- Research article
- Open Access
- Published: 16 January 2023
BMC Medicine volume 21, Article number: 20 (2023) Cite this article
Abstract
Background
Visit-to-visit assemblage value variability (BWV), pulse complaint variability (PRV), and humor unit variability (BPV) person been respectively linked to aggregate wellness outcomes. The associations of the operation of semipermanent variability successful physiological measures with mortality and epigenetic property acceleration (EAA) stay mostly unknown.
Methods
We constructed a composite people of physiological variability (0-3) of ample variability successful BWV, PRV, and BPV (the apical tertiles) successful 2006/2008–2014/2016 successful the Health and Retirement Study (HRS) and 2011–2015 successful the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was documented done 2018. EAA was calculated utilizing thirteen DNA methylation-based epigenetic clocks among 1047 participants successful a substudy of the HRS. We assessed the narration of the composite people to the hazard of mortality among 6566 participants successful the HRS and 6906 participants successful the CHARLS by Cox proportional models and past investigated its relation with EAA utilizing linear regression models.
Results
A higher people of variability was associated with higher mortality hazard successful some cohorts (pooled hazard ratio [HR] per one-point increment, 1.27; 95% assurance interval [CI], 1.18, 1.39; P-heterogeneity = 0.344), aft accommodation for aggregate confounders and baseline physiological measures. Specifically, each SD increment successful BWV, PRV, and BPV was related to 21% (95% CI: 15%, 28%), 6% (0%, 13%), and 12% (4%, 19%) higher hazard of mortality, respectively. The composite people was importantly related to EAA successful second-generation clocks trained connected wellness outcomes (e.g., standardized coefficient = 0.126 successful the Levine clock, 95% CI: 0.055, 0.196) but not successful astir first-generation clocks trained connected chronological age.
Conclusions
Larger variability successful physiological measures was associated with a higher hazard of mortality and faster EAA.
Background
Global colonisation aging forecasts an expanding load of illness and disablement connected nationalist wellness [1,2,3]. Aging is viewed arsenic a gradual and progressive deterioration successful the integrity of biologic systems and tin beryllium indicated by molecular- and cellular-level changes [4]. Specifically, the nonaccomplishment of quality successful homeostasis attraction is simply a cardinal diagnostic of biologic aging [5], perchance done the hypothalamus-related regulatory axes [6].
Older adults thin to person fluctuating physiological measures [7, 8], and erstwhile studies person linked the semipermanent variabilities successful these measures to consequent hazard of aggregate aging-related wellness outcomes, including frailty [9, 10], cardiovascular diseases [11, 12], dementia [13,14,15], and mortality [16]. For example, a meta-analysis [16] showed that each SD increment successful BPV was associated with a 15% higher hazard of all-cause mortality. However, the wide associations of semipermanent variabilities successful large physiological measures with aging remained unclear. First, astir erstwhile studies focused connected 1 circumstantial benignant of physiological measure, portion aging is often accompanied by homeostatic imbalances successful aggregate systems [4], and the combined narration of these variability measures to mortality warrants probe crossed populations. Second, astir erstwhile studies utilized comparatively short-term measurements of physiological measures, and the narration of semipermanent variability successful physiological measures with mortality has been little explored. Moreover, the underlying mechanics remained unclear. Although epigenetic clocks person been suggested to seizure the complexity betwixt aging and homeostasis attraction [17] and bespeak biologic aging [18,19,20,21], fewer studies person examined their associations with variabilities successful physiological measures.
Therefore, we hypothesize that the semipermanent variability successful aggregate physiological measures could beryllium linked to accelerated aging. To measure the narration of the operation of BWV, PRV, and BPV with mortality and epigenetic accelerated aging (EAA), we leveraged 2 nationally typical prospective studies, the Health and Retirement Study (HRS) in the USA and the China Health and Retirement Longitudinal Study (CHARLS). In addition, the HRS 2016 Venous Blood Study (VBS) provided a unsocial accidental to analyse a sheet of well-constructed epigenetic clocks based connected high-quality DNA methylation information [22].
Methods
Study plan and population
This survey was based connected the Health and Retirement Study (HRS) [23] and the China Health and Retirement Longitudinal Study (CHARLS) [24], 2 nationalist cohort studies with akin designs [25, 26].
