bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023–07–16
eightteen papers selected by
Ayesh Seneviratne, Western University
  1. Klotho, a longevity factor, improves cognitive function in aging nonhuman primates.
  2. New Insight into the Causes, Consequences and Correction of Hematopoietic Stem Cell Ageing.
  3. NAD metabolism: Role in senescence regulation and aging.
  4. Role of Estrogen Receptor α in Aging and Chronic Disease.
  5. Decrypting biological hallmarks of aging in people with HIV.
  6. Senolytic and senomorphic interventions to defy senescence-associated mitochondrial dysfunction.
  7. Inflammatory biomarkers of frailty: A review.
  8. Mitochondria in cell senescence: A Friend or Foe?
  9. The role of mitochondria and mitophagy in cell senescence.
  10. Clones of aging: When better fitness can be dangerous.
  11. Targeting epigenetics: A novel promise for Alzheimer's disease treatment.
  12. Capturing copper to inhibit inflammation.
  13. CD34 Protein: Its expression and function in inflammation.
  14. Mitochondria-derived peptides in healthy ageing and therapy of age-related diseases.
  15. Preparation of physiologically active inside-out vesicles from plant inner mitochondrial membranes.
  16. Chromatin accessibility dynamics of neurogenic niche cells reveal defects in neural stem cell adhesion and migration during aging.
  17. STING is a cell-intrinsic metabolic checkpoint restricting aerobic glycolysis by targeting HK2.
  18. Chemically induced reprogramming to reverse cellular aging.
  1. Nat Aging. 2023 Jul 10.
    Klotho, a longevity factor, improves cognitive function in aging nonhuman primates.
      
    DOI:  https://doi.org/10.1038/s43587-023-00466-2
  2. Exp Hematol. 2023 Jul 09. pii: S0301-472X(23)01614-4. [Epub ahead of print]
    New Insight into the Causes, Consequences and Correction of Hematopoietic Stem Cell Ageing.
    Els Mansell, Dawn S Lin, Stephen J Loughran, Michael D Milsom, Jennifer J Trowbridge.
      Ageing of hematopoietic stem cells (HSCs) is characterised by lineage bias, increased clonal expansion and functional decrease. At the molecular level, aged HSCs typically display metabolic dysregulation, upregulation of inflammatory pathways and downregulation of DNA repair pathways. Cellular ageing of HSCs, driven by cell-intrinsic and cell-extrinsic factors, causes predisposition to anaemia, adaptive immune compromise, myelodysplasia and malignancy. In fact, most hematological diseases are strongly associated with age. But what is the biological foundation for decreased fitness with age? And are there therapeutic windows to resolve age-related hematopoietic decline? These questions were the focus of the International Society for Experimental Hematology New Investigator Committee Fall 2022 Webinar. This review touches on the latest insights from two leading laboratories into inflammatory- and niche- driven stem cell ageing and includes speculation on strategies to prevent or correct age-related decline in HSC function (see Fig 1).
    DOI:  https://doi.org/10.1016/j.exphem.2023.07.002
  3. Aging Cell. 2023 Jul 09. e13920
    NAD metabolism: Role in senescence regulation and aging.
    Claudia Christiano Silva Chini, Heidi Soares Cordeiro, Ngan Le Kim Tran, Eduardo Nunes Chini.
      The geroscience hypothesis proposes that addressing the biology of aging could directly prevent the onset or mitigate the severity of multiple chronic diseases. Understanding the interplay between key aspects of the biological hallmarks of aging is essential in delivering the promises of the geroscience hypothesis. Notably, the nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several biological hallmarks of aging, including cellular senescence, and changes in NAD metabolism have been shown to be involved in the aging process. The relationship between NAD metabolism and cellular senescence appears to be complex. On the one hand, the accumulation of DNA damage and mitochondrial dysfunction induced by low NAD+ can promote the development of senescence. On the other hand, the low NAD+ state that occurs during aging may inhibit SASP development as this secretory phenotype and the development of cellular senescence are both highly metabolically demanding. However, to date, the impact of NAD+ metabolism on the progression of the cellular senescence phenotype has not been fully characterized. Therefore, to explore the implications of NAD metabolism and NAD replacement therapies, it is essential to consider their interactions with other hallmarks of aging, including cellular senescence. We propose that a comprehensive understanding of the interplay between NAD boosting strategies and senolytic agents is necessary to advance the field.
