Chromosome Termini Research Articles

Telomeric RNA (TERRA) increases in response to spaceflight and high-altitude climbing

Telomeres are repetitive nucleoprotein complexes at chromosomal termini essential for maintaining genome stability. Telomeric RNA, or TERRA, is a previously presumed long noncoding RNA of heterogeneous lengths that contributes to end-capping structure and function, and facilitates telomeric recombination in tumors that maintain telomere length via the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. Here, we investigated TERRA in the radiation-induced DNA damage response (DDR) across astronauts, high-altitude climbers, healthy donors, and cellular models. Similar to astronauts in the space radiation environment and climbers of Mt. Everest, in vitro radiation exposure prompted increased transcription of TERRA, while simulated microgravity did not. Data suggest a specific TERRA DDR to telomeric double-strand breaks (DSBs), and provide direct demonstration of hybridized TERRA at telomere-specific DSB sites, indicative of protective TERRA:telomeric DNA hybrid formation. Targeted telomeric DSBs also resulted in accumulation of TERRA foci in G2-phase, supportive of TERRA’s role in facilitating recombination-mediated telomere elongation. Results have important implications for scenarios involving persistent telomeric DNA damage, such as those associated with chronic oxidative stress (e.g., aging, systemic inflammation, environmental and occupational radiation exposures), which can trigger transient ALT in normal human cells, as well as for targeting TERRA as a therapeutic strategy against ALT-positive tumors.

The TERT Promoter is Polycomb-Repressed in Neuroblastoma Cells with Long Telomeres.

The epigenetic landscape of the TERT locus is unique in neuroblastoma. The DNA at the TERT locus, unlike other cancer cells and similar to normal cells, are hypomethylated in telomerase-positive neuroblastoma cells. The TERT locus is repressed by polycomb repressive complex-2 complex in neuroblastoma cells that have long telomeres and do not express TERT. Long telomeres in neuroblastoma cells are also associated with repressive chromatin states at the chromosomal termini, suggesting TPE.

Longer prostate stromal cell telomere length is associated with increased risk of death from other cancers.

Telomeres are located at chromosomal termini and function to maintain genomic integrity. Telomere dysfunction is a well-recognized contributor to aging and age-related diseases, such as prostate cancer. Since telomere length is highly heritable, we postulate that stromal cell telomere length in the tissue of a particular solid organ may generally reflect constitutive stromal cell telomere length in other solid organs throughout the body. Even with telomere loss occurring with each round of cell replication, in general, telomere length in prostate stromal cells in mid-life would still be correlated with the telomere length in stromal cells in other organs. Thus, we hypothesize that prostate stromal cell telomere length and/or telomere length variability is a potential indicator of the likelihood of developing future solid cancers, beyond prostate cancer, and especially lethal cancer. To explore this hypothesis, we conducted a cohort study analysis of 1,175 men who were surgically treated for prostate cancer and were followed for death, including from causes other than their prostate cancer. In this cohort study with a median follow-up of 19 years, we observed that longer prostate stromal cell telomere length measured in tissue microarray spots containing prostate cancer was associated with an increased risk of death from other solid cancers. Variability in telomere length among these prostate stromal cells was possibly positively associated with risk of death from other solid cancers. Studying the link between stromal cell telomere length and cancer mortality may be important for guiding the development of cancer interception and prevention strategies.

Use of peptide nucleic acid probe to determine telomere dynamics in improving chromosome analysis in genetic toxicology studies

Genetic toxicology, strategically located at the intersection of genetics and toxicology, aims to demystify the complex interplay between exogenous agents and our genetic blueprint. Telomeres, the protective termini of chromosomes, play instrumental roles in cellular longevity and genetic stability. Traditionally karyotyping and fluorescence in situ hybridisation (FISH), have been indispensable tools for chromosomal analysis following exposure to genotoxic agents. However, their scope in discerning nuanced molecular dynamics is limited. Peptide Nucleic Acids (PNAs) are synthetic entities that embody characteristics of both proteins and nucleic acids and have emerged as potential game-changers. This perspective report comprehensively examines the vast potential of PNAs in genetic toxicology, with a specific emphasis on telomere research. PNAs' superior resolution and precision make them a favourable choice for genetic toxicological assessments. The integration of PNAs in contemporary analytical workflows heralds a promising evolution in genetic toxicology, potentially revolutionizing diagnostics, prognostics, and therapeutic avenues. In this timely review, we attempted to assess the limitations of current PNA-FISH methodology and recommend refinements.

