Dataset Preview

Split (1)

train

The full dataset viewer is not available (click to read why). Only showing a preview of the rows.

[{'expected': SplitInfo(name='train', num_bytes=0, num_examples=0, shard_lengths=None, dataset_name=None), 'recorded': SplitInfo(name='train', num_bytes=3168107, num_examples=2933, shard_lengths=None, dataset_name='longevity_rag_chunks')}]

Error code:   UnexpectedError

Need help to make the dataset viewer work? Make sure to review how to configure the dataset viewer, and open a discussion for direct support.

section string	content string	source string	topic string	year float64
Summary of the Hallmarks of Aging	Aging is driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them. We propose the following twelve hallmarks o...	Cell	Hallmarks of Aging	2,022
Genomic Instability and DNA Damage Sources	Genome integrity and stability are pervasively threatened by exogenous chemical, physical, and biological agents, as well as by endogenous challenges such as DNA replication errors, chromosome segregation defects, oxidative processes, and spontaneous hydrolytic reactions. The wide range of genetic lesions caused by the...	Cell	Genomic Instability	2,022
DNA Repair Networks and Age-Related Decline	Accordingly, organisms have evolved a complex array of DNA repair and maintenance mechanisms to deal with the damage inflicted to nuclear and mitochondrial DNA (mtDNA) and to ensure the appropriate chromosomal architecture and stability. These DNA repair networks lose efficiency with age, which accentuates the accumula...	Cell	Genomic Instability	2,022
Somatic Mutations and Genomic Alterations in Aging	Cells from aged humans and model organisms accumulate somatic mutations at nuclear DNA. Other forms of damage, such as chromosomal aneuploidy and copy-number variations, are also associated with aging. All these DNA alterations may affect essential genes and transcriptional pathways, resulting in dysfunctional cells th...	Cell	Genomic Instability	2,022
Mutation Rates, DNA Repair, and Longevity Correlation	These data also suggest that similar to carcinogenesis, driver mutations alone may not be sufficient to accelerate aging because they require a permissive microenvironment created by non-mutagenic promoting factors to become penetrant. Comparative analysis of the mutational landscape across mammalian species has shown ...	Cell	Genomic Instability	2,022
SIRT6 and DNA Repair Enhancement	Sirtuin-6 (SIRT6) may play a major role in this differential reparative efficiency across species. Overexpression of SIRT6 in mice reduces genomic instability, improves double-strand break repair, and extends lifespan, although other explanations, such as improved glucose metabolism and restoration of energy homeostasi...	Cell	Genomic Instability	2,022
Mitochondrial DNA Instability and Aging	Genomic instability affecting mtDNA may contribute to aging and age-related pathologies. mtDNA is strongly impacted by aging-associated mutations and deletions due to its high replicative index, the limited efficiency of its repair mechanisms, its oxidative microenvironment, and the lack of protective histones embracin...	Cell	Mitochondrial DNA	2,022
Sources and Implications of mtDNA Mutations	Of note, ultra-sensitive sequencing indicates that most mtDNA mutations in aged cells arise from replication errors caused by mtDNA polymerase γ rather than from oxidative stress. Preliminary evidence that mtDNA mutations might be directly involved in aging and age-related pathologies was provided by human disorders th...	Cell	Mitochondrial DNA	2,022
Nuclear Architecture and Genome Stability	Defects in the nuclear lamina, which constitutes a scaffold for tethering chromatin and protein complexes, can generate genome instability. Accelerated aging syndromes such as the Hutchinson-Gilford and the Néstor-Guillermo progeria syndromes (HGPS and NGPS, respectively) are caused by mutations in genes LMNA and BANF1...	Cell	Nuclear Architecture	2,022
Therapeutic Approaches for Progeria and Nuclear Lamina Defects	The causal implication of nuclear lamina abnormalities in premature aging has been corroborated by the observation that decreasing prelamin A or progerin levels delays the onset of progeroid features and extends lifespan in mouse models of HGPS. This can be achieved by systemic injection of antisense oligonucleotides, ...	Cell	Nuclear Architecture	2,022
Mechanisms and Consequences of Telomere Attrition	DNA damage at the end of chromosomes (telomeres) contributes to aging and age-linked diseases. Replicative DNA polymerases are unable to complete the copy of telomere regions of eukaryotic DNA. Accordingly, after several rounds of cell division, telomeres undergo a substantial shortening that induces genomic instabilit...	Cell	Telomere Attrition	2,022
Telomerase Deficiency and Age-Related Diseases	Telomerase deficiency in humans is associated with premature development of diseases such as pulmonary fibrosis, aplastic anemia, and dyskeratosis congenita, all of which hamper the regenerative capacity of the affected tissues. Telomere shortening is also observed during normal aging in many different species, includi...	Cell	Telomere Attrition	2,022