    Keywords:  NAD+ metabolism; SASP; aging; nicotinamide adenine dinucleotide; senescence
    DOI:  https://doi.org/10.1111/acel.13920
  4. Adv Geriatr Med Res. 2023 ;pii: e230005. [Epub ahead of print]5(2):
    Role of Estrogen Receptor α in Aging and Chronic Disease.
    José V V Isola, Sunghwan Ko, Sarah R Ocañas, Michael B Stout.
      Estrogen receptor alpha (ERα) plays a crucial role in reproductive function in both sexes. It also mediates cellular responses to estrogens in multiple nonreproductive organ systems, many of which regulate systemic metabolic homeostasis and inflammatory processes in mammals. The loss of estrogens and/or ERα agonism during aging is associated with the emergence of several comorbid conditions, particularly in females undergoing the menopausal transition. Emerging data also suggests that male mammals likely benefit from ERα agonism if done in a way that circumvents feminizing characteristics. This has led us, and others, to speculate that tissue-specific ERα agonism may hold therapeutic potential for curtailing aging and chronic disease burden in males and females that are at high-risk of cancer and/or cardiovascular events with traditional estrogen replacement therapies. In this mini-review, we emphasize the role of ERα in the brain and liver, summarizing recent evidence that indicates these two organs systems mediate the beneficial effects of estrogens on metabolism and inflammation during aging. We also discuss how 17α-estradiol administration elicits health benefits in an ERα-dependent manner, which provides proof-of-concept that ERα may be a druggable target for attenuating aging and age-related disease burden.
    Keywords:  17α-estradiol; HPG axis; hypothalamus; liver; metabolism; neuroinflammation
    DOI:  https://doi.org/10.20900/agmr20230005
  5. Curr Opin HIV AIDS. 2023 Jul 07.
    Decrypting biological hallmarks of aging in people with HIV.
    Thomas A Premeaux, Lishomwa C Ndhlovu.
       PURPOSE OF REVIEW: HIV infection adds further complexity to the heterogenous process of aging. In this focused review, we examine and discuss recent advances to better elucidate mechanisms of biological aging perturbed and accelerated in the context of HIV, particularly among those with viral suppression through the benefits of antiretroviral therapy (ART). New hypotheses from these studies are poised to provide an improved understanding of multifaceted pathways that converge and likely form the basis for effective interventions toward successful aging.
    RECENT FINDINGS: Evidence to date suggests multiple mechanisms of biological aging impact people living with HIV (PLWH). Recent literature delves and expands on how epigenetic alterations, telomere attrition, mitochondrial perturbations, and intercellular communications may underpin accelerated or accentuated aging phenotypes and the disproportionate prevalence of age-related complications among PLWH. Although most hallmarks of aging are likely exacerbated in the setting of HIV, ongoing research efforts are providing new insight on the collective impact these conserved pathways may have in the aging disease processes.
    SUMMARY: New knowledge on underlying molecular disease mechanisms impacting people aging with HIV are reviewed. Also examined are studies that may facilitate the development and implementation of effective therapeutics and guidance on improving geriatric HIV clinical care.
    DOI:  https://doi.org/10.1097/COH.0000000000000810
  6. Adv Protein Chem Struct Biol. 2023 ;pii: S1876-1623(23)00041-X. [Epub ahead of print]136 217-247
    Senolytic and senomorphic interventions to defy senescence-associated mitochondrial dysfunction.
    Jan O Nehlin.
      The accumulation of senescent cells in the aging individual is associated with an increase in the occurrence of age-associated pathologies that contribute to poor health, frailty, and mortality. The number and type of senescent cells is viewed as a contributor to the body's senescence burden. Cellular models of senescence are based on induction of senescence in cultured cells in the laboratory. One type of senescence is triggered by mitochondrial dysfunction. There are several indications that mitochondria defects contribute to body aging. Senotherapeutics, targeting senescent cells, have been shown to induce their lysis by means of senolytics, or repress expression of their secretome, by means of senomorphics, senostatics or gerosuppressors. An outline of the mechanism of action of various senotherapeutics targeting mitochondria and senescence-associated mitochondria dysfunction will be here addressed. The combination of geroprotective interventions together with senotherapeutics will help to strengthen mitochondrial energy metabolism, biogenesis and turnover, and lengthen the mitochondria healthspan, minimizing one of several molecular pathways contributing to the aging phenotype.
