Objectives

The protocol study is designed to investigate the effect of the MBIs on inflammaging via a systematic review and meta-analysis. The objectives of this study include:

• Illustrate the relationship between the MBIs and the biomarkers, including PWV, FMD, TL, TA, TNF-α, IL-6, and CRP;
• Explore how the types of intervention, intervention duration, control-group types, subject health condition, and participants’ age account for the outcomes of the meta-analysis.

Review design

The protocol has been designed based on the guide book, preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) [11]. The review method was developed in accordance with the meta-analysis of observational studies in the epidemiology: a proposal for reporting [12], PRISMA-P checklist [13], and Cochrane Collaboration Handbook [14]. The study has been registered on PROSPERO (CRD42022321766).

Search strategy

Literature search will be conducted with Pubmed, Web of Science, Cochrane Central Register of Controlled Trials, and ProQuest Dissertation & Theses Global databases via the search terms in Table 1. Literatures will be collected until the systematic review and meta-analysis is published. The literature searching strategy combines mindfulness and nine parameters regarding to inflammaging and aging. The first theme is mindfulness, the second theme is IL-6 OR TNF-α OR CRP OR TL OR TA OR PWV OR FMD. The exploded versions of Medical Subject Heading of each theme will be included.

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Table 1. The search strategy.

https://doi.org/10.1371/journal.pone.0284228.t001

Inclusion criteria

Studies related to mindfulness and mentioned about the aging and inflammaging biomarkers will be included. The inclusion criteria are 1). academic articles and dissertations published in English, 2). participants aged > 18, 3). randomized controlled design, uncontrolled pretest-posttest design, or controlled without pretest-posttest design, 4). having mindfulness in the intervention, 5). presenting at least one of the nine biomarkers in the outcomes, 6). reporting appropriate data format of the outcomes for effect size calculation. The exclusion criteria were opposite to the inclusion criteria without additional limitation.

Data collection and management

Endnote X9 will be used in literature management. Data will be extracted and collected using the Microsoft Excel 16.3. Statistical analyses will be conducted using R 4.2.1.

Data extraction

For the eligibility (Fig 2), the studies retrieved from the databases will be grouped, and duplicated records will be removed. The titles and abstracts will be independently checked by two researchers following the inclusion criteria. Afterwards, the two researchers will read the full manuscripts to determine the included studies and clarify the reasons of the exclusions, independently. A third reviewer will intervene in case of disagreement, and a consensus will be sought. Two researchers will, again, independently extract the data regarding the author information, publication year of the studies, the gender, age, body mass index (BMI), health condition (e.g., healthy people, people with clinical diseases), and population (e.g., people with mindfulness practice experiences) of the participants, the type [e.g., mindfulness-based cognitive therapy (MBCT), mindfulness-based stress reduction (MBSR)] and length of intervention, study design [e.g., randomized controlled trial (RCT), uncontrolled pretest-posttest, or controlled without pretest-posttest design), and control condition (e.g., passive control, active control). A data extraction sheet will be made to include all the information mentioned. The information will be adapted in the case that relevant information is lack, and the authors of the included studies with missing key information will be contacted. The inconsistent coding will be discussed, and the final version will be confirmed among the three researchers.

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Fig 2. A flowchart of study selection.

https://doi.org/10.1371/journal.pone.0284228.g002

Outcomes and prioritization

The primary outcome of the meta-analysis is to record the impacts of the MBIs on PWV, FMD, TL, TA, TNF-α, IL-6, and CRP, respectively. The observational studies should report: 1) the sample sizes of the control and intervention groups (specific to pre- and post-tests for the RCTs); and 2) the mean and standard deviation values of the inflammaging or aging biomarkers for the control and intervention groups; or 3) other statistic records, such as F-test, t-test, or correlations; or 4) the effect sizes. These data will be used for synthesizing the effect size of each study and the pooled effect size further, or moderator analysis.

Risk of bias assessment of included studies

The risk of bias for the studies included in the systematic review and meta-analysis will be evaluated according to the the Cochrane bias risk assessment tool, which is recommended by the Cochrane Handbook. The studies will be assessed from six aspects: selection bias, implementation bias, measurement bias, follow-up bias, reporting bias, and other biases [14]. Two researchers will assess the risk of bias at the study level. A third researcher will join if discrepancy occurs.

Data synthesis

In the meta-analysis, a random effects model will be used. The standardized mean difference effect size of PWV, FMD, TL, TA, TNF-α, IL-6, and CRP from the eligible studies will be synthesized to investigate the effect of the MBIs on inflammaging [15]. To specific, the d_ppc [16] (standardized mean difference for a pre-post-control design) will be calculated for synthesizing the evidences from the RCTs, and Cohen’s d [17] will be calculated for synthesizing the evidences from the uncontrolled pretest-posttest and controlled without pretest-posttest designs, respectively. The heterogeneity will be tested by the Q statistic and quantified using I². The trial sequential analysis (TSA) will also be used to provide more information on the precision and uncertainty of meta-analysis. Moreover, publication bias will be analyzed with funnel plots. The Trim and Fill test will be applied to suggest the need of imputing missing cases if publication bias exist [18].

Depending on the data availability, the moderators, like the intervention type, intervention duration, control-group type, subject health condition, and participants’ age, will be analyzed accounting for the heterogeneity. Subgroup analysis will be applied to the following covariates: the type of intervention, control-group type, subject health condition, and participants’ age. And, meta-regression will be applied for the continuous covariates, e.g., the intervention duration.

A systematic narrative synthesis will be conducted for the consequential covariates with only limited data in the bulk of reports, which offers a comprehensive perspective in understanding the causality between MBIs and inflammaging, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines [19].

Ethics and dissemination

There will be no concerns about the privacy. All the data used in the systematic review and meta-analysis are extracted from registered trials, published studies, and unpublished dissertations. No ethics approval will be needed. Results of the meta-analysis and systemic review will be disseminated by publication in a peer-reviewed journal.