Experimental Evidence and Telomerase Reactivation	Genetically modified animal models have revealed causal links between telomere attrition, cellular senescence, and organismal aging. Mice with shortened or lengthened telomeres exhibit decreased or increased lifespan, respectively. Notably, the premature aging of telomerase-deficient mice can be reverted when telomeras...	Cell	Telomere Attrition	2,022
Telomerase Activation and Therapeutic Potential	In humans, many studies have provided evidence for causal associations between short telomere length and age-related diseases. In particular, generation of mouse models with short telomeres has demonstrated that telomeric attrition is at the origin of telomere syndromes and prevalent age-associated diseases, such as pu...	Cell	Telomere Attrition	2,022
Epigenetic Alterations and Their Role in Aging	The large variety of epigenetic changes that contribute to aging include alterations in DNA methylation patterns, abnormal post-translational modification of histones, aberrant chromatin remodeling, and deregulated function of non-coding RNAs (ncRNAs). These regulatory and often reversible changes impact on gene expres...	Cell	Epigenetic Alterations	2,022
Age-Related Changes in DNA Methylation	The human DNA methylation landscape accumulates multiple changes with the passage of time. Early studies described an age-associated global hypomethylation, but further analyses revealed that specific loci, including those of several tumor suppressor genes and Polycomb target genes, are hypermethylated with age. Cells ...	Cell	DNA Methylation	2,022
Epigenetic Clocks and Longevity Interventions	Epigenetic clocks based on DNA methylation status at selected sites have been introduced to predict chronological age and mortality risk as well as to evaluate interventions that may extend human lifespan. This has been demonstrated with protocols aimed at thymus regeneration, which resulted in improved risk indices fo...	Cell	DNA Methylation	2,022
Histone Modifications and Aging	Global loss of histones and tissue-dependent changes in their post-translational modifications are also closely linked to aging. Increased histone expression extends lifespan in Drosophila, whereas increased histone H4K16 acetylation or H3K4 trimethylation and decreased levels of H3K9 or H3K27 trimethylation are found ...	Cell	Histone Modifications	2,022
Histone-Modifying Enzymes and Longevity Regulation	Histone demethylases modulate lifespan by targeting components of key longevity routes such as the insulin/insulin growth factor-1 (IGF-1) signaling pathway. Other histone-modifying enzymes such as members of the SIRT family of protein deacetylases and ADP-ribosyltransferases also contribute to healthy aging. Transgeni...	Cell	Histone Modifications	2,022
Therapeutic Modulation of Histone Modifiers	Together, these findings are consistent with the idea that a decrease in deacetylase activity would result in chromatin relaxation, increased exposure to DNA damaging agents, and enhanced genomic instability. Conversely, genetic inactivation of the histone acetyltransferase KAT7 in human stem cells decreases histone H3...	Cell	Histone Modifications	2,022
Chromatin Remodeling and Epigenetic Regulation in Aging	Besides DNA- and histone-modifiers, several chromosomal proteins and chromatin remodeling factors, such as the heterochromatin protein 1a (HP1a) and Polycomb group proteins which are implicated in genomic stability and DNA repair, may modulate aging. Alterations in these epigenetic factors result in profound changes in...	Cell	Chromatin Remodeling	2,022
Heterochromatin Maintenance and Longevity	The causal relevance of these chromatin alterations in aging has been largely studied in invertebrates in which loss-of-function mutations in HP1a decrease longevity, whereas its overexpression expands healthspan and lifespan. Similar studies in mammals are still limited, but most studies indicate that heterochromatin ...	Cell	Chromatin Remodeling	2,022
Non-Coding RNAs and Their Role in Aging	The large and growing universe of ncRNAs, including lncRNAs (such as telomeric RNAs or TERRA), microRNAs (miRNAs), and circular RNAs, has emerged as epigenetic factors with ability to influence aging. ncRNAs modulate healthspan and lifespan by post-transcriptional targeting of components of longevity networks or by reg...	Cell	Non-Coding RNAs	2,022
MicroRNAs as Modulators of Longevity	Gain- and loss-of-function studies first confirmed the capacity of several miRNAs to modulate longevity in invertebrates. Subsequent studies in mice have provided causal evidence on the functional relevance of miRNAs in aging. For example, miRNA-188-3p expression is upregulated in skeletal endothelium during aging and ...	Cell	Non-Coding RNAs	2,022
Retrotransposon Derepression and Aging Mechanisms	Recent studies have unveiled the role of retrotransposons in aging of complex metazoans, including humans. These retrotransposable elements are mobile genetic units that can move from one genomic location to another, using a molecular mechanism that involves an RNA intermediate. Retrotransposons consist of long intersp...	Cell	Retrotransposons	2,022