    Keywords:  Aging; Gerosuppressors; Mitochondria; Senescence; Senolytics; Senomorphics; Senotherapeutics
    DOI:  https://doi.org/10.1016/bs.apcsb.2023.02.020
  7. Exp Gerontol. 2023 Jul 08. pii: S0531-5565(23)00174-2. [Epub ahead of print] 112253
    Inflammatory biomarkers of frailty: A review.
    Liying Zhang, Xiaofeng Zeng, Fuqian He, Xiaoli Huang.
      Frailty is a common geriatric syndrome characterized by increased vulnerability and is associated with adverse clinical events such as falls, hospitalization, and death. Early diagnosis and early intervention can delay or reverse frailty and ensure the healthy aging of older individuals. At present, there are no gold standard biomarkers for the diagnosis of frailty, which mainly relies on the scale to assess frailty, and the scale has shortcomings such as lagging assessment, subjectivity, and poor consistency. Frailty biomarkers help in early diagnosis and intervention in frailty. The purpose of this review is to summarize the existing inflammatory markers of frailty and focus on novel inflammatory biomarkers of frailty that can be used to help identify frailty early and explore potential intervention targets.
    Keywords:  Biomarkers; Frailty; Geriatric syndrome; Inflammaging; Inflammation
    DOI:  https://doi.org/10.1016/j.exger.2023.112253
  8. Adv Protein Chem Struct Biol. 2023 ;pii: S1876-1623(23)00040-8. [Epub ahead of print]136 35-91
    Mitochondria in cell senescence: A Friend or Foe?
    Qian Chen, Lindon Young, Robert Barsotti.
      Cell senescence denotes cell growth arrest in response to continuous replication or stresses damaging DNA or mitochondria. Mounting research suggests that cell senescence attributes to aging-associated failing organ function and diseases. Conversely, it participates in embryonic tissue maturation, wound healing, tissue regeneration, and tumor suppression. The acute or chronic properties and microenvironment may explain the double faces of senescence. Senescent cells display unique characteristics. In particular, its mitochondria become elongated with altered metabolomes and dynamics. Accordingly, mitochondria reform their function to produce more reactive oxygen species at the cost of low ATP production. Meanwhile, destructed mitochondrial unfolded protein responses further break the delicate proteostasis fostering mitochondrial dysfunction. Additionally, the release of mitochondrial damage-associated molecular patterns, mitochondrial Ca2+ overload, and altered NAD+ level intertwine other cellular organelle strengthening senescence. These findings further intrigue researchers to develop anti-senescence interventions. Applying mitochondrial-targeted antioxidants reduces cell senescence and mitigates aging by restoring mitochondrial function and attenuating oxidative stress. Metformin and caloric restriction also manifest senescent rescuing effects by increasing mitochondria efficiency and alleviating oxidative damage. On the other hand, Bcl2 family protein inhibitors eradicate senescent cells by inducing apoptosis to facilitate cancer chemotherapy. This review describes the different aspects of mitochondrial changes in senescence and highlights the recent progress of some anti-senescence strategies.
    Keywords:  Bcl2 family protein inhibitors; Caloric restriction; Cell senescence; Metabolic reprograming; Metformin; Mitochondria-targeted antioxidants; Mitochondrial damage-associated molecular patterns; Mitochondrial unfolded protein responses; NAD(+); Reactive oxygen species
    DOI:  https://doi.org/10.1016/bs.apcsb.2023.02.019
  9. Adv Protein Chem Struct Biol. 2023 ;pii: S1876-1623(23)00043-3. [Epub ahead of print]136 93-115
    The role of mitochondria and mitophagy in cell senescence.
    Tayyab Ali, Fatma Hussain, Haroon Ur Rashid Kayani, Muhammad Naeem, Fozia Anjum.
