Evidence map›Paper›PMID 40033883›Full record

ArticleAging cell2025

Effects of the VIVIFRAIL Exercise Protocol on Circulatory and Intracellular Peripheral Mediators Bridging Mitochondrial Dynamics and Inflammation in Robust and Frail Older People.

Fiona Limanaqi, Evelyn Ferri, Pasquale Ogno, Franca Rosa Guerini, Gabriela Alexandra Mihali, Tiziano Lucchi, Mario Clerici, Chiara Fenoglio, Laura D'Andrea, Elena Marcello and 2 more

Abstract read
In one paragraph

Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Fiona LimanaqiDepartment of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.ORCID 0000-0003-0185-2099
Evelyn FerriIRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.ORCID 0000-0002-7423-3793
Pasquale OgnoDepartment of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Franca Rosa GueriniIRCCS Fondazione Don Carlo Gnocchi, ONLUS, Milan, Italy.ORCID 0000-0001-9461-5927
Gabriela Alexandra MihaliAsst Fatebenefratelli, Sacco, Milan, Italia, Italy.ORCID 0000-0003-3011-3607
Tiziano LucchiIRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.ORCID 0000-0002-2029-5120
Mario ClericiIRCCS Fondazione Don Carlo Gnocchi, ONLUS, Milan, Italy.ORCID 0000-0001-5920-6191
Chiara FenoglioIRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.ORCID 0000-0001-6332-4721
Laura D'AndreaDepartment of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", University of Milan, Milan, Italy.ORCID 0000-0002-2042-9782
Elena MarcelloDepartment of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", University of Milan, Milan, Italy.ORCID 0000-0003-0452-762X
Mara BiasinDepartment of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.ORCID 0000-0003-3671-4235
Beatrice ArosioDepartment of Clinical Sciences and Community Health, University of Milan, Milan, Italy.ORCID 0000-0002-0615-3580

Funding

Fondazione Cariplo 2017-0622
6 · The paper itself

Abstract

Physical exercise has been associated with healthier aging trajectories, potentially preventing or mitigating age-related declines. This occurs through a complex, yet poorly characterized network of multi-organ interactions involving mitochondrial, inflammatory, and cell death/survival pathways. Here, we comprehensively evaluated the 12-week VIVIFRAIL multicomponent exercise protocol in physically frail (n = 16, mean age 81.4 ± 5.6) and robust (n = 50, mean-age 73.6 ± 4.7) old individuals. Before (T0) and after (T1) the protocol, functional outcomes were assessed alongside a detailed exploratory analysis of mitochondrial, inflammatory, apoptotic, and neuro-muscular mediators concerning their plasmatic/serum concentrations, and/or mRNA expression from peripheral blood mononuclear cells (PBMCs). Besides significant functional improvements across both groups, our findings highlighted unique and overlapping modulations of key biological pathways. Both groups showed refined mitochondrial integrity/turnover (upregulated mt-ND1, downregulated TFAM, and ULK1), anti-inflammatory responses (upregulated IL10, and TGF-B, and downregulated IL6/IL10 mRNA ratio), as well as reduced cellular damage/apoptosis (reduced plasmatic ccf-nDNA, downregulated BAX, and upregulated BCL-2/BAX ratio). Plasmatic ccf-mtDNA was significantly reduced in robust subjects, while plasmatic IL6 and IL6/IL10 ratio were reduced in frail subjects uniquely. Spearman correlations between physical improvements and biological pathway variations also suggested different adaptation mechanisms influenced not only by chronological age but also by frailty status. In conclusion, this study confirms the benefits of physical activity in the older population and provides novel insights into specific biological mediators of the mitochondria-inflammation axis as key players in such effects. Moreover, our findings establish PBMCs as a valuable tool for monitoring the biological trajectories of aging and health-promoting lifestyle interventions.

Indexed as

ExerciseFrail ElderlyInflammationMitochondrial DynamicsAgedAged, 80 and overFemaleHumansLeukocytes, MononuclearMaleMitochondriaapoptosisccf‐mtDNAcytokinesexerciseinflammagingmitochondriamitophagyperipheral blood cells

Identifiers

PMID40033883
PMCPMC12151904

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.