In the HRS, participants aged 50 oregon older were recruited and revisited biennially for postulation of sociodemographic, lifestyle, and objective information. Half of a randomly selected illustration received carnal examinations successful 2006, 2010, and 2014 and the different fractional successful 2008, 2012, and 2016 [25]. DNA methylation assays were conducted successful a typical subsample of the HRS 2016 Venous Blood Study (VBS) with comparable distributions of age, sex, education, and race/ethnicity to the full HRS 2016 illustration calved earlier 1960 [27]. For example, the HRS 2016 illustration had a mean property of 69.0 years and 59.3% female, and the corresponding values were 68.7 years and 58.0% successful the VBS. The HRS was approved by the Health Sciences and Behavioral Sciences Institutional Review Board astatine the University of Michigan (HUM00061128).
The CHARLS recruited participants aged 45 years oregon older successful 2011 and revisited them successful 2013, 2015, and 2018. Face-to-face interviews and carnal examinations were administered to each participants astatine each wave. The CHARLS was approved by the Ethics Committee of Pecking University (00001052-11, 014).
We conducted 2 superior analyses (Fig. 1 and Additional record 1: Fig. S1). First, we assessed the relations of a composite people of variability successful physiological measures to mortality, including 6566 HRS participants and 6906 CHARLS participants who (1) received 3 measurements of assemblage wide scale (BMI), pulse rate, and humor unit successful 2006–2016 (HRS) oregon 2011–2015 (CHARLS) and (2) were followed up to the adjacent question oregon had decease accusation during follow-up. Among the HRS-VBS participants who had high-quality DNA methylation information successful 2016 (N = 1047), we investigated the relation betwixt the composite people and EAA.
Study design. BWV, assemblage value variability; PRV, pulse complaint variability; BPV, humor unit variability; BMI, assemblage wide index
Variability successful assemblage weight, pulse rate, humor pressure, and composite score
Body weight, height, pulse rate, and humor unit successful the HRS (2006–2014 oregon 2008–2016) and the CHARLS (2011–2015) were measured pursuing akin protocols. Body value was measured utilizing an physics weighing standard without shoes and with airy clothing, and tallness was measured by having the responsive basal against a partition without shoes [28, 29]. BMI was calculated arsenic value successful kilograms divided by tallness successful meters squared. Pulse complaint and humor unit were each assessed 3 times, 45 to 60 s apart, respectively, successful a seated position, by trained interviewers utilizing an automated sphygmomanometer [28, 30]. The mean values of the past 2 valid measurements were utilized astatine each wave.
Visit-to-visit BWV, PRV, and BPV were calculated arsenic the coefficients of saltation (CV), i.e., quotient of modular deviation (SD) and mean, of BMI, pulse rate, and systolic humor unit (SBP), respectively. We utilized systolic humor unit variability (SBPV) to correspond BPV due to the fact that it had stronger associations with adverse wellness outcomes than diastolic humor unit (DBP) [31, 32]. We besides utilized DBPV arsenic an alternate BPV measurement successful the sensitivity analysis.
To bespeak the wide variability successful physiological measures, we constructed a composite people pursuing the strategy of a anterior survey [33]. The highest tertiles of BWV, PRV, and BPV were each assigned 1 point, and the mediate and lowest tertiles were assigned 0 point. We took the sum of the 3 binary indicators arsenic the composite people (range: 0–3), and a higher people represented greater intraindividual instability successful the physiological measures.
Ascertainment of mortality
All-cause mortality was documented from the latest physiological measurements (2014 oregon 2016 successful HRS and 2015 successful CHARLS) to the extremity of follow-up (2018). The HRS and CHARLS adopted akin strategies to place deaths utilizing information linkage from the colonisation registry and done interviews with informants oregon knowledgeable others [34, 35].
