Abstract

The aging process occurs due to the decline of physiological functions and the ability of the organism to adapt, being influenced by genetics and lifestyle. Currently, with advances in genetics, biological aging can be calculated by the telomere length (‘telomere lenght’). Telomeres are regions at the ends of chromosomes that play a role in the maintenance and integrity of DNA. With biological aging, telomere shortening occurs, causing cellular senescence. Numerous studies show that shorter telomeres are associated with chronic diseases, addictions and intoxications. On the other hand, healthy living habits promote the increase of telomere length and the balance of the different cellular functions, preventing diseases. Thus, telomeres function as a biomarker of the vitality of the organism. // Resumen: El proceso de envejecimiento se produce por la disminución de las funciones fisiológicas y de la capacidad de adaptación del organismo, siendo influenciado por la genética y el estilo de vida. Actualmente, con los avances de la genética, el envejecimiento biológico se puede calcular por la longitud de los telómeros (‘telomere lenght’). Los telómeros son regiones en los extremos de los cromosomas que juegan un papel en el mantenimiento y la integridad del ADN. Con el envejecimiento biológico, se produce el acortamiento de los telómeros, causando la senescencia celular. Numerosos estudios evidencian que telómeros más cortos están asociados a enfermedades crónicas, a vicios y a intoxicaciones. Por otro lado, hábitos de vida saludables propician el aumento de la longitud de los telómeros y el equilibrio de las diversas funciones celulares, previniendo enfermedades. Por lo tanto, los telómeros funcionan como un biomarcador de la vitalidad del organismo.
12 LA HOMEOPATÍA DE MÉXICO. Volumen 89, número 720, enero - marzo 2020, p. 12-17.
Marcus Zulian Teixeira
*Telómeros y Telomerasa:
Marcadores Biológico-Genómicos
de la Vitalidad-Actividad Celular, de
la Longevidad-Envejecimiento y del
Proceso Salud-Enfermedad
Resumen
El proceso de envejecimiento se produce por la disminución de las funciones siológicas y
de la capacidad de adaptación del organismo, siendo inuenciado por la genética y el estilo
de vida. Actualmente, con los avances de la genética, el envejecimiento biológico se puede
calcular por la longitud de los telómeros (‘telomere lenght’). Los telómeros son regiones en
los extremos de los cromosomas que juegan un papel en el mantenimiento y la integridad
del ADN. Con el envejecimiento biológico, se produce el acortamiento de los telómeros,
causando la senescencia celular. Numerosos estudios evidencian que telómeros más cortos
están asociados a enfermedades crónicas, a vicios y a intoxicaciones. Por otro lado, hábitos
de vida saludables propician el aumento de la longitud de los telómeros y el equilibrio de las
diversas funciones celulares, previniendo enfermedades. Por lo tanto, los telómeros funcio-
nan como un biomarcador de la vitalidad del organismo.
**Marcus Zulian Teixeira
*Publicado originalmente en el sitio “Ho-
meopatía: Ciencia, Filosofía y Arte de
Curar”. Dirección electrónica:
http://www.homeozulian.med.br
Traducción del inglés al español: Jesús
Navarro Hernández.
**Médico homeópata. Doctor y postdoc-
tor en Medicina por la Facultad de Me-
dicina de la Universidad de Sao Paulo
(FMUSP, Brasil). Coordinador de la ma-
teria optativa “Fundamentos de Homeo-
patía” de la FMUSP. Coordinador de lo
Departamento Científico de Homeopa-
tía de la Asociación de Medicina de Sao
Paulo (APM).
Artículo de revisión
PALABRAS CLAVE:
Telómeros, Telomerasa, Biomarcador, Envejecimiento, Senescencia, Enfermedades crónicas.
KEYWORDS:
Telomeres, Telomerase, Biomarker, Aging, Senescence, Chronic Diseases.
www.latindex.unam.mx periodica.unam.mx lilacs.bvsalud.org/es/ www.imbiomed.com
Abstract
The aging process occurs due to the decline of physiological functions and the ability of
the organism to adapt, being inuenced by genetics and lifestyle. Currently, with advances
in genetics, biological aging can be calculated by the telomere length (‘telomere lenght’).