      Mitochondrial malfunction and cell senescence have been defined as the hallmarks of aging. Cell senescence leads to the loss of health allied with aging. While deciphering the complex association between mitochondria and cellular senescence, it is observed that senescence has a two-faced nature being beneficial and hazardous. This duality of cellular senescence is associated with circumstantial aspects. During the process of cellular senescence, dysfunctional mitochondria are accumulated, the efficiency of the oxidative phosphorylation process declines along with the enhanced synthesis of reactive oxygen species. It is suggested that reduction in the negative consequences of senescence throughout old age might be accomplished by targeting the mitochondria as all roads lead towards mitochondria. It is unclear how perturbation of mitophagy in senescence results in the accumulation of mitochondria, impairment of mitochondrial biogenesis and onset of diseases. Understanding this complex interplay will bring about a long yet healthy lifespan. But definitely casual and specific players contribute in the initiation and conservation of the cell senescence. Variations in metabolism, quality control and dynamics of mitochondria are observed during cell aging process. Several On-target and Off-target mechanisms can also cause side effects in cellular senescence. Translational research of these mechanisms may lead to effective clinical interventions. This chapter reviews the role of mitochondria, homeostatic mechanisms and mitophagy as drivers and effectors of cell senescence along with multiple signalling pathways that lead to the initiation, maintenance, induction and suppression of cellular aging process during health and disease.
    Keywords:  Autophagy; Cell senescence; Mitophagy; Signaling pathways
    DOI:  https://doi.org/10.1016/bs.apcsb.2023.03.001
  10. Eur J Cell Biol. 2023 Jul 06. pii: S0171-9335(23)00055-9. [Epub ahead of print]102(3): 151340
    Clones of aging: When better fitness can be dangerous.
    Fabio Marongiu, Samuele Cheri, Ezio Laconi.
      The biological and clinical significance of aberrant clonal expansions in aged tissues is being intensely discussed. Evidence is accruing that these clones often result from the normal dynamics of cell turnover in our tissues. The aged tissue microenvironment is prone to favour the emergence of specific clones with higher fitness partly because of an overall decline in cell intrinsic regenerative potential of surrounding counterparts. Thus, expanding clones in aged tissues need not to be mechanistically associated with the development of cancer, albeit this is a possibility. We suggest that growth pattern is a critical phenotypic attribute that impacts on the fate of such clonal proliferations. The acquisition of a better proliferative fitness, coupled with a defect in tissue pattern formation, could represent a dangerous mix setting the stage for their evolution towards neoplasia.
    Keywords:  Aging; Cancer; Clonal expansions; Clones; Growth pattern
    DOI:  https://doi.org/10.1016/j.ejcb.2023.151340
  11. Ageing Res Rev. 2023 Jul 07. pii: S1568-1637(23)00162-9. [Epub ahead of print]90 102003
    Targeting epigenetics: A novel promise for Alzheimer's disease treatment.
    Danko Jeremic, Lydia Jiménez-Díaz, Juan D Navarro-López.
      So far, the search for a cure for Alzheimer Disease (AD) has been unsuccessful. The only approved drugs attenuate some symptoms, but do not halt the progress of this disease, which affects 50 million people worldwide and will increase its incidence in the coming decades. Such scenario demands new therapeutic approaches to fight against this devastating dementia. In recent years, multi-omics research and the analysis of differential epigenetic marks in AD subjects have contributed to our understanding of AD; however, the impact of epigenetic research is yet to be seen. This review integrates the most recent data on pathological processes and epigenetic changes relevant for aging and AD, as well as current therapies targeting epigenetic machinery in clinical trials. Evidence shows that epigenetic modifications play a key role in gene expression, which could provide multi-target preventative and therapeutic approaches in AD. Both novel and repurposed drugs are employed in AD clinical trials due to their epigenetic effects, as well as increasing number of natural compounds. Given the reversible nature of epigenetic modifications and the complexity of gene-environment interactions, the combination of epigenetic-based therapies with environmental strategies and drugs with multiple targets might be needed to properly help AD patients.
    Keywords:  Aging; Alzheimer’s; Clinical trials; Epigenetics; Mild cognitive impairment
    DOI:  https://doi.org/10.1016/j.arr.2023.102003
  12. Nat Chem Biol. 2023 Jul 13.
    Capturing copper to inhibit inflammation.
    Christopher J Chang, Donita C Brady.
      
    DOI:  https://doi.org/10.1038/s41589-023-01383-6
  13. Cell Tissue Res. 2023 Jul 14.
    CD34 Protein: Its expression and function in inflammation.
    Carolina Rego Rodrigues, Sahib Moga, Baljit Singh, Gurpreet Kaur Aulakh.