Epigenetic timepiece and epigenetic property acceleration
In the HRS-VBS, DNA methylation was assayed utilizing the Infinium Methylation EPIC BeadChip that covered implicit 850,000 CpG sites (test-retest reliability correlation > 0.97 for each CpG sites) [36]. Thirteen epigenetic clocks were constructed based connected DNA methylation data. Nine first-generation clocks (Horvath 1, Hannum, Horvath 2, Lin, Weidner, VidalBralo, Yang, Bocklandt, and Garagnani) were trained connected chronological age, and 4 second-generation clocks (Levine, Zhang, GrimAge, and DunedinPoAm38) were trained connected health-related outcomes [22, 37]. The thirteen epigenetic clocks [38,39,40,41,42,43,44,45,46,47,48,49,50] combined accusation for a fig of CpGs (typically 100–500) to nutrient indicators of epigenetic aging. For example, Horvath 1 utilized 353 CpGs selected by the elastic nett regression exemplary [38]. Missing beta methylation values were imputed with the mean worth of the fixed probe crossed each samples [36]. More accusation tin beryllium recovered successful the HRS-VBS protocol [36].
We defined EAA pursuing the strategy successful a erstwhile survey successful the HRS-VBS [22]: each timepiece worth was regressed connected chronological property successful 2016 and the standardized residual reflected EAA. A larger worth of the standardized residual indicated faster biologic aging erstwhile the chronological property was fixed [51].
Other covariates
In HRS and CHARLS, demographic, lifestyle, and objective factors were collected utilizing questionnaires astatine baseline, including age, sex defined by self-identity, acquisition level (high schoolhouse grade level, yes/no), marital presumption (married oregon not), smoking presumption (never/former/current), intoxicant depletion (never/former/current), household income (in quartiles for HRS and < 9999 yuan/≥ 10,000 yuan/missing for CHARLS), carnal enactment engagement (> 1 clip per week/1–3 times per month/never for HRS and any/never/missing for CHARLS), and self-reported diabetes mellitus, bosom disease, and stroke. In the HRS, contention (white/black/others) was self-reported. In the CHARLS, residence (rural/urban) was identified from the registry.
Statistical analyses
Baseline characteristics of the 6566 HRS participants, 6906 CHARLS participants, and 1047 HRS-VBS participants were presented successful mean ± modular deviation (SD) for continuous variables and fig (percentage) for categorical variables.
In the superior analyses, we assessed the relation betwixt the composite people of variability successful physiological measures and risk of mortality utilizing Cox proportional hazard models. Person-time was calculated from the latest physiological measurement to the twelvemonth of decease oregon the extremity of follow-up, whichever came first. We sequentially adjusted the hazard ratios (HRs) and 95% assurance intervals (CIs) for baseline age, gender, contention (for HRS only), residence (for CHARLS only), acquisition level, household income, marital status, smoking status, intoxicant consumption, carnal enactment engagement, baseline BMI, baseline pulse rate, and baseline humor pressure. The estimates from the two cohorts were pooled utilizing fixed-effect models erstwhile nary important heterogeneity was detected. Missing values for each continuous covariates (< 2%) were imputed by means and categorical variables by the astir populated categories, but for household income and carnal enactment engagement successful the CHARLS (using a missing category). We utilized linear regression models to measure the associations betwixt the composite people and EAA indicated by the 13 epigenetic clocks successful the HRS. Linear inclination was tested by assigning the median worth of each class and including it arsenic a continuous adaptable successful the models. To code multiplicity, we adjusted the P-values utilizing the Benjamini-Hochberg (B-H) methods successful the investigation of the composite people and EAA [52].
In the secondary analysis, we assessed the idiosyncratic associations of BWV, PRV, and BPV with mortality and EAA, respectively. The accommodation was the aforesaid arsenic the superior analysis, and baseline BMI, baseline pulse rate, and baseline humor unit were separately adjusted for the corresponding exposures.
We performed aggregate sensitivity analyses by (1) adjusting the models for baseline wellness conditions (diabetes mellitus, bosom disease, and stroke); (2) alternatively utilizing modular deviation (SD) and saltation autarkic of the mean (VIM) to correspond BWV, PRV, and BPV; (3) utilizing DBPV successful spot of SBPV; (4) constructing the composite people utilizing the medians of BWV, PRV, and BPV arsenic cutoffs alternatively than the apical tertiles; (5) alternatively assigning 0, 1, and 2 to the expanding tertiles of variability indicators to conception a caller composite people ranging from 0 to 6 and repeated the superior analysis; and (6) adjusting the models for cell-type proportions (the percentages of neutrophil, basophilic granulocyte, eosinophilic granulocyte, mononuclear granulocyte, and leukomonocyte successful the full number of achromatic humor cells) successful the investigation of EAA [53, 54].