Therapeutic Targeting of Retrotransposons for Longevity	Treatments with nucleoside reverse-transcriptase inhibitors (NRTIs), which suppress or attenuate retrotransposition, extend lifespan of Sirt6-null mice and improve healthspan, ameliorating bone and muscle phenotypes. Likewise, treatment of aged wild-type mice with NRTIs reduces the levels of DNA damage markers. Moreove...	Cell	Retrotransposons	2,022
Gene Expression Changes During Aging	The mechanisms underlying the effects of all the above epigenetic factors converge at the modulation of gene expression levels. Aging causes an increase of the transcriptional noise and an aberrant production and maturation of many mRNAs. Microarray-based comparisons of young and old tissues from human and other specie...	Cell	Gene Expression	2,022
Transcriptomic Shifts and Therapeutic Implications	Single-cell transcriptomic and plasma proteomics of multiple cell types and organs at several ages across the entire mouse lifespan have unveiled remarkable gene expression shifts during aging. These changes specially affect certain biological processes, such as inflammation, protein folding, extracellular matrix (ECM)...	Cell	Gene Expression	2,022
Loss of Proteostasis and Age-Related Diseases	Aging and several age-related morbidities, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and cataract, are associated with impaired protein homeostasis or proteostasis, leading to the accumulation of misfolded, oxidized, glycated, or ubiquitinylated proteins that often form aggr...	Cell	Loss of Proteostasis	2,022
Proteostasis Collapse and Translation Accuracy	Intracellular proteostasis can be disrupted due to the enhanced production of erroneously translated, misfolded, or incomplete proteins. Genetic manipulation of the ribosomal protein RPS23 to improve the accuracy of RNA-to-protein translation extends lifespan in Schizosaccharomyces pombe, Caenorhabditis elegans, and Dr...	Cell	Loss of Proteostasis	2,022
Quality Control Failure and Proteasome Decline	The proteostasis network also collapses when mechanisms assuring quality control fail, for instance, due to reduced function of the unfolded protein response (UPR) in the endoplasmic reticulum (ER), when stabilization of correctly folded proteins is compromised, or when mechanisms for the degradation of proteins by the...	Cell	Loss of Proteostasis	2,022
Lysosomal Degradation and Autophagy in Proteostasis	The degradation of proteins by the lysosome can be achieved in a specific fashion, through chaperone-mediated autophagy (CMA), wherein proteins exposing a pentapeptide motif resembling KFERQ first bind to heat shock protein HSC70 and then to lysosome-associated membrane protein type 2A (LAMP2A), which facilitates the t...	Cell	Loss of Proteostasis	2,022
Proteostasis Disruption and Accelerated Aging	Perturbation of general proteostasis accelerates aging. For example, feeding Drosophila melanogaster with advanced glycation end products (AGEs) or lipofuscin (an aggregate of covalently cross-linked proteins, sugars, and lipids) causes the accumulation of AGE-modified and carbonylated proteins with a reduction of heal...	Cell	Loss of Proteostasis	2,022
Experimental Restoration of Proteostasis and Longevity	Experimental amelioration of proteostasis can retard the aging process. Intranasal application of recombinant human HSP70 protein to mice enhances proteasome activity, reduces brain lipofuscin levels, enhances cognitive functions, and extends lifespan. Similarly, administration of the chemical chaperone 4-phenylbutyrat...	Cell	Loss of Proteostasis	2,022
Integrated Stress Response and Longevity Mechanisms	A phase 3 clinical trial has revealed that in patients with recent ALS diagnosis, administration of the antihypertensive guanabenz inhibits progression to the life-threatening bulbar stage. Guanabenz may act to stimulate the phosphorylation (or to inhibit the dephosphorylation) of eukaryotic translation initiation fact...	Cell	Loss of Proteostasis	2,022
Disabled Macroautophagy and Aging	Macroautophagy (that we will refer to as 'autophagy') involves the sequestration of cytoplasmic material in two-membrane vesicles, the autophagosomes, which later fuse with lysosomes for the digestion of luminal content. Thus, autophagy is not only involved in proteostasis but also affects non-proteinaceous macromolecu...	Cell	Disabled Macroautophagy	2,022
Autophagy Decline and Its Impact on Aging	In humans, the expression of autophagy-related genes, such as ATG5, ATG7, and BECN1, declines with age. CD4+ T lymphocytes isolated from the offspring of parents with exceptional longevity show enhanced autophagic activity compared with age-matched controls. Decreased autophagy in circulating B and T lymphocytes from a...	Cell	Disabled Macroautophagy	2,022
Genetic Inhibition of Autophagy and Premature Aging	Genetic inhibition of autophagy accelerates the aging process in model organisms. This process is partially reversible, as illustrated in mice in which Atg5 is downregulated by a doxycycline-inducible shRNA. Atg5 knockdown causes the premature degeneration and senescence of multiple organ systems leading to premature d...	Cell	Disabled Macroautophagy	2,022
