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diff --git a/gnqa/paper1_eval/src/data/responses/general/gen_resp07.json b/gnqa/paper1_eval/src/data/responses/general/gen_resp07.json new file mode 100644 index 0000000..01cb1c3 --- /dev/null +++ b/gnqa/paper1_eval/src/data/responses/general/gen_resp07.json @@ -0,0 +1,134 @@ +{ + "created_at": "2024-04-01T12:07:20.647660Z", + "data": { + "amplify": false, + "answer": "The length of telomeres is significant as it is associated with aging, disease, and mortality. Longer telomeres are generally associated with better health outcomes, including protection from age-related diseases, better cognitive function, and healthier lipid profiles. Shorter telomeres, on the other hand, have been linked to higher risks of heart disease, infection-related death, and other diseases. Telomere length can also be influenced by factors such as stress, with high-stress situations potentially leading to faster telomere shortening and premature aging.", + "context": { + "1ac23aae-2a51-4846-81ec-6db70ab6e5a4": [ + { + "document_id": "1ac23aae-2a51-4846-81ec-6db70ab6e5a4", + "text": "\n\nIn birds, where erythrocyte telomere length (ETL) is measured, the majority of species sampled have shown no sex difference (36).Nonetheless, bird telomere dynamics are complex and, as with humans, may be affected by environment and stress.For example, a longitudinal study of black-tailed gulls (Larus crassitostris) over 2-5 years found no correlation between ETL and age or sex.Rather, ETL attrition was correlated with reduced food availability and environmental stressors (55).In a captive zebra finch (Taeniopygia guttata) population, male and female mean telomere length decreased with increasing age of the animals, but did differ between sexes (56).As these examples illustrate, the relationship between telomere length, lifespan, and sex is likely to be complex in other vertebrates." + }, + { + "document_id": "1ac23aae-2a51-4846-81ec-6db70ab6e5a4", + "text": "\n\nComparative studies of age-related telomere attrition in other species also reveal a variety of patterns.Barrett and Richardson (36) recently summarized the comparative data available on sex differences in telomere length.They found a strong correlation between male-biased mortality and either shorter telomeres or greater telomere attrition in males across bird and mammal taxa.However, telomere length did not differ between males and females in species where females are shorter-lived than males (36), suggesting that telomere shortening is not associated with species-specific longevity in a simple linear fashion.These studies generally suffer from relatively small sample sizes and are largely cross-sectional.Further, the use of diverse assays, different tissues (eg, leukocytes in mammals vs erythrocytes in birds), and lack of standardized benchmarks for accuracy makes comparisons between studies difficult." + }, + { + "document_id": "1ac23aae-2a51-4846-81ec-6db70ab6e5a4", + "text": "\n\nIn some organisms, there is no clear relationship between telomere length and lifespan.Age-related telomere attrition could not be detected in Daphnia pulex (57) or sea urchin species (Strongylocentrotus franciscanus and Lytechinus variegatus) (58).Studies in C. elegans examining natural variation in telomere length and experimentally manipulated telomere length detect no correlation with lifespan (59,60), and in Drosophila, which uses a telomerase-independent mechanism for telomere maintenance, there is a similar lack of correlation between longevity and telomere length (61).Similarly, data on sex differences in age-related telomere shortening are mixed.For example, in the ant species Lasius niger, the rate of telomere shortening is more rapid in short-lived males compared to longer-lived females.But, mean telomere length does not differ between the two types of females, queens and workers, despite the fact that queens live much longer than workers (up to 28 years vs 2-3 months) (62).These findings suggest that the question of how telomere shortening affects aging across species and how sex affects telomere attrition rates are complex." + } + ], + "5a8540de-d034-4dc4-b08b-e96e22f47ff8": [ + { + "document_id": "5a8540de-d034-4dc4-b08b-e96e22f47ff8", + "text": "\n\nWith new methodologies to assess relative telomere length by Q-PCR, studies were designed to address the impact of telomere length on aging, aging associated pathologies, and mortality.One such study has correlated shorter leukocyte telomere lengths at age 60 with a three times higher risk of heart disease and an eightfold increase in risk of infection-related death (36), thereby associating