Subtelomeric plasticity contributes to gene family expansion in the human parasitic flatworm Schistosoma mansoni

BackgroundThe genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some parasites, genes associated with proliferation, invasion, and survival are often found in these regions, where they benefit from the subtelomere's highly plastic, rapidly changing nature. The increasing availability of complete (or near complete) parasite genomes provides an opportunity to investigate these typically poorly defined and overlooked genomic regions and potentially reveal relevant gene families necessary for the parasite’s lifestyle.ResultsUsing the latest chromosome-scale genome assembly and hallmark repeat richness observed at chromosome termini, we have identified and characterised the subtelomeres of Schistosoma mansoni, a metazoan parasitic flatworm that infects over 250 million people worldwide. Approximately 12% of the S. mansoni genome is classified as subtelomeric, and, in line with other organisms, we find these regions to be gene-poor but rich in transposable elements. We find that S. mansoni subtelomeres have undergone extensive interchromosomal recombination and that these sites disproportionately contribute to the 2.3% of the genome derived from segmental duplications. This recombination has led to the expansion of subtelomeric gene clusters containing 103 genes, including the immunomodulatory annexins and other gene families with unknown roles. The largest of these is a 49-copy plexin domain-containing protein cluster, exclusively expressed in the tegument—the tissue located at the host-parasite physical interface—of intramolluscan life stages.ConclusionsWe propose that subtelomeric regions act as a genomic playground for trial-and-error of gene duplication and subsequent divergence. Owing to the importance of subtelomeric genes in other parasites, gene families implicated in this subtelomeric expansion within S. mansoni warrant further characterisation for a potential role in parasitism.

Mid-cell migration of the chromosomal terminus is coupled to origin segregation in Escherichia coli

Bacterial chromosomes are dynamically and spatially organised within cells. In slow-growing Escherichia coli, the chromosomal terminus is initially located at the new pole and must therefore migrate to midcell during replication to reproduce the same pattern in the daughter cells. Here, we use high-throughput time-lapse microscopy to quantify this transition, its timing and its relationship to chromosome segregation. We find that terminus centralisation is a rapid discrete event that occurs ~25 min after initial separation of duplicated origins and ~50 min before the onset of bulk nucleoid segregation but with substantial variation between cells. Despite this variation, its movement is tightly coincident with the completion of origin segregation, even in the absence of its linkage to the divisome, suggesting a coupling between these two events. Indeed, we find that terminus centralisation does not occur if origin segregation away from mid-cell is disrupted, which results in daughter cells having an inverted chromosome organisation. Overall, our study quantifies the choreography of origin-terminus positioning and identifies an unexplored connection between these loci, furthering our understanding of chromosome segregation in this bacterium.

Telomere sequence variability in genotypes from natural plant populations: unusual block-organized double-monomer terminal telomeric arrays

BackgroundTelomeres are the nucleoprotein complexes that physically cap the ends of eukaryotic chromosomes. Most plants possess Arabidopsis-type telomere sequences (TSs). In addition to terminal TSs, more diverse interstitial TSs exists in plants. Although telomeres have been sufficiently studied, the actual diversity of TSs in land plants is underestimated.ResultsWe investigate genotypes from seven natural populations with contrasting environments of four Chenopodium species to reveal the variability in TSs by analyzing Oxford Nanopore reads. Fluorescent in situ hybridization was used to localize telomeric repeats on chromosomes. We identified a number of derivative monomers that arise in part of both terminal and interstitial telomeric arrays of a single genotype. The former presents a case of block-organized double-monomer telomers, where blocks of Arabidopsis-type TTTAGGG motifs were interspersed with blocks of derivative TTTAAAA motifs. The latter is an integral part of the satellitome with transformations specific to the inactive genome fraction.ConclusionsWe suggested two alternative models for the possible formation of derivative monomers from telomeric heptamer motifs of Arabidopsis-type. It was assumed that derivatization of TSs is a ubiquitous process in the plant genome but occurrence and frequencies of derivatives may be genotype-specific. We also propose that the formation of non-canonical arrays of TSs, especially at chromosomal termini, may be a source for genomic variability in nature.