Statistical analyses were performed utilizing R 4.1.0. We reported two-sided P values and 95% assurance intervals (CIs) throughout, and tests with P < 0.05 were considered statistically significant.
Results
Participant characteristics astatine baseline
Baseline characteristics of the survey colonisation successful the HRS cohort (N = 6566), HRS-VBS (N = 1047), and CHARLS (N = 6906) were presented successful Table 1. Compared with HRS participants, adults successful the CHARLS were younger (62.5 years vs. 73.0 years), less successful females (54.2% vs. 60.7%), little educated, much apt to be current smokers, little apt to be current alcohol consumers, and had smaller BWV, PRV, and BPV. Among the 1047 HRS-VBS participants, 59.6% were female, and 87.3% were White/Caucasian. The mean (SD) property of the HRS-VBS participants was 77.0 (5.5) years old, and the means of semipermanent BWV, PRV, and BPV were 4.9%, 9.0%, and 9.3%, respectively. Descriptive statistic of the 13 epigenetic clocks and EAA were displayed successful Additional record 1: Table S1.
Associations betwixt the composite people of variability and mortality and epigenetic property acceleration
A full of 778 participants died during follow-up, including 483 of the 6566 HRS participants (20,496 person-years) and 295 of the 6906 CHARLS participants (20,681 person-years). The relation betwixt the composite people of variability successful physiological measures and mortality was observed successful some cohorts (Fig. 2). Adjusted for aggregate confounders and baseline levels of these physiological measures, each constituent increment of the composite people was related to a 27% (95% CI: 18%, 39%, P-heterogeneity = 0.344) higher hazard of mortality. The corresponding HRs (95% CIs) were 1.32 (1.19, 1.46) successful the HRS and 1.22 (1.07, 1.38) successful the CHARLS. Compared with a variability people of 0, a people of 3 (co-existence of ample BWV, PRV, and BPV) was associated with the highest hazard of mortality (HR = 2.66, 95% CI: 1.93, 3.69 successful the HRS and HR = 1.93, 95% CI: 1.24, 3.02 successful the CHARLS). Detailed results could beryllium recovered successful Additional record 1: Table S2.
Multivariable adjusted hazard ratios (HRs) and 95% assurance intervals (CIs) of mortality associated with the composite people of variability successful the HRS and CHARLS. HRS, Health and Retirement Study; CHARLS, China Health and Retirement Longitudinal Study; HR, hazard ratio; CI, assurance interval. Models were adjusted for property (continuous), sex (female/male), acquisition (high schoolhouse grade level, yes/no), matrimony presumption (yes/no), residence (rural/urban) successful the CHARLS, contention (White/Black/others) successful the HRS, drinking presumption (current/ever/never), smoking presumption (current/ever/never), carnal enactment (> 1 clip per week/1–3 times per month/never successful the HRS and any/never/missing successful the CHARLS), household income (quartiles successful the HRS and ≤ 9999 yuan/≥ 10,000 yuan/missing successful the CHARLS), assemblage wide index, systolic humor pressure, and pulse complaint (all continuous) successful 2014/2016 (HRS) oregon successful 2015 (CHARLS). Fixed effect exemplary was utilized to excavation the results
Also, a greater composite people of variability was associated with faster EAA (z-score of the regression residual of the epigenetic timepiece connected chronological age) successful 4 second-generation clocks trained connected wellness outcomes, and the associations were consistently observed successful both male and pistillate participants (Fig. 3). Each constituent increment successful the people was related to faster EAA by 0.126 z-score (95% CI: 0.055, 0.196) successful the Levine clock, 0.094 z-score (95% CI: 0.028, 0.160) successful the Zhang clock, 0.096 z-score (95% CI: 0.040, 0.153) successful the GrimAge clock, and 0.074 z-score (95% CI: 0.009, 0.139) successful DunedinPoAm38. All tests were important aft B-H adjustments (adjusted P-values < 0.05) but for that of DunedinPoAm38 (adjusted P-value = 0.068). The relations were non-significant successful astir first-generation clocks that are trained connected chronological age, though the absorption was similar. For example, the standardized coefficient (95% CI) was 0.051 (− 0.020, 0.122) for the Horvath 1 clock. Details were displayed successful Additional record 1: Table S3.
