis. Alteration in epigenetic modification is an essential factor of BMSC dysfunction during aging. Its transferability and reversibility provide the possibility to combat BMSC aging by reversing age-related modifications. Emerging evidence demonstrates that epigenetic therapy based on aberrant epigenetic modifications could alleviate the senescence and dysfunction of stem cells. This review summarizes potential therapeutic targets for BMSC aging, introduces some potential approaches to alleviating BMSC aging, and analyzes its prospect in the clinical application of age-related bone diseases.
    Keywords:  Age-related bone diseases; Aging; Epigenetics; Mesenchymal stem cell (MSC); Therapy
  15. Prog Neuropsychopharmacol Biol Psychiatry. 2022 May 16. pii: S0278-5846(22)00068-9. [Epub ahead of print] 110576
      Immunosenescence is a term used to describe the age-related changes in the immune system. Immunosenescence is associated with complex alterations and dysregulation of immune function and inflammatory processes. Age-related changes in innate immune responses including alterations in chemotactic, phagocytic, and natural killing functions, impaired antigen presenting capacity, and dysregulated inflammatory response have been described. The most striking and best characterized feature of immunosenescence is the decline in both number and function of T cells. With age there is decreased proliferation, decreased number of antigen-naïve T cells, and increased number of antigen-experienced memory T cells. This decline in naïve T cell population is associated with impaired immunity and reduced response to new or mutated pathogens. While the absolute number of peripheral B cells appears constant with age, changes in B cell functions including reduced antibody production and response and cell memory have been described. However, the main alteration in cell-mediated function that has been reported across all species with aging is those observed in in T cell. These T cell mediated changes have been shown to contribute to increased susceptibility to infection and cancer in older adults. In addition to functional and phenotype alterations in immune cells, studies demonstrate that circulating concentrations of inflammatory mediators in older adults are higher than those of young. This low grade, chronic inflammatory state that occurs in the context of aging has been termed "inflammaging". This review will focus on age-related changes in the immune system including immunosenescence and inflammation as well as the functional consequences of these age-related alterations for the aged.
    Keywords:  Aging; Immune function; Infection; Inflammation; Neurodegenerative diseases
  16. Aging Cell. 2022 May 15. e13628
      Age-related memory impairment (AMI) is a common phenomenon across species. Vulnerability to interfering stimuli has been proposed to be an important cause of AMI. However, the molecular mechanisms underlying this vulnerability-related AMI remain unknown. Here we show that learning-activated MAPK signals are gradually lost with age, leading to vulnerability-related AMI in Drosophila. Young flies (2- or 3-day-old) exhibited a significant increase in phosphorylated MAPK levels within 15 min after learning, whereas aged flies (25-day-old) did not. Compared to 3-day-old flies, significant 1 h memory impairments were observed in 15-, 20-, and 30-day-old flies, but not in 10-day-old flies. However, with post-learning interfering stimuli such as cooling or electric stimuli, 10-day-old flies had worse memory performance at 1 h than 3-day-old flies, showing a premature AMI phenomenon. Increasing learning-activated MAPK signals through acute transgene expression in mushroom body (MB) neurons restored physiological trace of 1 h memory in a pair of MB output neurons in aged flies. Decreasing such signals in young flies mimicked the impairment of 1 h memory trace in aged flies. Restoring learning-activated MAPK signals in MB neurons in aged flies significantly suppressed AMI even with interfering stimuli. Thus, our data suggest that age-related loss of learning-activated neuronal MAPK signals causes memory vulnerability to interfering stimuli, thereby leading to AMI.