Telomeres are regions at the ends of chromosomes that play a role in the maintenance
and integrity of DNA. With biological aging, telomere shortening occurs, causing cellular
senescence. Numerous studies show that shorter telomeres are associated with chronic
diseases, addictions and intoxications. On the other hand, healthy living habits promote the
increase of telomere length and the balance of the different cellular functions, preventing
diseases. Thus, telomeres function as a biomarker of the vitality of the organism.
13
LA HOMEOPATÍA DE MÉXICO. Volumen 89, número 720, enero - marzo 2020, p. 12-17.
Telómeros y Telomerasa: Marcadores Biológico-Genómicos de la Vitalidad-Actividad Celular, de la Longevidad-Envejecimiento y del Proceso Salud-Enfermedad
El proceso irreversible de envejecimiento está
marcado por una disminución de las funciones
siológicas y la capacidad de adaptación del
cuerpo, siendo fuertemente inuenciado por la gené-
tica, así como por factores ambientales y estilo de
vida. Actualmente, el proceso de envejecimiento se
divide en dos componentes principales, edad crono-
lógica y edad biológica, que pueden diferir para el
mismo indivíduo. El envejecimiento biológico puede
ser calculado por la longitud de los telómeros (TL o
‘telomere lenght’) y por los niveles de metilación del
ADN (epigenética)1-4.
Los telómeros son regiones no codicantes
del genoma, ubicadas en los extremos de los cro-
mosomas (capas protectoras de los cromosomas),
que consisten en largas series de secuencias cortas
y repetidas formadas por bases nitrogenadas 5’-TTA-
GGG-3’ y por proteínas asociadas, que desempeñan
un papel importante en el mantenimiento y la integri-
dad del ADN. El acortamiento de los telómeros puede
comprometer el potencial replicativo de las células,
contribuyendo a que ocurra el proceso natural de se-
nescencia celular. Para contrarrestar este proceso, la
enzima telomerasa promueve el mantenimiento de la
longitud de los telómeros al sintetizar las secuencias
repetitivas del ADN telomérico.
Durante la división o duplicación celular, las
células son incapaces de replicar aproximadamente
50 pares de bases nitrogenadas de los extremos de
los cromosomas, ya que la ADN polimerasa conven-
cional no puede reproducir el extremo 3’ de la molé-
cula lineal (“problema de la replicación nal”). Esto
conduce al acortamiento progresivo del cromosoma
a lo largo de las divisiones de una línea celular, resul-
tando en la pérdida de la capacidad replicativa y en la
inducción de la senescencia celular. Este mecanismo
es la principal causa de envejecimiento y de enfer-
medades crónicas relacionadas con la edad5-7.
Para evitar ese acortamiento progresivo de
los telómeros que ocurre a cada división celular y
la consecuente pérdida de la información genética,
periódicamente, los segmentos de ADN perdidos se
recuperan, gracias a un complejo enzimático ribonu-
cleoprotéico llamado telomerasa. Este complejo po-
see un pequeño componente de ARN que constituye
un molde para la síntesis de las secuencias repeti-
tivas que compone el telómero. En la recuperación
del ADN perdido, las bases nucleotídicas se agregan
individualmente y en la secuencia correcta, y la telo-
merasa progresa discontinuas, es decir, el molde de
ARN se coloca sobre el ADN iniciador, varios nucleó-
tidos se agregan al mismo y, después, la enzima se
traslada para comenzar el proceso de nuevo7-9.
En 2009, Elizabeth Blackburn, Carol Greider
y Jack Szostak recibieron el Premio Nobel de Fi-
siología o Medicina por descubrir el papel protector
de los telómeros y de la enzima telomerasa en los
cromosomas10-12. Estos descubrimientos, extrema-
damente signicativos, allanaron el camino para que
los investigadores exploraran aún más el papel del
acortamiento de los telómeros en el envejecimiento y
en las enfermedades crónicas, en general.
Numerosos estudios evidencian que los teló-
meros más cortos están asociados con una serie de
enfermedades crónicas tales como disceratosis con-
génita, anemia aplásica, brosis pulmonar idiopática
y cirrosis hepática13; enfermedades cardiovascula-
re15; diabetes mellitus tipo 216-18; aterosclerosis19; hi-
pertensión20; accidente cerebrovascular21; enferme-
dades autoinmunes: lupus sistémico eritematoso22 y
artritis reumatoide23; enfermedades psiquiátricas24; y
demencias25,26, entre otras enfermedades relaciona-
das con la edad27.