Autophagy Activation and Lifespan Extension	There is ample evidence that stimulation of autophagic flux increases healthspan and lifespan in model organisms. For example, increasing autophagy solely in the enterocytes of the intestine increases Drosophila lifespan. In mice, transgenic overexpression of Atg5 under the control of a ubiquitously expressed promoter ...	Cell	Disabled Macroautophagy	2,022
Spermidine and EP300-Linked Autophagy Enhancement	Oral supplementation of spermidine to mice induces autophagy in multiple organs and extends longevity by up to 25%, accompanied by reduced cardiac aging. This effect is lost upon cardiomyocyte-specific knockout of Atg7, suggesting that it relies on autophagy. Mechanistically, the pro-autophagic effects of spermidine ha...	Cell	Disabled Macroautophagy	2,022
Autophagy-Linked Metabolic and Therapeutic Pathways	Deoxyhypusine synthase deficiency in murine T cells triggers severe intestinal inflammation coupled to epigenetic remodeling and rewiring of the tricarboxylic acid cycle, whereas spermidine treatment of wild-type mice protects against colitis and colon carcinogenesis. Hence, both EP300 inhibition and eIF5A hypusination...	Cell	Disabled Macroautophagy	2,022
Nutrient-Sensing Networks and Aging	The nutrient-sensing network is highly conserved in evolution. It includes extracellular ligands, such as insulins and IGFs, the receptor tyrosine kinases with which they interact, as well as intracellular signaling cascades. These cascades involve the PI3K-AKT and the Ras-MEK-ERK pathways, as well as transcription fac...	Cell	Deregulated Nutrient-Sensing	2,022
Somatotrophic Axis and Longevity Regulation	In youth, activity of this signaling network functions to promote beneficial anabolic processes, but during adulthood, it acquires pro-aging properties. The somatotrophic axis—the first one historically implicated in the control of aging—is a growth-stimulatory cascade that, at its apex, involves growth hormone (GH) pr...	Cell	Deregulated Nutrient-Sensing	2,022
ALK Pathway and Metabolic Aging	Another signaling pathway involved in nutrient-sensing relies on the receptor tyrosine kinase ALK, which, in mice, is induced in the hypothalamus by feeding and responds to the ligands augmentor α and β (Auga and Augb). In Drosophila, knockdown of ALK decreases triglyceride levels and the expression of several insulin-...	Cell	Deregulated Nutrient-Sensing	2,022
Rapamycin and Nutrient-Sensing Therapeutics	Drugs targeting diseases such as cancer and metabolic disease often engage the nutrient-sensing network, thus such drugs are candidates for repurposing as geroprotectors. Rapamycin and rapalogs, which disrupt the MTORC1 complex, have proved to extend lifespan in model organisms even with treatment starting late in adul...	Cell	Deregulated Nutrient-Sensing	2,022
Nutrient Sensing and Dietary Regulation of Aging	Diet is one of the most practical targets for interventions into human aging. Mechanistically, overnutrition: (1) triggers intracellular nutrient sensors, such as MTORC1 (activated by leucine and other amino acids), and the acetyltransferase EP300 (activated by acetyl coenzyme A); (2) inhibits sensors that detect nutri...	Cell	Deregulated Nutrient-Sensing	2,022
Dietary Restriction and Intermittent Fasting in Longevity	Nutrient sensors constitute targets for potential longevity drugs, but health benefits and extended lifespan might also be achieved by dietary restrictions. Mechanistically, this is possible via reduction of overall caloric intake, manipulation of the dietary composition, or time-restricted feeding. Dietary restriction...	Cell	Deregulated Nutrient-Sensing	2,022
Ketogenic Diet, Fasting, and Metabolic Benefits	Rapamycin-induced longevity extension (which in flies partially depends on autophagy induction) can be obtained by constant long-term exposure, as well as by intermittent regimens, suggesting that pulsatile inhibition of this axis is sufficient to obtain the benefits of lifespan extension. The optimal interval for such...	Cell	Deregulated Nutrient-Sensing	2,022
Mitochondrial Dysfunction and Aging Mechanisms	Mitochondria are not only the powerhouses of the cell but also constitute latent triggers of inflammation when reactive oxygen species (ROS) or mitochondrial DNA (mtDNA) leak out of the organelle, causing activation of inflammasomes or cytosolic DNA sensors, respectively, and cell death when activators of caspases, nuc...	Cell	Mitochondrial Dysfunction	2,022
Healthspan Extension via Mitochondrial Function Enhancement	Healthspan-extending interventions can stimulate the function of mitochondria. For instance, placebo-controlled trials have revealed positive effects of L-carnitine supplementation on both pre-frail subjects and elderly men. The effect is possibly mediated by counteracting age-related declining L-carnitine levels which...	Cell	Mitochondrial Dysfunction	2,022
Mitochondrial Uncoupling and Pharmacological Interventions	Partial uncoupling of hepatic mitochondria by means of a controlled release mitochondrial protonophore (CRMP) also reverses age-related metabolic syndrome in mice with high-fat diet-induced obesity. In non-human primate models including spontaneously obese rhesus macaques and high-fat, high-fructose-fed cynomolgus maca...	Cell	Mitochondrial Dysfunction	2,022