Multivariable adjusted differences and 95% assurance intervals (CIs) successful epigenetic property acceleration indicated by second-generation clocks associated with the composite people of variability successful the wide colonisation and by gender. EAA, epigenetic property acceleration. β-Coefficients were derived from models adjusted for property (continuous), sex (female oregon male, unless successful gender-stratified analyses), acquisition (high schoolhouse grade level, yes/no), matrimony presumption (yes/no), contention (White/Black/others), drinking presumption (current/ever/never), smoking presumption (current/ever/never), carnal enactment (> 1 clip per week/1–3 times per month/never), household income (in quartiles), assemblage wide index, systolic humor pressure, and pulse complaint (all continuous) successful 2014/2016. P-values were adjusted utilizing the Benjamini-Hochberg methods
Associations of BWV, PRV, and BPV with mortality and epigenetic property acceleration
We observed non-heterogeneous associations of BWV, PRV, and BPV with mortality successful some HRS and CHARLS (P-heterogeneity > 0.05, Table 2). The pooled HRs (95% CIs) of mortality for each SD increment successful BWV, PRV, and BPV were 1.21 (95% CI: 1.15, 1.28), 1.06 (1.00, 1.13), and 1.12 (1.04, 1.19), respectively. The corresponding HRs (95% CIs) were 1.24 (1.15, 1.33), 1.07 (0.99, 1.16), 1.11 (1.03, 1.21) successful the HRS and 1.17 (1.07, 1.29), 1.05 (0.95, 1.17), 1.12 (1.01, 1.24) successful the CHARLS.
In the HRS-VBS, the associations of BWV, PRV, and BPV with EAA varied crossed epigenetic clocks (Additional record 1: Fig. S2 and Table S4). Larger PRV was related to importantly faster EAA successful GrimAge (β for per SD increment = 0.055 z-score, 95% CI: 0.005, 0.104). Larger BPV was associated with importantly faster EAA successful Zhang (0.079 z-score, 95% CI: 0.020, 0.138) and Horvath 1 (0.084 z-score, 95% CI: 0.020, 0.147). For different non-significant associations, the directions were mostly accordant with our hypotheses.
Sensitivity analyses
The results successful the sensitivity analyses were accordant with the superior findings (Additional record 1: Tables S5 and S6). When further adjusted for large wellness conditions, the relations of the composite people of variability to mortality and EAA persisted. When SD and VIM were utilized to measurement the variability successful physiological measures, the associations were comparable to the superior findings. When we replaced SBPV with DBPV, the relations were mostly unchanged. When we redefined the cutoffs for ample variability arsenic medians oregon alternatively assigned 0, 1, and 2 to the expanding tertiles of variability indicators, the relations of the composite people to mortality and EAA remained similar. When further adjusted for cell-type proportions successful the investigation of EAA, the relations were mostly the same.
Discussion
In 2 autarkic ample cohorts of middle-aged and older adults successful the USA and China, a higher composite people of semipermanent variability successful assemblage weight, pulse rate, and humor unit was related to a higher hazard of mortality autarkic of their baseline levels. Also, a higher people of variability was associated with faster EAA successful each 4 second-generation epigenetic clocks that are trained connected wellness outcomes. Aggregately, our findings suggest that instability successful large physiological measures mightiness beryllium an important predictor of mortality and an indicator of biologic aging successful middle-aged and older adults.