Characterization of a pathway of genomic instability induced by R-loops and its regulation by topoisomerases in E. coli.

The prototype enzymes of the ubiquitous type IA topoisomerases (topos) family are Escherichia coli topo I (topA) and topo III (topB). Topo I shows preference for relaxation of negative supercoiling and topo III for decatenation. However, as they could act as backups for each other or even share functions, strains lacking both enzymes must be used to reveal the roles of type IA enzymes in genome maintenance. Recently, marker frequency analysis (MFA) of genomic DNA from topA topB null mutants revealed a major RNase HI-sensitive DNA peak bordered by Ter/Tus barriers, sites of replication fork fusion and termination in the chromosome terminus region (Ter). Here, flow cytometry for R-loop-dependent replication (RLDR), MFA, R-loop detection with S9.6 antibodies, and microscopy were used to further characterize the mechanism and consequences of over-replication in Ter. It is shown that the Ter peak is not due to the presence of a strong origin for RLDR in Ter region; instead RLDR, which is partly inhibited by the backtracking-resistant rpoB*35 mutation, appears to contribute indirectly to Ter over-replication. The data suggest that RLDR from multiple sites on the chromosome increases the number of replication forks trapped at Ter/Tus barriers which leads to RecA-dependent DNA amplification in Ter and to a chromosome segregation defect. Overproducing topo IV, the main cellular decatenase, does not inhibit RLDR or Ter over-replication but corrects the chromosome segregation defect. Furthermore, our data suggest that the inhibition of RLDR by topo I does not require its C-terminal-mediated interaction with RNA polymerase. Overall, our data reveal a pathway of genomic instability triggered by R-loops and its regulation by various topos activities at different steps.

PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment

Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts and covalently PARylates TRF1 in S-phase modifying its DNA affinity. Therefore, genetic and pharmacological inhibition of PARP1 impairs the dynamic association of TRF1 and the bromodeoxyuridine incorporation at replicating telomeres. Inhibition of PARP1 also affects the recruitment of WRN and BLM helicases in TRF1 containing complexes during S-phase, triggering replication-dependent DNA-damage and telomere fragility. This work unveils an unprecedented role for PARP1 as a “surveillant” of telomere replication, which orchestrates protein dynamics at proceeding replication fork.

Introgression of chromosome 6PL terminal segment from Agropyron cristatum to increase both grain number and grain weight in wheat

Agropyron cristatum (2n = 4x = 28, PPPP), which harbours many high-yield and disease-resistance genes, is a promising donor for wheat improvement. Narrow genetic diversity and the trade-off between grain weight and grain number have become bottlenecks for increasing grain yield in wheat. In this study, a novel translocation line, WAT650l, was derived from the chromosome 6P addition line 4844–12, which can simultaneously increase both grain number per spike (GNS) and thousand-grain weight (TGW). Cytological analysis and molecular marker analysis revealed that WAT650l was a 5BL·5BS-6PL (bin 12–17) translocation line. Assessment of agronomic traits and analysis of the BC4F2 and BC5F2 populations suggested that the 6PL terminal chromosome segment in WAT650l resulted in increased grain number per spike (average increased by 14.07 grains), thousand-grain weight (average increased by 4.31 g), flag leaf length, plant height, spikelet number per spike and kernel number per spikelet during the two growing seasons of 2020–2021 and 2021–2022. Additionally, the increased GNS locus and high-TGW locus of WAT650l were mapped to the bins 16–17 and 12–13, respectively, on chromosome 6PL by genetic population analysis of three translocation lines. In summary, we provide a valuable germplasm resource for broadening the genetic base of wheat and overcoming the negative relationship between GNS and TGW in wheat breeding.

