RESUMO
BACKGROUND: The aging population prompts studying risk factors and markers to predict healthy aging. Telomere length is a promising candidate for assessing various age-related traits. AIM OF THE STUDY: To investigate the association between physical performance and telomere length. METHODS: We enrolled 323 older Mexican adults from the "Cohort of Obesity, Sarcopenia, and Frailty of Older Mexican Adults" affiliated with the Instituto Mexicano del Seguro Social and assessed their physical performance using the Short Physical Performance Battery, dividing participants into low (≤7) and high (>7) groups. Absolute telomere length was determined by qPCR, and individuals were classified into short (≤4.22 kb) and long (>4.22 kb) groups. We calculated the mean and adjusted mean, considering sex and age, among others, with 95% CI. We estimated the effect size between physical performance and telomere length using Cohen's d for unequal group sizes and calculated the odds ratio for physical performance based on telomere length. RESULTS: Participants with low physical performance had significantly shorter telomeres (mean 4.14.44.7 kb, adjusted mean 3.54.04.5 kb, p <0.001), while those with high physical performance exhibited longer telomeres (mean 5.55.75.9 kb, adjusted mean 4.75.35.8 kb, p <0.001), with a medium-to-high telomere length effect size (d = 0.762). The odds of low physical activity increased 2.13.66.1-fold per kb of telomere attrition (adjOR 1.73.36.3, p <0.001). CONCLUSION: Decreased physical function is associated with shorter telomere length. Absolute telomere length presents a promising biomarker for distinguishing between healthy and unhealthy aging, warranting further investigation.
Assuntos
Desempenho Físico Funcional , Telômero , Humanos , Masculino , Feminino , Idoso , México , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Envelhecimento/fisiologia , Envelhecimento/genética , Encurtamento do Telômero , Homeostase do Telômero , Fragilidade/genéticaRESUMO
BACKGROUND: Telomere length (TL) shortening has been identified as a marker of aging and associated with adverse health outcomes, but evidence of its association with sarcopenia is inconclusive. AIMS: Estimate the cross-sectional and prospective associations between TL and sarcopenia. METHODS: We used data from Waves 3 and 4 (2017, 2021) of the Study on Global Aging and Adult Health in Mexico (SAGE-Mexico). The cross-sectional sample consisted of 1,738 adults aged 50 and older, and the longitudinal sample consisted of 1,437. Relative TL was determined by real-time quantitative polymerase chain reaction (qPCR) on DNA extracted from saliva samples and quantified as the telomere/single-copy gene (T/S) ratio. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People (EWGSOP2). RESULTS: The mean salivary TL was 1.50 T/S units (95% CI: 1.49-1.52). The baseline prevalence of sarcopenia was 13.3% (95% CI: 9.8-16.8%). The incidence and persistence of sarcopenia were 6.8% (95% CI: 5.0-9.5%) and 7.0% (95% CI: 5.1-9.6%), respectively. The results showed that a one standard deviation decrease in TL was cross-sectionally associated with higher odds of sarcopenia (OR = 1.31; 95% CI: 1.03-1.67) and prospectively with a higher incidence (RRR = 1.55; 95% CI: 1.06-2.25) and persistence (RRR = 1.50; 95% CI: 1.01-2.24) of sarcopenia. CONCLUSIONS: Older adults with shorter TL had higher rates of incident and persistent sarcopenia. Implementation of interventions to delay the decline of TL in older adults is warranted. Further translational studies are needed to elucidate the effects of exercise or diet on DNA repair in the telomeric region and their associations with sarcopenia.
Assuntos
Sarcopenia , Humanos , Sarcopenia/epidemiologia , Sarcopenia/genética , Feminino , Masculino , Estudos Transversais , Idoso , Pessoa de Meia-Idade , Incidência , Prevalência , México/epidemiologia , Estudos Prospectivos , Telômero/genética , Encurtamento do Telômero , Estudos Longitudinais , Idoso de 80 Anos ou mais , Saliva/metabolismo , Saliva/química , Envelhecimento/genéticaRESUMO
BACKGROUND: Shortening telomere length (TL) is an important ageing marker associated with substance use disorder (SUD). However, the influence of psychiatric and clinical comorbidities and alcohol-related outcomes has not been much explored in the context of TL in individuals with alcohol use disorder (AUD) and may be a source of heterogeneity in AUD studies. Therefore, our aim was to investigate the influence of AUD, alcohol-related outcomes, and common psychiatric comorbidities on TL in men with AUD and healthy controls (HC). METHODS: Men with AUD (n = 108, mean age = 52.4, SD = 8.6) were recruited in a detoxification unit, and HC (n = 80, mean age = 50.04, SD = 9.1) from the blood bank, both located in Brazil. HC had no current or lifetime diagnosis of any substance use disorder. Psychiatric comorbidities were assessed using SCID-I. TL ratio was measured in triplicates using quantitative multiplex PCR. RESULTS: Telomere length did not differ between individuals with AUD and HC (p = 0.073) or was associated with AUD-related outcomes, trauma, or clinical comorbidities. Individuals with externalizing disorders had longer TL when comparing with those with internalizing disorders (p = 0.018) or without comorbidity (p = 0.018). CONCLUSION: Our findings indicate that TL was influenced by the presence of psychiatric comorbidity rather than case or control status. These results were adjusted for potential confounders, such as age.