      CD34 has spear-headed the field of basic research and clinical transplantation since the first reports of its expression on hematopoietic stem cells (HSCs). Expressed in mice, humans, rats and other species, CD34 has been used for more than 40 years as a hematopoietic stem and progenitor cell marker. It was later found that muscle satellite cells and epidermal precursors can also be identified with the aid of CD34. Despite the usefulness of CD34 as a marker of HSCs, its overall purpose in animal physiology has remained unclear. This review recaptures CD34 structure, evolutionary conservation, proposed functions, and role in lung inflammation, to describe current research findings and to provide guidance for future studies on CD34.
    Keywords:  CD34; Inflammation; LPS; Lung injury; Stem cells
    DOI:  https://doi.org/10.1007/s00441-023-03811-4
  14. Adv Protein Chem Struct Biol. 2023 ;pii: S1876-1623(23)00036-6. [Epub ahead of print]136 197-215
    Mitochondria-derived peptides in healthy ageing and therapy of age-related diseases.
    Siarhei A Dabravolski.
      Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by mitochondrial DNA and involved in various stress-protecting mechanisms. To date, eight mitochondrial-derived peptides have been identified: MOTS-c sequence is hidden in the 12 S rRNA gene (MT-RNR1), and the other 7 (humanin and small humanin-like peptides 1-6) are encoded by the 16 S rRNA (MT-RNR2) gene. While the anti-apoptotic, anti-inflammatory and cardioprotective activities of MDPs are well described, recent research suggests that MDPs are sensitive metabolic sensors, closely connected with mtDNA mutation-associated diseases and age-associated metabolic disorders. In this chapter, we focus on the recent progress in understanding the metabolo-protective properties of MDPs, their role in maintenance of the cellular and mitochondrial homeostasis associated with age-related diseases: Alzheimer's disease, cognitive decline, macular degeneration and cataracts. Also, we will discuss MDPs-based and MDPs-targeted interventions to treat age-related diseases and extend a healthy lifespan.
    Keywords:  Age-related macular degeneration; Ageing; Alzheimer’s disease; Healthspan; Humanin; Lifespan; MOTS-c; Mitochondria-derived peptides; SHLPs
    DOI:  https://doi.org/10.1016/bs.apcsb.2023.02.015
  15. Front Plant Sci. 2023 ;14 1216227
    Preparation of physiologically active inside-out vesicles from plant inner mitochondrial membranes.
    Leander Ehmke, Gerd Hause, Ralf Bernd Klösgen, Bationa Bennewitz.
      For many metabolites, the major barrier between cytosol and mitochondrial matrix is the inner membrane of mitochondria, the site of the respiratory electron transport chain. In consequence, it houses numerous transporters which facilitate the controlled exchange of metabolites, ions, and even proteins between these cellular compartments. While their import into the organelle can be studied with isolated mitochondria or mitoplasts, the analysis of their export from the matrix into the intermembrane space or even the cytosol demands for more sophisticated approaches. Among those, inside-out inner membrane vesicles are particularly useful, since they allow the direct presentation of the potential export substrates to the membrane without prior import into the organelle. Here we present a protocol for the isolation of such inside-out vesicles of the inner membrane of plant mitochondria based on repeated freeze/thaw-cycles of freshly prepared mitoplasts. Electron microscopy and Western analysis could show that the majority of the vesicles have single envelope membranes in an inside-out topology. The vesicles are furthermore physiologically active, as demonstrated by assays measuring the enzymatic activities of Complex I (NADH dehydrogenase), Complex V (ATP synthase) and the mitochondrial processing peptidase (MPP) associated with Complex III. Hence, the method presented here provides a good basis for further studies of the inner mitochondrial membrane and mitochondrial export processes.
    Keywords:  Pisum sativum; electron microscopy; enzymatic activity; inside-out IMM vesicles; plant mitochondria
    DOI:  https://doi.org/10.3389/fpls.2023.1216227
  16. Nat Aging. 2023 Jul 13.
    Chromatin accessibility dynamics of neurogenic niche cells reveal defects in neural stem cell adhesion and migration during aging.
    Robin W Yeo, Olivia Y Zhou, Brian L Zhong, Eric D Sun, Paloma Navarro Negredo, Surag Nair, Mahfuza Sharmin, Tyson J Ruetz, Mikaela Wilson, Anshul Kundaje, Alexander R Dunn, Anne Brunet.