Bipartite Genomes in Enterobacterales: Independent Origins of Chromids, Elevated Openness and Donors of Horizontally Transferred Genes

Multipartite bacteria have one chromosome and one or more chromid. Chromids are believed to have properties that enhance genomic flexibility, making them a favored integration site for new genes. However, the mechanism by which chromosomes and chromids jointly contribute to this flexibility is not clear. To shed light on this, we analyzed the openness of chromosomes and chromids of the two bacteria, Vibrio and Pseudoalteromonas, both which belong to the Enterobacterales order of Gammaproteobacteria, and compared the genomic openness with that of monopartite genomes in the same order. We applied pangenome analysis, codon usage analysis and the HGTector software to detect horizontally transferred genes. Our findings suggest that the chromids of Vibrio and Pseudoalteromonas originated from two separate plasmid acquisition events. Bipartite genomes were found to be more open compared to monopartite. We found that the shell and cloud pangene categories drive the openness of bipartite genomes in Vibrio and Pseudoalteromonas. Based on this and our two recent studies, we propose a hypothesis that explains how chromids and the chromosome terminus region contribute to the genomic plasticity of bipartite genomes.

Thyroid carcinoma-featured telomerase activation and telomere maintenance: Biology and translational/clinical significance.

Telomerase is a ribonucleoprotein complex consisting of a catalytic component telomerase reverse transcriptase (TERT), internal RNA template and other co-factors, and its essential function is to synthesize telomeric DNA, repetitive TTAGGG sequences at the termini of linear chromosomes. Telomerase is silent in normal human follicular thyroid cells, primarily due to the TERT gene being tightly repressed. During the development and progression of thyroid carcinomas (TCs), TERT induction and telomerase activation is in general required to maintain telomere length, thereby conferring TC cells with immortal and aggressive phenotypes. The genomic alterations of the TERT loci including TERT promoter's gain-of-function mutations, copy number gain, fusion and rearrangements, have recently been identified in TCs as mechanisms to induce TERT expression and to activate telomerase. Importantly, numerous studies have consistently shown that TERT promoter mutations and TERT expression occur in all TC subtypes, and are robustly associated with TC malignancy, aggressiveness, treatment failure and poor outcomes. Therefore, the assessment of TERT promoter mutations and TERT expression is highly valuable in TC diagnostics, prognosis, treatment decision, and follow-up design. In addition, the TERT promoter is frequently hypermethylated in TC cells and tumors, which is required to activate TERT transcription and telomerase. Dysregulation of other components in the telomerase complex similarly upregulate telomerase. Moreover, shortened telomeres lead to altered gene expression and metabolism, thereby actively promoting TC aggressiveness. Here we summarize recent findings in TCs to provide the landscape of TC-featured telomere/telomerase biology and discuss underlying implications in TC precision medicine. Mechanistic insights into telomerase activation and TERT induction in TCs are important both biologically and clinically. The TERT gene aberration and expression-based molecular classification of TCs is proposed, and for such a purpose, the standardization of the assay and evaluation system is required. Moreover, the TERT-based system and 2022 WHO TC classification may be combined to improve TC care.

PSVIII-B-3 Comparison of Telomere Length in Leukocytes of Control and Prenatally Stressed Brahman Bull and Heifer Calves

Abstract Telomeres are comprised of G-rich nucleotide sequences (5’-TTAGGG-3’) at the chromosome termini that are responsible for protecting chromosomes; however, attrition of these sequences has been observed due to aging and stress. The purpose of this study was to compare telomere length (TL) in control and prenatally stressed (PNS) calves. Mature Brahman cows inseminated to a single Brahman sire in 2018 were assigned to be either Control (n=35; not transported) or PNS (n=37; 2 h of transportation at 60, 80, 100, 120, and 140±5 d of gestation). Jugular blood samples were obtained by venipuncture from 10 Control (5 bulls and 5 heifers) and 10 PNS (5 bulls and 5 heifers) calves at 25±2 d of age. Peripheral leukocytes were isolated and genomic DNA was extracted utilizing silicone membrane spin column kits. The relative quantity of telomere products, which is proportional to the average TL, was determined by multiplex quantitative PCR analysis using the ratio of bovine telomere and β-globulin DNA (T/S ratio). An absolute standard of bovine telomere (1012–107 dilution series) and β-globulin (109-104 dilution series) genes was utilized to produce relative copy number. All samples were processed in triplicate and samples were included if the triplicate Cq difference was less than 0.25 cycles. Data were analyzed using ANOVA. TL differed by sex (P< 0.03; bulls 11,959±211; heifers 12,850±366) and treatment (P< 0.02; Control 12,895±278; PNS 11,913±303). There was not an interaction of sex and treatment (P >0.43) although TL of Control heifers (13,482±396) exceeded the TL of PNS bulls (11,609±348). These observations of fewer copies of telomere sequences suggest an influence of sex on TL within 1 month of age; and, that prenatal transportation stress may increase attrition of telomeres in cattle. Support: USDA NIFA Award No. 2019-67015-29573

Role for DNA double strand end-resection activity of RecBCD in control of aberrant chromosomal replication initiation in Escherichia coli.