En el cáncer, el tamaño de los telómeros
tiene un doble papel: el acortamiento de los telóme-
ros puede conducir a la inducción de la inestabilidad
cromosómica y al inicio de la formación de tumores
(lesión pre-cancerosa); sin embargo, los tumores ini-
ciados necesitan reactivar la telomerasa para estabi-
lizar cromosomas y obtener capacidad de crecimien-
to inmortal28, 29.
El mismo acortamiento de los telómeros se
observa en otros trastornos crónicos de salud, vicios e
intoxicaciones, tales como: obesidad (alto IMC)30; proce-
sos inamatorios y oxidativos31; tabaquismo32; alcoholis-
mo33; dependencia de droga34; exposición a la contami-
nación y a las partículas minerales35-37, entre otras.
En niños sobrevivientes de cáncer, estudios
recientes evidencian la disminución del tamaño de
los telómeros asociada a trastornos crónicos de sa-
lud, como consecuencia del tratamiento recibido (ra-
dioterapia y quimioterapia)38; otros tratamientos y/o
medicamentos han demostrado el mismo efecto de
acortamiento de los telómeros (inmunosupresores,
inhibidores de las bombas de protones e insulina,
entre otros)39-41.
Además, trastornos psicoemocionales expe-
rimentados a lo largo de la vida (exposiciones socia-
les/traumáticas), tales como estrés crónico y adversi-
dades en la infancia (como abuso, violencia, racismo,
bulling, bajo nivel socioeconómico, depresión mater-
na, perturbación familiar e institucionalización), entre
otros, también causan disminución del tamaño de los
telómeros42-49.
14 LA HOMEOPATÍA DE MÉXICO. Volumen 89, número 720, enero - marzo 2020, p. 12-17.
Marcus Zulian Teixeira
Además del envejecimiento natural y crono-
lógico, el acortamiento de los telómeros puede estar
inuenciado por la actividad física, índice de masa
corporal (IMC), terapia de reposición hormonal, taba-
quismo, inamación crónica, estrés oxidativo, antio-
xidantes dietéticos y vitaminas. Estudios previos han
demostrado que los individuos que siguen un estilo
de vida saludable tienen telómeros más largos50.
La telomerasa está activa en las primeras
etapas del desarrollo humano (células embrionarias
pluripotentes) y, durante toda la vida, en células ma-
dre sanguíneas, germinales y de tejidos adultos en
renovación continua, como, por ejemplo, en el tejido
endometrial51. En el período neonatal, la actividad de
la enzima es reducida o nula, quedando ausente en
la mayoría de los tejidos somáticos del organismo.
Como consecuencia de ello, gradualmente, a cada
división celular los terminales teloméricos de estas
células se acortan, llegando a un límite mínimo de
tamaño que posibilite la división celular52.
Por otro lado, el 90% de las células somáti-
cas cancerígenas, que alcanzan la inmortalidad ce-
lular, presentan alta expresividad de la telomerasa
(telómeros largos). En estas células tumorales, la
reactivación del gen silenciado de la telomerasa ha
sido uno de los mecanismos utilizados para burlar el
sistema natural de senescencia celular y apoptosis,
permitiendo que estas células continúen promovien-
do el alargamiento de los telómeros y se repliquen de
manera descontrolada e ininterrumpida53,54.
Actuando como biomarcador de la vitalidad y
de la actividad celular, de la longevidad y del enveje-
cimiento, la medición de la longitud de los telómeros
de ADN de leucocitos extraídos de sangre periféri-
ca55 proporciona parámetros clínicos y dinámicos de
la salud y el bienestar, pudiendo ser utilizados como
método diagnóstico y pronóstico del proceso salud-
enfermedad56, pero también para medir la ecacia
y la efectividad de las diversas terapias empleadas,
tales como la Homeopatía57, la acupuntura58 y la me-
ditación59.
El conocimiento actual sobre los telómeros
y la telomerasa reitera la importancia que debe dedi-
carse al estilo de vida saludable y a las medidas pro-
motoras de la salud, tales como: actividad física regu-
lar, dieta equilibrada (suplementación con sustancias
antioxidantes), control del peso corporal, actividades
espirituales y contemplativas, prácticas integrativas y
complementarias en salud (Homeopatía, acupuntu-
ra, meditación, etcétera), entre otras, que propician el
aumento de la longitud de los telómeros y el equilibrio
de las diversas funciones celulares, previniendo en-
fermedades y otros trastornos somáticos y psíquicos.