      The regenerative potential of brain stem cell niches deteriorates during aging. Yet the mechanisms underlying this decline are largely unknown. Here we characterize genome-wide chromatin accessibility of neurogenic niche cells in vivo during aging. Interestingly, chromatin accessibility at adhesion and migration genes decreases with age in quiescent neural stem cells (NSCs) but increases with age in activated (proliferative) NSCs. Quiescent and activated NSCs exhibit opposing adhesion behaviors during aging: quiescent NSCs become less adhesive, whereas activated NSCs become more adhesive. Old activated NSCs also show decreased migration in vitro and diminished mobilization out of the niche for neurogenesis in vivo. Using tension sensors, we find that aging increases force-producing adhesions in activated NSCs. Inhibiting the cytoskeletal-regulating kinase ROCK reduces these adhesions, restores migration in old activated NSCs in vitro, and boosts neurogenesis in vivo. These results have implications for restoring the migratory potential of NSCs and for improving neurogenesis in the aged brain.
    DOI:  https://doi.org/10.1038/s43587-023-00449-3
  17. Nat Cell Biol. 2023 Jul 13.
    STING is a cell-intrinsic metabolic checkpoint restricting aerobic glycolysis by targeting HK2.
    Liting Zhang, Congqing Jiang, Yunhong Zhong, Kongliang Sun, Huiru Jing, Jiayu Song, Jun Xie, Yaru Zhou, Mao Tian, Chuchu Zhang, Xiaona Sun, Shaowei Wang, Xi Cheng, Yuelan Zhang, Wei Wei, Xiang Li, Bishi Fu, Pinghui Feng, Bing Wu, Hong-Bing Shu, Junjie Zhang.
      Evasion of antitumour immunity is a hallmark of cancer. STING, a putative innate immune signalling adaptor, has a pivotal role in mounting antitumour immunity by coordinating innate sensing and adaptive immune surveillance in myeloid cells. STING is markedly silenced in various human malignancies and acts as a cell-intrinsic tumour suppressor. How STING exerts intrinsic antitumour activity remains unclear. Here, we report that STING restricts aerobic glycolysis independent of its innate immune function. Mechanistically, STING targets hexokinase II (HK2) to block its hexokinase activity. As such, STING inhibits HK2 to restrict tumour aerobic glycolysis and promote antitumour immunity in vivo. In human colorectal carcinoma samples, lactate, which can be used as a surrogate for aerobic glycolysis, is negatively correlated with STING expression level and antitumour immunity. Taken together, this study reveals that STING functions as a cell-intrinsic metabolic checkpoint that restricts aerobic glycolysis to promote antitumour immunity. These findings have important implications for the development of STING-based therapeutic modalities to improve antitumour immunotherapy.
    DOI:  https://doi.org/10.1038/s41556-023-01185-x
  18. Aging (Albany NY). 2023 Jul 12. 15
    Chemically induced reprogramming to reverse cellular aging.
    Jae-Hyun Yang, Christopher A Petty, Thomas Dixon-McDougall, Maria Vina Lopez, Alexander Tyshkovskiy, Sun Maybury-Lewis, Xiao Tian, Nabilah Ibrahim, Zhili Chen, Patrick T Griffin, Matthew Arnold, Jien Li, Oswaldo A Martinez, Alexander Behn, Ryan Rogers-Hammond, Suzanne Angeli, Vadim N Gladyshev, David A Sinclair.
      A hallmark of eukaryotic aging is a loss of epigenetic information, a process that can be reversed. We have previously shown that the ectopic induction of the Yamanaka factors OCT4, SOX2, and KLF4 (OSK) in mammals can restore youthful DNA methylation patterns, transcript profiles, and tissue function, without erasing cellular identity, a process that requires active DNA demethylation. To screen for molecules that reverse cellular aging and rejuvenate human cells without altering the genome, we developed high-throughput cell-based assays that distinguish young from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic compartmentalization (NCC) assay. We identify six chemical cocktails, which, in less than a week and without compromising cellular identity, restore a youthful genome-wide transcript profile and reverse transcriptomic age. Thus, rejuvenation by age reversal can be achieved, not only by genetic, but also chemical means.
    Keywords:  epigenetics; information theory of aging; rejuvenation medicine; reprogramming; small molecules
    DOI:  https://doi.org/10.18632/aging.204896
This page is being maintained by Thomas Krichel. It was last updated on 2024‒11‒22 at 4:22.