    Keywords:   Drosophila ; MAPK; aging; interference; memory; protection; vulnerability
  17. Front Cell Dev Biol. 2022 ;10 862675
      Renal fibrosis is a common feature of various chronic kidney diseases (CKD). However, its underlying mechanism has not been totally clarified. C-X-C motif chemokine receptor (CXCR) family plays a role in renal fibrosis, however, detailed mechanisms have not been elucidated. Here, we report that CXCR2 has a potential role in tubular cell senescence and renal fibrosis, and is associated with β-catenin-activated mitochondrial dysfunction. CXCR2 is one of most increased members among CXCR family in unilateral ureteral obstruction (UUO) mice. CXCR2 was expressed primarily in tubules and co-localized with p16INK4A, a cellular senescence marker, and β-catenin. Administration of SB225002, a selective CXCR2 antagonist, significantly inhibited the activation of β-catenin signaling, restored mitochondrial function, protected against tubular cell senescence and renal fibrosis in unilateral ureteral obstruction (UUO) mice. In unilateral ischemia-reperfusion injury (UIRI) mice, treatment with interlukin-8 (IL-8), the ligand of CXCR2, further aggravated β-catenin activation, mitochondrial dysfunction, tubular cell senescence and renal fibrosis, whereas knockdown of p16INK4A inhibited IL-8-induced these effects. In vitro, SB225002 inhibited mitochondrial dysfunction and tubular cell senescence. Furthermore, ICG-001, a β-catenin signaling blocker, significantly retarded CXCR2-induced cellular senescence and fibrotic changes. These results suggest that CXCR2 promotes tubular cell senescence and renal fibrosis through inducing β-catenin-activated mitochondrial dysfunction.
    Keywords:  CXCR2; mitochondrial dysfunction; renal fibrosis; tubular cell senescence; β-catenin
  18. Nat Commun. 2022 May 19. 13(1): 2782
      Cytoplasmic RNP condensates enriched in mRNAs and proteins are found in various cell types and associated with both buffering and regulatory functions. While a clear link has been established between accumulation of aberrant RNP aggregates and progression of aging-related neurodegenerative diseases, the impact of physiological aging on neuronal RNP condensates has never been explored. Through high-resolution imaging, we uncover that RNP components progressively cluster into large yet dynamic granules in the aging Drosophila brain. We further show that age-dependent clustering is caused by an increase in the stoichiometry of the conserved helicase Me31B/DDX6, and requires PKA kinase activity. Finally, our functional analysis reveals that mRNA species recruited to RNP condensates upon aging exhibit age-dependent translational repression, indicating that co-clustering of selected mRNAs and translation regulators into repressive condensates may contribute to the specific post-transcriptional changes in gene expression observed in the course of aging.
  19. Nat Commun. 2022 May 16. 13(1): 2691
      Hematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here, we present an integrated analysis of transcriptome and chromatin accessibility of aged HSCs and downstream progenitors. Alterations in chromatin accessibility preferentially take place in HSCs with aging, which gradually resolve with differentiation. Differentially open accessible regions (open DARs) in aged HSCs are enriched for enhancers and show enrichment of binding motifs of the STAT, ATF, and CNC family transcription factors that are activated in response to external stresses. Genes linked to open DARs show significantly higher levels of basal expression and their expression reaches significantly higher peaks after cytokine stimulation in aged HSCs than in young HSCs, suggesting that open DARs contribute to augmented transcriptional responses under stress conditions. However, a short-term stress challenge that mimics infection is not sufficient to induce persistent chromatin accessibility changes in young HSCs. These results indicate that the ongoing and/or history of exposure to external stresses may be epigenetically inscribed in HSCs to augment their responses to external stimuli.
  20. Proc Natl Acad Sci U S A. 2022 May 24. 119(21): e2120887119
      SignificanceEpigenetic estimators of age (known as clocks) allow one to identify interventions that slow or reverse aging. Previous epigenetic clocks only applied to one species at a time. Here, we describe epigenetic clocks that apply to both dogs and humans. These clocks, which measure methylation levels in highly conserved stretches of the DNA, promise to increase the likelihood that interventions that reverse epigenetic age in one species will have the same effect in the other.
    Keywords:  Canis familiaris; aging; dog; epigenetic clock; methylation