Replication of the circular bacterial chromosome is initiated from a locus oriC with the aid of an essential protein DnaA. One approach to identify factors acting to prevent aberrant oriC-independent replication initiation in Escherichia coli has been that to obtain mutants which survive loss of DnaA. Here, we show that a ΔrecD mutation, associated with attenuation of RecBCD’s DNA double strand end-resection activity, provokes abnormal replication and rescues ΔdnaA lethality in two situations: (i) in absence of 5′-3′ single-strand DNA exonuclease RecJ, or (ii) when multiple two-ended DNA double strand breaks (DSBs) are generated either by I-SceI endonucleolytic cleavages or by radiomimetic agents phleomycin or bleomycin. One-ended DSBs in the ΔrecD mutant did not rescue ΔdnaA lethality. With two-ended DSBs in the ΔrecD strain, ΔdnaA viability was retained even after linearization of the chromosome. Data from genome-wide DNA copy number determinations in ΔdnaA-rescued cells lead us to propose a model that nuclease-mediated DNA resection activity of RecBCD is critical for prevention of a σ-mode of rolling-circle over-replication when convergent replication forks merge and fuse, as may be expected to occur during normal replication at the chromosomal terminus region or during repair of two-ended DSBs following ‘ends-in’ replication.

FISH Mapping of Telomeric and Non-Telomeric (AG3T3)3 Reveal the Chromosome Numbers and Chromosome Rearrangements of 41 Woody Plants.

Data for the chromosomal FISH mapping localization of (AG3T3)3 are compiled for 37 species belonging 27 families; for 24 species and 14 families, this is the first such report. The chromosome number and length ranged from 14–136 and 0.56–14.48 μm, respectively. A total of 23 woody plants presented chromosome length less than 3 μm, thus belonging to the small chromosome group. Telomeric signals were observed at each chromosome terminus in 38 plants (90.5%) and were absent at several chromosome termini in only four woody plants (9.5%). Non-telomeric signals were observed in the chromosomes of 23 plants (54.8%); in particular, abundant non-telomeric (AG3T3)3 was obviously observed in Chimonanthus campanulatus. Telomeric signals outside of the chromosome were observed in 11 woody plants (26.2%). Overall, ten (AG3T3)3 signal pattern types were determined, indicating the complex genome architecture of the 37 considered species. The variation in signal pattern was likely due to chromosome deletion, duplication, inversion, and translocation. In addition, large primary constriction was observed in some species, probably due to or leading to chromosome breakage and the formation of new chromosomes. The presented results will guide further research focused on determining the chromosome number and disclosing chromosome rearrangements of woody plants.

Neural Markers of Auditory Response and Habituation in Phelan-McDermid Syndrome.

Phelan-McDermid Syndrome (PMS) is a rare genetic disorder caused by deletion or sequence variation in the SHANK3 gene at terminal chromosome 22 that confers high likelihood of comorbid autism spectrum disorder (ASD). Whereas individuals with idiopathic ASD (iASD) can demonstrate diverse patterns of sensory differences, PMS is mainly characterized by sensory hyporesponsiveness. This study used electrophysiology and a passive auditory habituation paradigm to test for neural markers of hyporesponsiveness. EEG was recorded from 15 individuals with PMS, 15 with iASD, and 16 with neurotypical development (NT) while a series of four consecutive 1,000 Hz tones was repeatedly presented. We found intact N1, P2, and N2 event-related potentials (ERPs) and habituation to simple auditory stimuli, both in individuals with iASD and in those with PMS. Both iASD and PMS groups showed robust responses to the initial tone and decaying responses to each subsequent tone, at levels comparable to the NT control group. However, in PMS greater initial N1 amplitude and habituation were associated with auditory hypersensitivity, and P2 habituation correlated with ASD symptomatology. Additionally, further classification of the PMS cohort into genetic groupings revealed dissociation of initial P2 amplitude and habituation of N1 based on whether the deletions included additional genes beyond solely SHANK3 and those not thought to contribute to phenotype. These results provide preliminary insight into early auditory processing in PMS and suggest that while neural response and habituation is generally preserved in PMS, genotypic and phenotypic characteristics may drive some variability. These initial findings provide early evidence that the robust pattern of behavioral hyporesponsiveness in PMS may be due, at least in audition, to higher order factors.