Assuntos
Alcoolismo , Comorbidade , Encurtamento do Telômero , Humanos , Masculino , Brasil/epidemiologia , Alcoolismo/epidemiologia , Alcoolismo/genética , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , TelômeroRESUMO
Se exponen los hallazgos históricos y la importancia biológica de los telómeros en la vida celular y en los aspectos genéticos del ADN humano. (AU)
The discovery and the biological importance of the telomeres are exposed. (AU)
Assuntos
Humanos , DNA/genética , Telômero/fisiologia , Telômero/genética , Telomerase/fisiologia , Telomerase/genética , Envelhecimento/fisiologia , DNA/metabolismo , Senescência Celular , Telomerase/metabolismo , Replicação do DNA/fisiologia , Encurtamento do Telômero , Neoplasias/fisiopatologiaRESUMO
Cellular senescence is a state of permanent growth arrest. It can be triggered by telomere shortening (replicative senescence) or prematurely induced by stresses such as DNA damage, oncogene overactivation, loss of tumor suppressor genes, oxidative stress, tissue factors, and others. Advances in techniques and experimental designs have provided new evidence about the biology of senescent cells (SnCs) and their importance in human health and disease. This review aims to describe the main aspects of SnCs phenotype focusing on alterations in subcellular compartments like plasma membrane, cytoskeleton, organelles, and nuclei. We also discuss the heterogeneity, dynamics, and plasticity of SnCs' phenotype, including the SASP, and pro-survival mechanisms. We advance on the multiple layers of phenotypic heterogeneity of SnCs, such as the heterogeneity between inducers, tissues and within a population of SnCs, discussing the relevance of these aspects to human health and disease. We also raise the main challenges as well alternatives to overcome them. Ultimately, we present open questions and perspectives in understanding the phenotype of SnCs from the perspective of basic and applied questions.
Assuntos
Senescência Celular , Encurtamento do Telômero , Humanos , Senescência Celular/genética , Fenótipo , Células Cultivadas , Estresse OxidativoRESUMO
Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere lengthening, increased body mass index (BMI) is associated with telomere erosion. We sought to compare leukocyte telomere length (LTL) in PCOS women with normal, overweight, and obese BMI. We evaluated the relationship between LTL and clinical variables of PCOS and inflammatory biomarkers independent of BMI. A total of 348 women (243 PCOS and 105 non-PCOS) were evaluated for anthropometric measures, total testosterone, androstenedione, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting insulin and glycemia, lipid profile, homocysteine, C-reactive protein (CRP) and homeostatic model of insulin resistance (HOMA-IR). LTL was measured by qPCR. The PCOS group presented higher weight, waist circumference, BMI, testosterone, LH, fasting insulin, FAI, and HOMA-IR, and lower E2, SHBG, and fasting glycemia measures compared with the non-PCOS. When stratified by BMI, LTL was increased in all subgroups in PCOS compared to non-PCOS. However, in the PCOS group, LTL was lower in overweight (P = 0.0187) and obese (P = 0.0018) compared to normal-weight women. The generalized linear model showed that BMI, androstenedione, homocysteine, and CRP were associated with telomere biology. Women with PCOS had longer LTL, however, overweight or obesity progressively contributes to telomere shortening and may affect reproductive outcomes of PCOS, while androstenedione may increase LTL.