The existent survey is 1 of the fewer that has assessed the relations of variabilities successful physiological measures to mortality. In erstwhile studies, BWV [5], PRV [55], and BPV [16] person been associated with mortality separately. For example, successful the Framingham Heart Study, the highest grade of BWV was related to a higher hazard (27% successful men and 65% successful women) of mortality arsenic compared with those with the lowest BWV, which was confirmed by our investigation [5]. Although the idiosyncratic associations of the variabilities successful physiological measures with wellness outcomes have been wide explored [5, 33, 55, 56], small is known astir their combined relation with wellness outcomes. In a cohort survey of Korean adults, larger 13-year variability successful humor pressure, glucose, cholesterol, and BMI were related to higher mortality hazard successful the consequent 3 years, and the HR (95% CI) for mortality was 1.21 (1.18, 1.23) for each portion increment successful the people (range: 0–4) combining these indicators [33]. In our study, the combined and idiosyncratic associations of 8-year (in HRS) oregon 4-year (in CHARLS) variability successful physiological measures with mortality were consistently beardown successful 2 nationally typical cohorts successful the USA and China, and the associations were autarkic of the baseline levels of these physiological measures. Our findings suggested that a composite people constructed with semipermanent variability indicators successful non-invasive measurements whitethorn beryllium a caller predictor oregon hazard origin for mortality. However, whether the composite people is associated with semipermanent hazard of mortality and whether the associations are causal warrant further investigation.
To our knowledge, this is the archetypal survey relating semipermanent variability successful physiological measures to epigenetic aging. Previous studies person suggested that physiological dysfunction mightiness beryllium a effect of epigenomic modifications [40], but the relation betwixt them was acold from conclusive [57]. Our findings added invaluable grounds to the existent lit that semipermanent variability successful physiological measures could be predictors of EAA, which implied a imaginable nexus betwixt physiological homeostasis and DNA methylation [58]. Moreover, we recovered that the narration was much important successful the second-generation clocks than the first-generation clocks, perchance due to the fact that the second-generation clocks are much applicable to aging-related wellness outcomes than the first-generation clocks. Although the underlying biologic pathways stay mostly unknown, erstwhile studies person suggested a relation for methylation successful the crosstalk betwixt the adaptive immune strategy and physiological homeostasis [59]. Also, planetary DNA methylation mightiness besides bespeak abdominous organisation and homeostasis of definite biomarkers, though the absorption of the causal nexus has yet to beryllium confirmed [59]. Overall, by incorporating EAA, a reliable estimation of biologic aging [40], our findings item the quality of physiological variability to bespeak the gait of biologic aging. Our findings that the observed relation was autarkic of baseline levels of physiological presumption whitethorn suggest that longitudinal dynamic physiological statuses are important additions to their static values successful the appraisal of the gait of aging.
Several imaginable pathways could explicate the observed associations, including cardiac and vascular regularisation and inflammation, which were related to mortality and biologic aging, respectively. For example, BPV and PRV were associated with mediocre cardiac and vascular regularisation [60, 61], and BWV was linked to adipose insubstantial inflammation [62] and adipokine secretion alteration [63, 64]. Furthermore, the disturbance of homeostasis is often accompanied by inflammation [65], which whitethorn beryllium linked to DNA methylation and demethylation processes [66]. However, existent grounds is not capable for the assertion of their causal relation, arsenic vascular and metabolic dysfunction [67,68,69,70] could beryllium the communal reasons for the nonaccomplishment of homeostasis and faster aging. More experimental and observational studies are required to further uncover the analyzable relations and underlying mechanisms.
The strengths of the contiguous survey included the 2 nationally typical cohorts, the precocious rates of follow-up, the objectively measured exposures, and the comparatively ample illustration sizes. The high-quality epigenetic timepiece information besides enabled america to further measure the relation from a caller perspective. Nevertheless, our findings should beryllium interpreted with caution owed to immoderate limitations. First, our findings did not needfully suggest a causal nexus betwixt the variability indicators and mortality oregon EAA, arsenic residual confounding mightiness inactive exist. For example, we did not afloat relationship for intentional physiological changes, and physiological instability owed to underlying diseases could not beryllium afloat eliminated. Second, the follow-up duration for mortality was comparatively short, and aboriginal studies are needed to analyse the relation of variability successful physiological measures with mortality implicit a longer term. Third, we lone included participants who attended aggregate carnal examinations, which constricted the generalizability of our findings arsenic they mightiness beryllium healthier than the wide population. Moreover, portion the indicators were importantly related to EAA, the wide saltation explained was comparatively debased successful astir clocks (< 2% successful each clocks, information not shown). Although erstwhile studies besides reported a debased variance explained erstwhile assessing immoderate well-established hazard factors of aging, this mightiness bespeak the measurement errors successful DNA methylation. Lastly, the generalizability of our findings connected EAA should beryllium validated successful different populations, particularly fixed that DNA methylation whitethorn disagree crossed races and regions [71].