measured relative cellular aging with disease and life expectancy.In a similar way, chronic stress was shown to correlate with short leukocyte telomere length, a phenomenon attributed to higher levels of oxidative stress at the cellular level (70).More recent studies have linked telomere length in smooth muscle cells with senescence and disease severity in patients with atherosclerosis (141,150).Leukocyte telomere length was also short in a cohort of similar patients and associated with a higher risk of developing occult cardiovascular disease (71).More data are needed to understand and validate the use of leukocyte telomere length as a biomarker for cardiovascular and other diseases." + } + ], + "5e6ad994-9cad-4b8b-903d-2d5c350e25dc": [ + { + "document_id": "5e6ad994-9cad-4b8b-903d-2d5c350e25dc", + "text": "\n\nShortening of the telomeres at the ends of chromosomes has been associated with age-related disease and mortality [16][17][18].A recent study identified a common haplotype of four SNPs in the human telomerase reverse transcriptase gene (hTERT) that is enriched in centenarians and associated with longer telomere length [19].It was also shown that centenarians and their offspring maintain longer telomeres compared with controls and that longer telomeres are associated with protection from age-related diseases, better cognitive function and lipid profiles of healthy ageing [19]." + } + ], + "99445b90-1950-4299-815d-e912c5ae06ac": [ + { + "document_id": "99445b90-1950-4299-815d-e912c5ae06ac", + "text": "\n\nNew research has indicated how social factors, such as subordination, may translate into biological effects (epel et al. 2004;Chae et al. 2014).In a now classic study, epel et al. ( 2004) examined the telomere lengths of fifty-eight healthy premenopausal women who either had a healthy child (n = 19) or were giving care to a chronically ill child (n = 39. )They measured perceived stress, years of caregiving, telomere length, and oxidative stress.They found highly statistically significant differences in telomere length between women taking care of chronically ill children and those who had healthy children.They found highly statistically significant negative correlations between telomere length and perceived stress and years of caregiving.Telomerase activity had highly statistically significant negative correlations with perceived stress and years of caregiving.Oxidative stress was highly positively correlated with perceived stress and years of caregiving.They concluded that the telomere length shortening was equivalent to 9 to 17 years of aging in the high stress group.Telomere length is considered a biomarker of aging (Finch and Kirkwood 2000).Thus, this study showed that caregiver stress had essentially aged these women 9 to 17 years compared to women who had healthy children." + } + ], + "c9fda811-1e12-480c-b432-987fa1d24fce": [ + { + "document_id": "c9fda811-1e12-480c-b432-987fa1d24fce", + "text": "\n\nThe single, consistent predictor of the rate of telomere attrition shown in multiple adult and the few child longitudinal studies is the baseline measurement of telomere length at the start of each study.This suggests the importance of understanding predictors of telomere length prior to adulthood, as it determines in part the rate of change (Revesz et al. 2014a, b;Nordfjall et al. 2009).Moreover, longitudinal studies in adults have had found that telomere attrition rate is dependent on baseline telomere length independent of any phenotypic predictors of shortening, such as disease or demographic variables (Nordfjall et al. 2009), attesting to the importance of studies to evaluate risk factors for shortening prior to adulthood." + }, + { + "document_id": "c9fda811-1e12-480c-b432-987fa1d24fce", + "text": "\n\nRates of decline in childhood may be particularly relevant for later chronic disease risk as shorter telomere length has been implicated in disease progression through exposure to cellular senescence, inflammatory cytokines and adipocyte hypertrophy (Raschenberger et al. 2015;Willeit et al. 2014;Monickaraj et al. 2012;Fyhrquist et al. 2013)." + }, + { + "document_id": "c9fda811-1e12-480c-b432-987fa1d24fce", + "text": "\n\nAdult studies have also found a negative correlation with baseline telomere length, suggesting a negative feedback regulation of leukocyte telomere length (Farzaneh-Far et al. 2010;Aviv et al. 2009;Epel et al. 2008;Nordfjall et al. 2009).It is possible that while our follow-up period was shorter than Shalev et al. 2013 and adult studies, which had a minimum of 5 year intervals with the exception of Puterman et al. (2015) who followed for a one-year time period, there may