Mitochondrial Membrane Permeability and Therapeutic Strategies	Increased mitochondrial membrane permeability (MMP) due to the absence of serum/glucocorticoid regulated kinase-1 decreases lifespan, which is further compromised when autophagy is enhanced but normalized when autophagy is inhibited by knockdown of essential autophagy-relevant genes in C. elegans. Hence, MMP may consti...	Cell	Mitochondrial Dysfunction	2,022
Mitochondrial Microproteins and Aging	Plasma levels of the microprotein humanin, which is encoded by mtDNA, decline with age. However, centenarians and their offspring exhibit high levels of humanin. Notably, humanin levels negatively correlate with IGF1 in humans and treatment of patients with GH-insufficiency, with GH or IGF1, reduces circulating humanin...	Cell	Mitochondrial Dysfunction	2,022
Overview of Cellular Senescence and Aging	Cellular senescence is a response elicited by acute or chronic damage. In humans, senescent cells accumulate in multiple tissues at different rates, from 2- to 20-fold when comparing young (<35 years) to old (>65 years) healthy donors, mainly affecting fibroblasts, endothelial cells, and immune cells, although all cell...	Cell	Cellular Senescence	2,022
Triggers and Mechanisms of Cellular Senescence	The types of damage that trigger primary senescence include oncogenic signaling, genotoxic damage, critically short telomeres, mitochondrial damage, viral or bacterial infection, oxidative damage, nutrient imbalance, and mechanical stress. In addition, secondary or paracrine senescence can be triggered by extracellular...	Cell	Cellular Senescence	2,022
Biological Roles and Reversibility of Senescence	The net result of these processes is a long-term and viable proliferative arrest with a low rate of spontaneous escape. Depending on their molecular makeup, cancer cells exposed to genotoxic therapy may undergo a canonical senescence response with a highly stable cell cycle arrest, a senescence-like response with a hig...	Cell	Cellular Senescence	2,022
Senescence and Human Diseases	Cellular senescence is implicated in multiple non-proliferative diseases, including lung fibrosis, kidney diseases, liver steatosis, obesity-associated metabolic syndrome, type I and II diabetes, atherosclerosis, as well as Alzheimer’s and Parkinson’s diseases. The pathogenic role of cellular senescence in these diseas...	Cell	Cellular Senescence	2,022
SASP Signaling Pathways and Consequences	SASP is highly heterogeneous, depending on the cell type-specific activation of innate immunity signaling pathways (cGAS/STING, TLRs, and NLRPs), mTORC1, and transcription factors (NF-κB, CBPs, GATA4, and others). SASP usually has simultaneous and partially conflicting consequences on the microenvironment: (1) to recru...	Cell	Cellular Senescence	2,022
Markers and Biological Roles of Cellular Senescence	Although there is not a single unequivocal marker of cellular senescence, this process can be identified by the co-existence of a combination of features that, together, are specific and provide a molecular definition to the phenomenon: (1) lysosomal expansion, detectable by SABG; (2) upregulation of CDK inhibitors, pa...	Cell	Cellular Senescence	2,022
Senolytic Therapies and Mechanisms of Action	The strong association between cellular senescence and multiple pathologies has spurred the search for small chemical compounds that selectively kill senescent cells and that are referred to as senolytics. Senolysis (elimination of senescent cells) is very different from the cancellation of the senescence response, whi...	Cell	Cellular Senescence	2,022
Molecular Targets and Senolytic Compounds	The survival and apoptotic resistance of senescent cells strongly depends on the BCL2 family of proteins, especially BCLXL, but also BCL2 and BCLW. This renders senescent cells highly vulnerable to navitoclax, which targets these three proteins. Navitoclax has been evaluated in clinical trials for antitumor activity an...	Cell	Cellular Senescence	2,022
Emerging Immunological and Chemical Senolytics	Cardiac glycosides inhibit the plasma membrane Na+/K+-ATPase present in all cells causing a cationic imbalance and lowering the intracellular pH. The mechanism of senolysis by cardiac glycosides is likely connected to the vulnerability of senescent cells to low intracellular pH. Thus, chemical inhibition of glutaminase...	Cell	Cellular Senescence	2,022
Therapeutic Outlook for Senescence Targeting	In summary, cellular senescence is an important response to stress and damage that, in normal physiology, is followed by immune clearance, but that upon aging or chronic damage fails to be eliminated by immune mechanisms and hence is pathogenic due to the abundant secretion of pro-inflammatory and pro-fibrotic factors....	Cell	Cellular Senescence	2,022
Stem Cell Exhaustion and Aging	Aging is associated with reduced tissue renewal at steady state, as well as with impaired tissue repair upon injury, with each organ having its own strategy for renewal and repair. For example, in skeletal muscle, one single-cell type, the satellite cell, is placed at the apex of a unipotent and unidirectional hierarch...	Cell	Stem Cell Exhaustion	2,022