Assuntos
Índice de Massa Corporal , Obesidade , Síndrome do Ovário Policístico , Encurtamento do Telômero , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/metabolismo , Feminino , Obesidade/genética , Obesidade/sangue , Adulto , Adulto Jovem , Resistência à Insulina , Telômero/metabolismo , Leucócitos/metabolismo , Biomarcadores/sangueRESUMO
Despite current literature pointing to a link between shortened telomeres and aging, chronic diseases, and geriatric syndromes, the precise implications of this connection remain unclear. The aim of this exploratory, cross-sectional, observational study was to investigate the association between the relative telomere length (RTL) of peripheral blood leukocyte subtypes (mononuclear cells and granulocytes) and physical performance using the Short Physical Performance Battery (SPPB) in older adults. A cohort of 95 participants was recruited, which included men and women aged over 60 years (70.48 ± 5.5 years). It was found that mononuclear cell RTL was significantly lower than that of granulocytes (p < 0.0001). Moreover, individuals with good SPPB performance exhibited lower mononuclear cell RTL compared with those with moderate or poor performance. However, no significant differences were observed in granulocyte RTL between different SPPB performance groups. The global SPPB score showed an inverse correlation with mononuclear cell RTL, but this correlation was not present with granulocyte RTL. Similarly, the SPPB sit-to-stand domain correlated with mononuclear cell RTL, but no such correlation was found with granulocyte RTL. Our findings challenge conventional expectations, suggesting that shorter mononuclear cell RTL may be associated with favorable functional capacity. The variations in RTL between mononuclear cells and granulocytes highlight their distinct biological roles and turnover rates. A history of immune responses may influence mononuclear cell RTL dynamics, while telomerase activity may protect granulocyte RTL from significant shortening. The unexpected associations observed in mononuclear cell RTL emphasize the complex interplay between immune responses, cellular aging, and functional capacity in older adults.
Assuntos
Envelhecimento , Leucócitos , Masculino , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Encurtamento do Telômero , Telômero , Desempenho Físico FuncionalRESUMO
Telomeres and telomerase are closely linked to uncontrolled cellular proliferation, immortalization and carcinogenesis. Telomerase has been largely studied in the context of cancer, including leukemias. Deregulation of human telomerase gene hTERT is a well-established step in leukemia development. B-acute lymphoblastic leukemia (B-ALL) recovery rates exceed 90% in children; however, the relapse rate is around 20% among treated patients, and 10% of these are still incurable. This review highlights the biological and clinical relevance of telomerase for B-ALL and the implications of its canonical and non-canonical action on signaling pathways in the context of disease and treatment. The physiological role of telomerase in lymphocytes makes the study of its biomarker potential a great challenge. Nevertheless, many works have demonstrated that high telomerase activity or hTERT expression, as well as short telomeres, correlate with poor prognosis in B-ALL. Telomerase and related proteins have been proven to be promising pharmacological targets. Likewise, combined therapy with telomerase inhibitors may turn out to be an alternative strategy for B-ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Telomerase , Criança , Humanos , Telomerase/genética , Telomerase/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Encurtamento do Telômero , Telômero/genética , Telômero/metabolismoRESUMO
Bipolar Disorder (BD) has recently been related to a process of accelerated aging, with shortened leukocyte telomere length (LTL) in this population. It has also been observed that the suicide rate in BD patients is higher than in the general population, and more recently the telomere length variation has been described as shorter in suicide completers compared with control subjects. Objectives The aim of the present study was to investigate if there is an association between LTL and BD in families where two or more members have BD including clinical symptomatology variables, along with suicide behavior. Methods Telomere length and single copy gene ratio (T/S ratio) was measured using quantitative polymerase chain reaction in a sample of 143 relatives from 22 families, of which 60 had BD. The statistical analysis was performed with a polygenic mixed model. Results LTL was associated with suicidal ideation (p = 0.02) as that there is an interaction between suicidal ideation and course of the disorder (p = 0.02). The estimated heritability for LTL in these families was 0.68. In addition, covariates that relate to severity of disease, i.e. suicidal ideation and course of the disorder, showed an association with shorter LTL in BD patients. No difference in LTL between BD patients and healthy relatives was observed. Conclusion LTL are shorter in subjects with familial BD suggesting that stress related sub-phenotypes possibly accelerate the process of cellular aging and correlate with disease severity and suicidal ideation.
Assuntos
Transtorno Bipolar , Suicídio , Humanos , Transtorno Bipolar/genética , Ideação Suicida , Telômero/genética , Leucócitos , Encurtamento do Telômero/genéticaRESUMO
Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening. Objectives: The objective of the study was to study TL changes in patients at early disease onset and after follow-up. Methods: Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, self-compared after follow-up, and a reference group of sex- and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant. Results: The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2, 95%CI: 3.5-74.4; p < 0.0001). Conclusions: At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL.