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Metabolic Sensing and Adaptive Stress Responses in Aging and Chronic Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 951

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Guest Editor
1. Cellular and Humoral Immunology Laboratory (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania
2. The School of Life Sciences, Manchester Metropolitan University, Manchester M1 5QA, UK
Interests: C-reactive protein; stem cell; drug delivery; neurodegenerative disease; stroke; autoimmune disease
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Special Issue Information

Dear Colleagues,

I am pleased to invite you to contribute to a forthcoming Special Series entitled “Metabolic Sensing and Adaptive Stress Responses in Aging and Chronic Disease”. This series will bring together leading and emerging research that explores how cells, tissues, and organ systems sense metabolic, mechanical, and redox cues to maintain resilience across the lifespan.

A growing body of evidence suggests that pathways involved in energy sensing, mitochondrial quality control, autophagy, and redox homeostasis are central determinants of healthy aging and protection against chronic non-communicable diseases. Physical exercise, in particular, has emerged as a powerful physiological stimulus capable of engaging these pathways in a coordinated manner, offering mechanistic insights that extend beyond traditional pharmacological approaches.

The purpose of this Special Series is to provide a platform for interdisciplinary work spanning molecular and cellular biology, physiology, translational medicine, and clinical research. We especially welcome contributions that elucidate how metabolic stress signaling and exercise-induced adaptations modulate aging trajectories, reduce chronic inflammation, and confer protection against cardiovascular, metabolic, neurodegenerative, and inflammatory diseases.

By integrating fundamental mechanisms with translational perspectives, this Special Issue will advance our understanding of metabolic plasticity and identify actionable strategies for promoting healthspan and disease resilience. I warmly encourage you to submit original research articles, reviews, and perspectives that align with these themes, and I look forward to receiving your contributions.

With kind regards, 

Prof. Dr. Mark Slevin
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • metabolic sensing
  • aging and healthspan
  • exercise physiology
  • AMPK–mTOR signaling
  • autophagy and mitophagy
  • redox biology
  • mitochondrial quality control
  • cellular stress adaptation
  • chronic disease prevention
  • inflammaging

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Published Papers (1 paper)

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Review

24 pages, 1494 KB  
Review
Shear-Calibrated High-Intensity Interval Training to Promote Endothelial Autophagy and Delay Vascular Senescence: A Biomarker-Guided Approach
by Amelia Tero-Vescan, Ylenia Pastorello and Mark Slevin
Int. J. Mol. Sci. 2026, 27(6), 2653; https://doi.org/10.3390/ijms27062653 - 13 Mar 2026
Viewed by 708
Abstract
Vascular ageing is a complex process marked by progressive endothelial dysfunction, chronic low-grade inflammation (“inflammageing”), and reduced regenerative capacity, driven in part by an imbalance between protective endothelial autophagy and cellular senescence characterized by a proinflammatory senescence-associated secretory phenotype (SASP). Disruption of this [...] Read more.
Vascular ageing is a complex process marked by progressive endothelial dysfunction, chronic low-grade inflammation (“inflammageing”), and reduced regenerative capacity, driven in part by an imbalance between protective endothelial autophagy and cellular senescence characterized by a proinflammatory senescence-associated secretory phenotype (SASP). Disruption of this autophagy–senescence axis accelerates vascular inflammation, arterial stiffening, and atherogenesis. High-intensity interval training (HIIT), consisting of repeated bouts of near-maximal anaerobic effort with recovery periods, is widely used by both elite and recreational athletes and is increasingly recognized as an effective nonpharmacological strategy to enhance endothelial function, arterial elasticity, and mitochondrial biogenesis. However, excessively intense or poorly structured HIIT, particularly in the absence of adequate recovery or in individuals with underlying cardiometabolic or vascular vulnerability, may induce endothelial stress and promote maladaptive vascular remodelling, including calcification and plaque instability. These considerations underscore the need for refined individualized exercise prescription strategies that balance performance benefits with endothelial protection. Based on these observations, here, we introduce a novel conceptual framework, “shear dose–calibrated HIIT,” designed to understand and define an optimal shear dose capable of maximizing autophagic flux while minimizing SASP activation. Experimental and clinical evidence of HIIT-induced effects on flow-mediated dilation (FMD), pulse wave velocity (PWV), and redox biomarkers is presented, followed by the proposal of a biomarker panel for assessing autophagic flux and cellular senescence in peripheral samples (peripheral blood mononuclear cells (PBMCs), extracellular vehicles (EVs), and plasma). This integrative approach, which combines vascular mechanotransduction, redox biology, and autophagic signalling, provides a novel translational perspective on how individually calibrated HIIT can promote vascular longevity and reduce cardiometabolic risk associated with aging and metabolic syndrome. Full article
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