Genetic and Epigenetic Inheritance at Telomeres.

Transgenerational inheritance can occur at telomeres in distinct contexts. Deficiency for telomerase or telomere-binding proteins in germ cells can result in shortened or lengthened chromosome termini that are transmitted to progeny. In human families, altered telomere lengths can result in stem cell dysfunction or tumor development. Genetic inheritance of altered telomeres as well as mutations that alter telomeres can result in progressive telomere length changes over multiple generations. Telomeres of yeast can modulate the epigenetic state of subtelomeric genes in a manner that is mitotically heritable, and the effects of telomeres on subtelomeric gene expression may be relevant to senescence or other human adult-onset disorders. Recently, two novel epigenetic states were shown to occur at C. elegans telomeres, where very low or high levels of telomeric protein foci can be inherited for multiple generations through a process that is regulated by histone methylation.Together, these observations illustrate that information relevant to telomere biology can be inherited via genetic and epigenetic mechanisms, although the broad impact of epigenetic inheritance to human biology remains unclear.

Dissection of structural heterogeneity in human telomerase RNA

Telomeres safeguard the genome by suppressing illicit DNA damage responses at chromosome termini. To compensate for incomplete DNA replication at telomeres, most continually dividing cells express the telomerase ribonucleoprotein (RNP) complex. Telomerase maintains telomere length by synthesizing short DNA repeats using an internal telomerase RNA (TR) template. The catalytic activity of telomerase is a key stimulator of human cancers, while conversely, telomerase deficiency is a root cause of ‘telomeropathies', a spectrum of genetic diseases arising from extreme telomere shortening.

Different modes of spacer acquisition by the Staphylococcus epidermidis type III-A CRISPR-Cas system.

CRISPR-Cas systems provide prokaryotic organisms with an adaptive defense mechanism that acquires immunological memories of infections. This is accomplished by integration of short fragments from the genome of invaders such as phages and plasmids, called ‘spacers’, into the CRISPR locus of the host. Depending on their genetic composition, CRISPR-Cas systems can be classified into six types, I-VI, however spacer acquisition has been extensively studied only in type I and II systems. Here, we used an inducible spacer acquisition assay to study this process in the type III-A CRISPR-Cas system of Staphylococcus epidermidis, in the absence of phage selection. Similarly to type I and II spacer acquisition, this type III system uses Cas1 and Cas2 to preferentially integrate spacers from the chromosomal terminus and free dsDNA ends produced after DNA breaks, in a manner that is enhanced by the AddAB DNA repair complex. Surprisingly, a different mode of spacer acquisition from rRNA and tRNA loci, which spans only the transcribed sequences of these genes and is not enhanced by AddAB, was also detected. Therefore, our findings reveal both common mechanistic principles that may be conserved in all CRISPR-Cas systems, as well as unique and intriguing features of type III spacer acquisition.

Dužina telomera kao biomarker starenja i bolesti

As research related to healthspan and lifespan has become a hot topic, the necessity for a reliable and practical biomarker of aging (BoA), which can provide information about mortality and morbidity risk, along with remaining life expectancy, has increased. The chromosome terminus non-coding protective structure that prevents genomic instability is called a telomere. The continual shortening of telomeres, which affects their structure as well as function, is a hallmark of agedness. The aforementioned process is a potential cause of age-related diseases (ARDs), leading to a bad prognosis and a low survival rate, which compromise health and longevity. Hence, studies scrutinizing the BoAs often include telomere length (TL) as a prospective candidate. The results of these studies suggest that TL measurement can only provide an approximate appraisal of the aging rate, and its implementation into clinical practice and routine use as a BoA has many limitations and challenges. Nevertheless, measuring TL while determining other biomarkers can be used to assess biological age. This review focuses on the importance of telomeres in health, senescence, and diseases, as well as on summarizing the results and conclusions of previous studies evaluating TL as a potential BoA.