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Exceptionally long-lived individuals (ELLI) who are the focus of many healthy longevity studies around the globe are now being studied in Israel. The Israeli Multi-Ethnic Centenarian Study (IMECS) cohort is utilized here for assessment of various DNA methylation clocks. Thorough phenotypic characterization and whole blood samples were obtained from ELLI, offspring of ELLI, and controls aged 53–87 with no familial exceptional longevity. DNA methylation was assessed using Illumina MethylationEPIC Beadchip and applied to DNAm age online tool for age and telomere length predictions. Relative telomere length was assessed using qPCR T/S (Telomere/Single copy gene) ratios. ELLI demonstrated juvenile performance in DNAm age clocks and overall methylation measurement, with preserved cognition and relative telomere length. Our findings suggest a favorable DNA methylation profile in ELLI enabling a slower rate of aging in those individuals in comparison to controls. It is possible that DNA methylation is a key modulator of the rate of aging and thus the ELLI DNAm profile promotes healthy longevity.
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There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer's disease and all-cause dementia in a population-based setting. Within the Rotterdam Study, we performed quantitative PCR to measure mean leukocyte telomere length in blood. We determined the association of telomere length with risk of Alzheimer's disease until 2016, using Cox regression models. Of 1,961 participants (mean age 71.4±9.3 years, 57.1% women) with a median follow-up of 8.3 years, 237 individuals were diagnosed with Alzheimer's disease. We found a U-shaped association between telomere length and risk of Alzheimer's disease: compared to the middle tertile the adjusted hazard ratio was 1.59 (95% confidence interval (CI), 1.13-2.23) for the lowest tertile and 1.47 (1.03-2.10) for the highest tertile. Results were similarly U-shaped but slightly attenuated for all-cause dementia. In conclusion, shorter and longer telomere length are both associated with an increased risk of Alzheimer's disease in the general population.
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Rationale Human telomeres consist of tandem repeats at chromosome ends which protect chromosomal DNA from degradation. Telomere shortening occurs as part of natural aging; however, life stressors, smoking, drug use, BMI, and psychiatric disorders could disrupt cell aging and affect telomere length (TL). In this context, studies have evaluated the effects of alcohol consumption on TL; however, results have been inconsistent, which may reflect diverse drinking cut-offs and categorizations. Objectives To help clarify this, the present study addresses the association of TL with alcohol use disorder (AUD), drinking behaviors, lifetime stress, and chronological age. Methods TL was quantified as the telomere to albumin ratio (T/S ratio) obtained from peripheral blood DNA using the quantitative PCR assay, from 260 participants with AUD and 449 non-dependent healthy controls (HC) from an existing National Institute on Alcohol Abuse and Alcoholism (NIAAA) database. Results AUD participants showed shorter TL compared to HC with both, age, and AUD, as independent predictors as well as a significant AUD with age interaction effect on TL. TL was also associated with impulsiveness in AUD participants. We did not observe an association between TL and chronicity of alcohol use, alcohol doses ingested, or childhood trauma exposures in either AUD or HC, although very few HC reported a history of childhood trauma. Conclusion Our results support previous findings of telomere shortening with chronic alcohol exposures and show both an effect of AUD on TL that is independent of age as well as a significant AUD by age interaction on TL. These findings are consistent with accelerated cellular aging in AUD.