Injury-Induced Plasticity and Tissue Repair	Tissue repair is believed to rely to a large extent on injury-induced cellular de-differentiation and plasticity. For example, in the intestine, brain, and lung, injury induces de-differentiation of non-stem cells, which reactivates normally silent embryonic and stemness transcription programs, thus acquiring the plast...	Cell	Stem Cell Exhaustion	2,022
Cellular Reprogramming and Restoration of Stem Cell Function	A general strategy to counter the decline of stem cell function with aging is based on the concept of cellular reprogramming. This process is thought to act in a cell-autonomous manner on multiple cell types; however, its impact on stem and progenitor cells is considered of higher relevance because of its long-term imp...	Cell	Stem Cell Exhaustion	2,022
Cellular Reprogramming and Pluripotency	Cellular reprogramming toward pluripotency consists in the conversion of adult somatic cells into embryonic pluripotent cells (known as induced pluripotent stem cells or iPSCs) by the concomitant action of four externally transduced transcription factors, namely, OCT4, SOX2, KLF4, and MYC (OSKM). The process of reprogr...	Cell	Stem Cell Exhaustion	2,022
Partial Reprogramming and Cellular Rejuvenation	It is possible to initiate reprogramming with OSKM, interrupt the process at an intermediate state, and allow cells to return to their original identity. This transient cellular perturbation, variously known as partial, transient, or intermediate reprogramming, is able to rejuvenate cellular markers of aging such as th...	Cell	Stem Cell Exhaustion	2,022
Tissue Rejuvenation Through Transient Reprogramming	Transient reprogramming in mice confers repair capacity to old tissues so that a subsequent damage is repaired as efficiently as in young individuals. This increased repair capacity has been shown for models of tissue damage in the endocrine pancreas, skeletal muscle, nerve fibers, eye, skin, heart, and liver. Also, ti...	Cell	Stem Cell Exhaustion	2,022
Natural Tissue Repair and Reprogramming Convergence	Partial reprogramming recapitulates features of natural tissue repair. In both cases, cells undergo a transient process of de-differentiation, acquisition of embryonic and progenitor features, and subsequent re-differentiation. Thus, de- and re-differentiation could explain tissue rejuvenation, in line with the observa...	Cell	Stem Cell Exhaustion	2,022
Altered Intercellular Communication in Aging	Aging is coupled to progressive alterations in intercellular communication that increase systemic noise and compromise homeostatic and hormetic regulation. These changes lead to deficiencies in neural, neuroendocrine, and hormonal signaling pathways, including the adrenergic, dopaminergic, insulin/IGF1-based, and renin...	Cell	Altered Intercellular Communication	2,022
Systemic Effects and Meta-Cellular Hallmarks	Alterations in intercellular communication bridge the cell-intrinsic hallmarks to meta-cellular hallmarks, including the chronification of inflammatory reactions, the decline of immunosurveillance against pathogens and premalignant cells, and disruptions in bidirectional communication between the human genome and the m...	Cell	Altered Intercellular Communication	2,022
Research Directions and Mechanistic Insights	A number of studies have focused on identifying blood-borne systemic factors with pro-aging or pro-longevity properties, analyzing diverse communication systems between cells, and evaluating the functional relevance of extracellular matrix (ECM) disruption during aging. These investigations aim to understand how aging-...	Cell	Altered Intercellular Communication	2,022
Pro-Aging Blood-Borne Factors	A single transfusion of old blood induces features of aging in young mice within a few days, while dilution of old mouse blood with saline containing 5% albumin rejuvenates multiple tissues. This demonstrates the existence of circulating factors that promote aging. Among these pro-aging blood-borne factors, CCL11 (eota...	Cell	Altered Intercellular Communication	2,022
Anti-Aging Blood-Borne Factors	Soluble factors present in the blood of young mice effectively restore renewal and repair capacity in old mice. Heterochronic parabiosis experiments and single-cell transcriptomics confirm that young blood rejuvenates multiple tissues and restores age-related declines in gene expression, especially mitochondrial genes ...	Cell	Altered Intercellular Communication	2,022
Long-Range and Short-Range Communication Systems	The central nervous system regulates multiple aspects of aging across peripheral organs, demonstrating that brain-specific genetic manipulations—such as overexpression of SIRT1 or UCP1, or knockout of IKBKB and TRPV1—can extend mouse lifespan. The exact mechanisms underlying these long-range regulatory effects remain u...	Cell	Altered Intercellular Communication	2,022