be biological regulation of telomere length at 4 and 5 years of age such that shorter telomeres are more robustly maintained, whereas longer telomeres have greater rates of decline, over a short period of one year.It is unlikely that this relationship is due to assay error or regression to the mean given the consistency of our findings across studies.We have had similar findings of longer telomeres having greater rates of decline and shorter telomeres being maintained in our different studies (Farzaneh-Far et al. 2010;Epel et al. 2008;Puterman et al. 2015)." + }, + { + "document_id": "c9fda811-1e12-480c-b432-987fa1d24fce", + "text": "\n\nWe found primarily maintenance and lengthening from 4 to 5 years of age in children, with minimal telomere attrition, indicating that most of the telomere loss happens in the first 4 years, plateauing by age 4. Lastly, we found close to 10 % of the variance in rate of change in children shared by mothers.While some of this shared variance is genetic, there are likely environmental factors that need to be further identified that impact rate of telomere length change." + }, + { + "document_id": "c9fda811-1e12-480c-b432-987fa1d24fce", + "text": "\n\nAbstract Telomeres are the protective complexes at the end of chromosomes, required for genomic stability.Little is known about predictors of attrition in young children or the relationship between parental and child patterns of telomere change.Telomere length was assessed twice over one year, at 4 and at 5 years of age, in Latino preschool children (n = 77) and their mothers (n = 70) in whole blood leukocytes.Maternal and child rates of attrition during the same time period were compared in 70 mother-child pairs.More children showed lengthened telomeres over one year compared to their mothers and very few children showed attrition (2.6 %).Approximately 31 % of children and 16 % of mothers displayed lengthening over one year while 66 % of children showed maintenance in contrast with 74 % of mothers.The strongest predictor for child telomere length change was child's baseline telomere length (r = −0.61,p < 0.01).Maternal rate of change was associated with child rate of change (r = 0.33, p < 0.01).After controlling for child baseline telomere length, the relationship between child and maternal rate of change trended towards significance (Coeff = 0.20, 95 % CI −0.03 to 0.43; p = 0.08)." + } + ], + "ca76f85d-9f72-4e15-8ba9-3bf94308c449": [ + { + "document_id": "ca76f85d-9f72-4e15-8ba9-3bf94308c449", + "text": "\n\nBlackburn and Epel, a health psychologist who did original research on how specific lifestyle and psychological habits can protect telomeres, published The Telomere Effect (Blackburn & Epel, 2017), in which they suggested that individuals with shorter telomeres developed diseases earlier in life (a shorter \"disease span\").What follows is the evidence from these authors, their colleagues, and other researchers describing how length of telomeres contributes to mind-body connection and healthy longevity." + } + ], + "eea4020b-1e14-4af9-9d67-f75d1802fdcd": [ + { + "document_id": "eea4020b-1e14-4af9-9d67-f75d1802fdcd", + "text": "\n\nAs early as at the time of birth, each of the 92 telomeres of the human genome has its own characteristic length.Additionally, each telomere shortens by its individual attrition rate.In general, longer telomeres at birth are associated with higher age-dependent attrition rates and vice versa.Overall, telomere shortening appears more dynamic in males." + }, + { + "document_id": "eea4020b-1e14-4af9-9d67-f75d1802fdcd", + "text": "\n\nIn conclusion, a combination of overall and chromosomespecifi c shorter telomeres and more pronounced age-dependent telomere erosion could be observed in males.There is a prospective clinical study strongly suggesting that longer telomeres decrease the risk of dying (Cawthon et al., 2003).With this in mind, the telomere length discrepancies between the sexes may indeed be a factor infl uencing the differences in their life expectancy." + }, + { + "document_id": "eea4020b-1e14-4af9-9d67-f75d1802fdcd", + "text": "\n\nIn every chromosome a linear decline of telomere length with age was observed, being more pronounced in men independent of the examined chromosome arm.This might suggest that telomere length on single chromosome arms may be infl uenced by the same factors which determine overall telomere length." + }, + { + "document_id": "eea4020b-1e14-4af9-9d67-f75d1802fdcd", + "text": "\n\nS. Mayer a S. Brüderlein a S. Perner a I. Waibel a A. Holdenried a N. Ciloglu a C. Hasel a T. Mattfeldt a K.V. Nielsen b P. Möller a a Institute of Pathology, University of Ulm, Ulm (Germany); b DakoCytomation A/S, Glostrup (Denmark) follow uniformity.In previous studies, sex-specifi c differences in telomere length and attrition rate of men and women were found (Benetos et al., 2001;Cawthon et al., 2003;Nawrot et al., 2004), suggesting gender differences in behavior of telomeres.In individual chromosome arms, telomere length was also shown not to be homogeneous (Lansdorp et al., 1996;Benn, 1997;Martens et al., 1998;Surralles et al., 1999;Hao and Tan, 2001;Londono-Vallejo et al., 2001;Graakjaer et al., 2003), some telomeres being signifi cantly shorter, others longer than the average length." + }, + { + "document_id": "eea4020b-1e14-4af9-9d67-f75d1802fdcd", + "text": "\n\nTo date, these characteristics in telomere lengths could not be set in a biological context, as only a few groups have provided detailed information about chromosome-specifi c patterns of telomere distribution (Lansdorp et al., 1996;Graakjaer et al., 2003).Whether accumulation of short telomeres (Martens et al., 2000;Londono-Vallejo et al., 2001) or rather the shortest telomere of one specifi c chromosome arm (Hemann et al., 2001) elicits senescence, remains an open question so far." + }, + { + "document_id": "eea4020b-1e14-4af9-9d67-f75d1802fdcd", + "text": "\n\nIn recent literature, there are hints that the average telomere length may be higher in women and that their annual shortening rate may be somewhat lower (Vaziri et al., 1993;Rufer et al., 1998;Jeanclos et al., 2000), but these reported differences failed to reach statistical signifi cance except for one study (Jeanclos et al., 2000).Here, we provide compelling evidence that this is indeed the case." + }, + { + "document_id": "eea4020b-1e14-4af9-9d67-f75d1802fdcd", + "text": "\n\nIt is generally accepted that telomeres shorten during DNA replication both in vitro and in vivo.In individuals, short telomeres are considered to be a sign of advanced age.Cawthon and coworkers (2003) showed that telomere shortening in humans likely contributes to mortality, supporting the hypothesis that they might act as a mitotic clock (Allsopp et al., 1992).Telomere length dynamics, however, does not seem to Abstract.During aging, telomeres are gradually shortened, eventually leading to cellular senescence.By T/C-FISH (telomere/centromere-FISH), we investigated human telomere length differences on single chromosome arms of 205 individuals in different age groups and sexes.For all chromosome arms, we found a linear correlation between telomere length and donor age.Generally, males had shorter telomeres and higher attrition rates.Every chromosome arm had its individual age-specifi c telomere length and erosion pattern, resulting in an unexpected heterogeneity in chromosomespecifi c regression lines.This differential erosion pattern, however, does not seem to be accidental, since we found a correlation between average telomere length of single chromosome arms in newborns and their annual attrition rate.Apart from the above-mentioned sex-specifi c discrepancies, chromosome arm-specifi c telomere lengths were strikingly similar in men and women.This implies a mechanism that arm specifi cally regulates the telomere length independent of gender, thus leading to interchromosomal telomere variations." + } + ], + "f3610ccc-2831-42f6-a3d3-1a0feeba4902": [ + { + "document_id": "f3610ccc-2831-42f6-a3d3-1a0feeba4902", + "text": "\n\nShortening of the telomeres at the ends of chromosomes has been associated with age-related disease and mortality [16][17][18].A recent study identified a common haplotype of four SNPs in the human telomerase reverse transcriptase gene (hTERT) that is enriched in centenarians and associated with longer telomere length [19].It was also shown that centenarians and their offspring maintain longer telomeres compared with controls and that longer telomeres are associated with protection from age-related diseases, better cognitive function and lipid profiles of healthy ageing [19]." + } + ] + }, + "data_source": [], + "document_id": "F91D61921F6212793795027C274D0E7E", + "engine": "gpt-4", + "first_load": false, + "focus": "api", + "keywords": [ + "telomeres", + "telomere&length", + "DNA", + "chromosomes", + "aging", + "senescence", + "leukocyte", + "telomerase", + "oxidative&stress", + "centenarians" + ], + "metadata": [], + "question": "What is the significance of the length of telomeres?", + "subquestions": null, + "task_id": "F91D61921F6212793795027C274D0E7E", + "usage": { + "chatgpt": 7797, + "gpt-4": 4400, + "gpt-4-turbo-preview": 3459 + }, + "user_id": 2 + }, + "document_id": "F91D61921F6212793795027C274D0E7E", + "task_id": "F91D61921F6212793795027C274D0E7E" +} |