Conclusions
Our prospective survey suggests that a higher composite people of semipermanent variability successful physiological measures, including assemblage weight, pulse rate, and humor pressure, is related to an accrued hazard of mortality and faster epigenetic property acceleration autarkic of their baseline levels. Our findings underscored the imaginable relation of homeostasis attraction successful the aging process. Future probe is needed to corroborate the survey findings and to explore the underlying biologic mechanisms.
Availability of information and materials
The datasets that enactment the findings of this survey are disposable connected the HRS website (https://hrsonline.isr.umich.edu/) [23] and the CHARLS website (http://charls.pku.edu.cn/en/) [24].
Abbreviations
Body wide index
BPV:Blood unit variability
BWV:Body value variability
CHARLS:China Health and Retirement Longitudinal Study
CI:Confidence interval
CV:Coefficient of variation
DBPV:Diastolic humor unit variability
EAA:Epigenetic property acceleration
HR:Hazard ratio
HRS:Health and Retirement Study
PRV:Pulse complaint variability
SBPV:Systolic humor unit variability
SD:Standard deviation
VBS:Venous Blood Study
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Acknowledgements
The Health and Retirement Study is sponsored by the National Institute connected Aging (NIA U01AG009740) and the Social Security Administration. The survey manager is Dr. David R. Weir of the Survey Research Center astatine the University of Michigan’s Institute for Social Research. The China Health and Retirement Longitudinal Study was funded by the National Institute connected Aging (R01-AG037031 and R01AG067625), the Natural Science Foundation of China (72061137005, 81903392, 71603013, 72173008, and 71873010), and the China Medical Board (20-364). The authors would similar to convey the participants and workers of the HRS and CHARLS for their selfless contributions which made the existent survey possible.
Funding
This enactment was supported by the Zhejiang University Global Partnership Fund (granted to CY) and the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province (granted to YC, Grant No: 2020E10004). The backing organizations had nary relation successful the plan and behaviour of the study; collection, management, analysis, and mentation of the data; preparation, review, oregon support of the manuscript; and determination to taxable the manuscript for publication.
Ethics declarations
Ethics support and consent to participate
The HRS and HRS-VBS were approved by the Health Sciences and Behavioral Sciences organization reappraisal committee astatine the University of Michigan (HUM00061128). The CHARLS was approved by the Ethics Committee of Pecking University (00001052-11, 014).
Consent for publication
Not applicable.
Competing interests
The authors state that they person nary competing interests.
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Supplementary Information
Additional record 1: Fig. S1.
Participant inclusion and exclusion flowchart. Fig. S2. Scatter plots of BWV, PRV, and BPV with epigenetic property acceleration indicated by 4 second-generation epigenetic clocks. Table S1. Descriptive statistic of the 13 epigenetic clocks (N=1,047). Table S2. Associations of the composite people of variability successful physiological measures with mortality successful the HRS and CHARLS with antithetic adjustments. Table S3. Associations betwixt each one-point increment successful the composite people of variability and epigenetic property acceleration indicated by 13 first- and second-generation epigenetic clocks. Table S4. Associations of BWV, PRV and SBPV with epigenetic property acceleration indicated by 13 first- and second-generation epigenetic clocks. Table S5. Sensitivity analyses for the associations betwixt each one-point increment successful the composite people of variability with hazard of all-cause mortality. Table S6. Sensitivity analyses for the associations betwixt variability of physiological measures and epigenetic property acceleration.
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Chen, H., Zhou, T., Wu, S. et al. Long-term variability successful physiological measures successful narration to mortality and epigenetic aging: prospective studies successful the USA and China. BMC Med 21, 20 (2023). https://doi.org/10.1186/s12916-022-02674-w
Received: 23 August 2022
Accepted: 21 November 2022
Published: 16 January 2023
DOI: https://doi.org/10.1186/s12916-022-02674-w
Keywords
- Body value variability
- Pulse complaint variability
- Blood unit variability
- Mortality
- Epigenetic aging
English (US)