Extracellular Matrix (ECM) and Aging	Aging leads to extensive damage in the extracellular matrix (ECM), including accumulation of advanced glycation end products (AGEs), carbonylation, carbamylation, elastin fragmentation, and collagen crosslinking, collectively resulting in tissue fibrosis ('fibroaging'). This process is driven in part by excessive TGF-β...	Cell	Altered Intercellular Communication	2,022
Chronic Inflammation (Inflammaging)	Aging is accompanied by a persistent low-grade inflammatory state known as 'inflammaging,' characterized by systemic and localized manifestations such as arteriosclerosis, neuroinflammation, osteoarthritis, and intervertebral disc degeneration. Circulating levels of pro-inflammatory cytokines and biomarkers, including ...	Cell	Altered Intercellular Communication	2,022
Links Between Inflammation and Other Aging Hallmarks	Chronic inflammation ('inflammaging') arises from multiple interconnected mechanisms associated with other hallmarks of aging. Genomic instability, mitochondrial dysfunction, impaired autophagy, and senescence all contribute to inflammatory signaling. For example, cytosolic translocation of nuclear and mitochondrial DN...	Cell	Chronic Inflammation and Hallmarks of Aging	2,023
Anti-Inflammatory and Anti-Aging Interventions	Inflammation functions both as a hallmark of aging and a key driver of other hallmarks, meaning that interventions targeting immune and inflammatory pathways can broadly influence lifespan and healthspan. Experimental models show that immune dysfunction alone can accelerate systemic aging: for instance, T cell-specific...	Cell	Chronic Inflammation and Anti-Aging Therapies	2,023
Dysbiosis and Aging	The gut microbiome plays a central role in host physiology, influencing nutrient digestion and absorption, immune defense, and the synthesis of vital metabolites such as vitamins, amino acid derivatives, secondary bile acids, and short-chain fatty acids (SCFAs). Beyond the gastrointestinal tract, gut microbes communica...	Cell	Dysbiosis and Aging	2,023
Microbiota Alterations in Aging	The gut microbiome exhibits significant variability among individuals due to genetic background, diet, lifestyle, and environmental factors, complicating efforts to link specific microbial changes to age-related diseases. Nonetheless, large-scale studies and meta-analyses have revealed reproducible patterns of microbio...	Cell	Gut Microbiota Alterations and Aging	2,023
Gut Dysbiosis in Progeria and Longevity	Multiomics studies in pathological aging have revealed that two different mouse models of progeria exhibit intestinal dysbiosis mainly characterized by an increase in the abundance of Proteobacteria and Cyanobacteria and a decrease in levels of Verrucomicrobia. Consistent with these findings, human progeria patients wi...	Cell	Fecal Microbiota Transplantation	2,023
FMT and Systemic Inflammation in Aging	FMT also revealed the causative role of gut dysbiosis in the chronic systemic inflammation and the decline in adaptive immunity associated with aging and age-related diseases. Transfer of the gut microbiota from old mice to young germ-free mice triggered inflammatory responses characterized by enhanced CD4+ T cell diff...	Cell	Fecal Microbiota Transplantation	2,023
Heterochronic FMT and Immune Rejuvenation	These works open the possibility of manipulating the gut microbiota with pre-, pro-, and post-biotics to rejuvenate the immune system and the aging brain. Heterochronic fecal transfers confirmed the causal link between age-dependent changes in microbial composition and a decline in the function of the host immune syste...	Cell	Fecal Microbiota Transplantation	2,023
Probiotic Interventions and Cognitive Aging	The probiotic Lactobacillus plantarum GKM3 promotes longevity and alleviates age-related cognitive impairment in the SAMP8 mouse model of accelerated aging. Interventions on gut microbiota composition also restored the age-linked decline in microglial maturation and function which causes altered brain plasticity and pr...	Cell	Gut Microbiota	2,023
Caloric Restriction and SCFA-Producing Bacteria	Caloric restriction diets induce structural changes of the gut microbiome increasing the abundance of Lactobacillus and other species that influence healthy aging. The gut microbiota-induced inflammaging and the consequent increase in insulin resistance can also be reversed by restoring abundance of beneficial SCFA-pro...	Cell	Gut Microbiota	2,023
Restoring Youthful Microbiome for Longevity	Collectively, these results underscore the causal links between aging and dysbiosis and suggest that interventions aimed at restoring a youthful microbiome may extend healthspan and lifespan.	Cell	Gut Microbiota	2,023
Interconnection of Hallmarks of Aging	All the 12 hallmarks of aging are strongly related among each other. For example, genomic instability (including that caused by telomere shortening) crosstalks to epigenetic alterations (e.g., through the loss-of-function mutation of epigenetic modifiers such as TET2), loss of proteostasis (e.g., due to the production ...	Cell	Hallmarks of Aging	2,023
Multitarget Anti-Aging Interventions	This entanglement is also visible at the level of experimental anti-aging interventions that often simultaneously target several hallmarks. Thus, SIRT activators including NAD+ precursors attenuate genomic instability (via DNA repair), epigenetic alterations (via histone deacetylation), loss of proteostasis (via the re...	Cell	Hallmarks of Aging	2,023