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Objective: Telomeres are protective sequences of DNA capping the ends of chromosomes that shorten over time. Leukocyte telomere length (LTL) is posited to reflect the replicative history of cells and general systemic aging of the organism. Chronic stress exposure leads to accelerated LTL shortening, which has been linked to increased susceptibility to and faster progression of aging-related diseases. This study examined longitudinal associations between LTL and experiences of racial discrimination, a qualitatively unique source of minority psychosocial stress, among African Americans. Method: Data are from 391 African Americans in the Coronary Artery Risk Development in Young Adults (CARDIA) Telomere Ancillary Study. We examined the number of domains in which racial discrimination was experienced in relation to LTL collected in Years 15 and 25 (Y15: 2000/2001; Y25: 2010/2011). Multivariable linear regression examined if racial discrimination was associated with LTL. Latent change score analysis (LCS) examined changes in racial discrimination and LTL in relation to one another. Results: Controlling for racial discrimination at Y15, multivariable linear regression analyses indicated that racial discrimination at Y25 was significantly associated with LTL at Y25. This relationship remained robust after adjusting for LTL at Y15 (b = -.019, p = .015). Consistent with this finding, LCS revealed that increases in experiences of racial discrimination were associated with faster 10-year LTL shortening (b = -.019, p = .015). Conclusions: This study adds to evidence that racial discrimination contributes to accelerated physiologic weathering and health declines among African Americans through its impact on biological systems, including via its effects on telomere attrition. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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Objective: Telomeres are the caps at the end of chromosomes. Short telomeres are a biomarker for worsening health and early death. Design: The present study consolidated research on meditation and telomere length through a meta-analysis of results of studies examining the effect of meditation on telomere length by comparing the telomere length of meditating participants with participants in control conditions. Results: A search of the literature identified 11 studies reporting 12 comparisons of meditating individuals with individuals in control conditions. An overall significant weighted effect size of g =.40 indicated that the individuals in meditation conditions had longer telomeres. When an outlier effect size was trimmed from the analysis, the effect size was smaller, g =.16. Across studies, a greater number of hours of meditation among participants in meditation conditions was associated with larger effect sizes. Conclusion: These findings provide tentative support for the hypothesis that participants in meditation conditions have longer telomeres than participants in comparison conditions, and that a greater number of hours of meditation is associated with a greater impact on telomere biology. The results of the meta-analysis have potential clinical significance in that they suggest that meditation-based interventions may prevent telomere attrition or increase telomere length.
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Purpose of review: Telomere length has been hypothesized as a putative biomarker for cardiovascular disease. However, the findings are mixed and shared confounding factors may explain these associations. The current review aims to summarize the recent literature on the role of telomere length in cardiovascular disease and give directions for future potential as a predictive biomarker. Recent findings: In this review, we outline the biology of telomeres as a biomarker of aging through its shortening capacity across the life course. Recent epidemiological evidence for its associations with cardiovascular risk factors and disease is discussed. Then we highlight the possible causal role of telomeres in coronary heart disease and summarize the potential biological mechanisms and pathways known. Summary: The current research and results presented on telomere length may implicate that short telomeres are causal risk factors for cardiovascular disease, partially through insulin-mediated pathways. Nevertheless, further studies with refined quantification methods and larger populations are needed to clarify the added role of telomere length in predicting future risks of cardiovascular disease on top of existing risk biomarkers, and whether it may be amenable for intervention.
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Background: Stress exposure occurring across the lifespan increases risk for disease, potentially involving telomere length shortening. Stress exposure during childhood and adulthood has been cross-sectionally linked with shorter telomere length. However, few longitudinal studies have examined telomere length attrition over time, and none have investigated how stressor duration (acute life events vs. chronic difficulties), timing (childhood vs. adulthood), and perceived severity may be uniquely related to telomere length shortening. Methods: To address these issues, we administered a standardized instrument for assessing cumulative lifetime stress exposure (Stress and Adversity Inventory; STRAIN) to 175 mothers of children with Autism Spectrum Disorder or neurotypical children and measured their leukocyte telomere length (LTL) at baseline and 2 years later. Results: Greater count of lifetime stressors was associated with shorter LTL at baseline and greater LTL attrition over time. When separating lifetime stressors into acute life events and chronic difficulties, only greater count of chronic difficulties significantly predicted shorter baseline LTL and greater LTL attrition. Similarly, when examining timing of stressor exposure, only greater count of chronic childhood difficulties (age < 18) significantly predicted shorter baseline LTL and greater LTL attrition over the 2-year period in mid-life. Importantly, these results were robust while controlling for stressors occurring during the interim 2-year period. Post-hoc analyses suggested that chronic difficulties occurring during earlier childhood (0-12 years) were associated with greater LTL attrition. Cumulative stressor severity predicted LTL attrition in a parallel manner, but was less consistently associated with baseline LTL. Conclusions: These data are the first to examine the effects of different aspects of cumulative lifetime stress exposure on LTL attrition over time, suggesting that accumulated chronic difficulties during childhood may play a unique role in shaping telomere shortening in midlife.