Primary, Antagonistic, and Integrative Hallmarks	Although each of the 12 hallmarks of aging can be targeted one by one, yielding tangible benefits for healthspan and lifespan, there is some kind of hierarchy among them. The primary hallmarks, which reflect damages affecting the genome, telomeres, epigenome, proteome, and organelles, progressively accumulate with time...	Cell	Hallmarks of Aging	2,023
Eight Hallmarks of Health and Systemic Integration	Recently, we postulated the existence of eight hallmarks of health, which include organizational features of spatial compartmentalization (integrity of barriers and containment of local perturbations), maintenance of homeostasis over time (recycling and turnover, integration of circuitries, and rhythmic oscillations), ...	Cell	Hallmarks of Aging	2,023
Heterochronic Parabiosis and Systemic Regulation of Aging	Heterochronic parabiosis experiments, in which the vascular systems of young and old mice are connected, illustrate the importance of systemic regulatory factors such as hormones and circulating cells in the aging process. This has been characterized at the single-cell transcriptomic level, revealing how young systemic...	Cell	Hallmarks of Aging	2,023
Strategies for Human Longevity Interventions	With the progress of longevity strategies in mammalian models and early clinical trials, it becomes crucial to design rational interventions for human aging. Strategies may involve avoidance of age-accelerating environmental factors (pollution, stress, inactivity, poor diets), adoption of health-promoting lifestyles (d...	Cell	Hallmarks of Aging	2,023
The Central Role of DNA Damage in the Ageing Process	Ageing is a complex, multifaceted process leading to widespread functional decline affecting every organ and tissue. Remarkably, it is still unknown if ageing has a unifying causal mechanism or is grounded in multiple sources. Phenotypically, the ageing process is associated with a wide variety of features at the molec...	Nature Reviews Molecular Cell Biology	DNA Damage and Aging	2,021
The Ultimate Cause of Ageing	There is wide agreement that ageing in metazoa is ultimately caused by the declining force of natural selection, once genes have been passed on to the next generation. Hence, mutations that only have adverse effects late in life, are not eliminated by purifying selection and therefore allowed to accumulate in the germl...	Nature Reviews Molecular Cell Biology	Evolutionary Basis of Aging	2,021
Evolutionary Logic and Proximate Causes of Ageing	While the evolutionary logic of ageing is clear, surprisingly little is known about its proximate causes, even though ageing is the source of most chronic diseases and the main burden for healthcare in advanced societies world-wide. Does ageing have a sheer infinite number of origins, as predicted by evolutionary theor...	Nature Reviews Molecular Cell Biology	DNA Damage and Aging	2,021
The Ultimate Cause of Ageing	There is wide agreement that ageing in metazoa is ultimately caused by the declining force of natural selection, once genes have been passed on to the next generation. Hence, mutations that only have adverse effects late in life, are not eliminated by purifying selection and therefore allowed to accumulate in the germl...	Nature Reviews Molecular Cell Biology	Evolutionary Basis of Aging	2,021
Evolutionary Logic and Proximate Causes of Ageing	While the evolutionary logic of ageing is clear, surprisingly little is known about its proximate causes, even though ageing is the source of most chronic diseases and the main burden for healthcare in advanced societies world-wide. Does ageing have a sheer infinite number of origins, as predicted by evolutionary theor...	Nature Reviews Molecular Cell Biology	DNA Damage and Aging	2,021
Genome Instability at Dysfunctional Telomeres	The discovery in the late 1980s that S. cerevisiae “ever shorter telomeres” (EST1) mutants undergo replicative senescence has popularized the concept that progressive telomere shortening drives the ageing process. In mammals, telomeres consist of thousands of TTAGGG repeats covered by the shelterin complex that facilit...	Nature Reviews Molecular Cell Biology	Telomere Shortening and Aging	2,021

End of preview.

Dataset Summary

A collection of curated text chunks designed for retrieval-augmented generation (RAG) in the domain of biological aging and longevity.

The chunks are intended to provide contextual scientific evidence for language models rather than standalone answers.

Data Sources

PubMed-indexed scientific literature
Review articles and primary research in aging biology

Intended Use

RAG pipelines and vector database indexing
Evidence-grounded scientific question answering

Not Intended Use

Medical or clinical decision-making
Health or treatment recommendations

License

Released for research and educational use. Users must comply with the licenses of the original source materials.

Downloads last month: 6

Total file size:

3.14 MB