bims-mihora Biomed News
on Mitohormesis, repair and aging
Issue of 2026–06–21
fifteen papers selected by
Lisa Patel, Istesso
  1. Limiting neurodegeneration in ALS: A phosphatase paves the way.
  2. Integrated stress response couples mitochondrial fitness with lineage reprogramming to drive cancer evolution.
  3. Elevated mitochondrial protein import in acute myeloid leukemia increases reliance on mitochondrial protease LONP1.
  4. FGF21 reduces ER stress by enhancing the unfolded protein and integrated stress responses through increased sulfide signaling.
  5. The senescence-stiffening loop: Extracellular matrix remodeling, hypoperfusion, and mitochondrial dysfunction drive tissue aging.
  6. Senescence as a regulatory mechanism in skeletal muscle repair in young mice.
  7. Post-translational modifications of mitochondrion-related proteins: integrative orchestrators of cell fate networks in cardiovascular disease.
  8. From autophagy to mitophagy: Quality control mechanisms in skeletal muscle.
  9. Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.
  10. The effect of the integrated stress response reduction intervention on cellular aging in middle-aged nurses: a pilot study.
  11. Physiological amplitude: a systems-level framework for adaptive capacity in aging and metabolism.
  12. Multi-layered Regulatory Mechanisms and Translational Implications of Mitochondrial Redox Imbalance in Aging Stem Cells.
  13. Mitochondrial proteases maintain cellular protein homeostasis and tissue integrity.
  14. Homeodynamic Rejuvenation: an adaptive framework for resetting skin aging.
  15. From mice to humans-divergent strategies for intestinal homeostasis and regeneration.
  1. Neuron. 2026 Jun 17. pii: S0896-6273(26)00325-9. [Epub ahead of print]114(12): 2073-2075
    Limiting neurodegeneration in ALS: A phosphatase paves the way.
    Elena I Rugarli, Thomas Langer.
      Zheng et al. identify phosphatase PGAM5 as a novel promising target for the treatment of different amyotrophic lateral sclerosis subtypes. PGAM5 dephosphorylates and activates the stress-regulated mitochondrial peptidase OMA1, which elicits a maladaptive mitochondrial integrated stress response in motor neurons.
    DOI:  https://doi.org/10.1016/j.neuron.2026.04.030
  2. Nat Cell Biol. 2026 Jun 15.
    Integrated stress response couples mitochondrial fitness with lineage reprogramming to drive cancer evolution.
    Shiqi Diao, Jia Yi Zou, Shuo Wang, Jason E Chan, Roderik M Kortlever, Nicolas Poulain, Nour Ghaddar, Hyungdong Kim, Gerard I Evan, Constantinos Koumenis, Maria Hatzoglou, Peter Walter, Nahum Sonenberg, John Le Quesne, Tuomas Tammela, Antonis E Koromilas.
      Tumour progression towards dedifferentiated cell clusters plays a critical role in intratumour heterogeneity and therapy resistance. While tumour microenvironmental stress has been implicated, the underlying mechanisms remain poorly defined. Using mouse models of lung adenocarcinoma, we demonstrate that activation of the integrated stress response (ISR)-marked by phosphorylation of eIF2 (p-eIF2) and ATF4 induction-drives tumour heterogeneity. ISR activation facilitates the emergence of high-plasticity, undifferentiated and pre-epithelial-to-mesenchymal transition clusters characterized by elevated ATF4 and MYC activity. This process is MYC dependent and involves ISR-mediated repression of NKX2-1, a key determinant of alveolar identity, and induction of CHCHD10, a regulator of mitochondrial integrity and metabolic fitness. Disruption of the p-eIF2-ATF4 axis induces mitochondrial dysfunction, limits dedifferentiation and suppresses tumour growth. In human lung adenocarcinoma, ISR-driven dedifferentiation correlates with advanced disease and poor prognosis, identifying the ISR as a central driver of lineage reprogramming and metabolic fitness in tumour progression.
    DOI:  https://doi.org/10.1038/s41556-026-01991-z
  3. J Clin Invest. 2026 Jun 16. pii: e196687. [Epub ahead of print]
    Elevated mitochondrial protein import in acute myeloid leukemia increases reliance on mitochondrial protease LONP1.
    Matthew Tcheng, Veronique Voisin, Geethu Emily Thomas, Anastasija A Piric, Marcela Gronda, Rose Hurren, Dakai Ling, Yongran Yan, Lan Xin Zhang, Yue Feng, Ali Chegini, Nathan Duong, Ross S Mancini, Stefan Quinn W Currie, Zaynab Mamai, Brady Stock, Shahbaz Khan, Yulia Jitkova, Chaitra Sarathy, Edward Ayoub, Po Yee Mak, Andrea Arruda, Thomas Kislinger, Mark Reed, Bing Z Carter, Michael Andreeff, Steven M Kornblau, Mark D Minden, Siavash Vahidi, Aaron D Schimmer.
      Most mitochondrial proteins are nuclear encoded, translated in the cytosol, and imported into the mitochondria. Through gene expression analysis and functional assays, we demonstrated that mitochondrial protein import is increased in acute myeloid leukemia (AML) cells compared to normal hematopoietic cells. Increased mitochondrial protein import was positively correlated with increased mitochondrial unfolded protein response (UPRmt), a stress activated pathway of mitochondrial proteases and chaperones that maintains protein solubility and prevents the formation of toxic aggregates. The UPRmt protease LONP1 (Lon Peptidase 1) was upregulated in AML and positively correlated with increased mitochondrial protein import and UPRmt. Genetically or chemically inhibiting the LONP1 ATPase domain induced mitochondrial protein aggregation and selectively killed AML cells with high LONP1 expression while sparing AML cells with low LONP1 expression and normal hematopoietic cells in vitro and in vivo. Thus, we uncovered a critical role of the UPRmt protease LONP1 in buffering stress from mitochondrial protein import in AML.
    Keywords:  Cancer; Cell biology; Metabolism; Oncology
    DOI:  https://doi.org/10.1172/JCI196687
  4. Cell Metab. 2026 Jun 16. pii: S1550-4131(26)00221-4. [Epub ahead of print]
    FGF21 reduces ER stress by enhancing the unfolded protein and integrated stress responses through increased sulfide signaling.
    Gerald Grandl, Ann-Christine König, Fabian Metzger, Arkadiusz Liskiewicz, Tanja Hefele, Shelly Nason, Aaron Novikoff, Nada Al-Refaie, Md Abdur Rahman, Ahmed Khalil, Qian Zhang, Gustav Collden, Brian Finan, Jonathan Douros, Kirk Habegger, Alberto Cebrian-Serrano, Stefanie M Hauck, Matthias H Tschöp, Timo D Müller.
      Fibroblast growth factor 21 (FGF21) is an endocrine hormone with broad metabolic actions at supraphysiological concentrations but unclear physiological function, related to endoplasmic reticulum (ER) stress. ER stress activates the unfolded protein response (UPR), a cellular repair mechanism that maintains cellular homeostasis during protein folding stress. Using proximity labeling, we assessed the intracellular action of FGF21 at its receptor β-klotho (KLB) and discovered associations with protein folding in the ER, ER stress, and H2S production. We found that FGF21 increases enzymatic sulfide production and enhances, but does not initiate, the UPR. This FGF21 action is blunted by genetic or pharmacological inhibition of sulfide signaling and is phenocopied by an H2S donor in vivo. FGF21 modulating the UPR requires KLB, and even physiological levels of FGF21 modulate the UPR via increased hepatic H2S production. Collectively, we reveal a novel physiological role of FGF21 as an endocrine stress hormone that enhances the UPR via increased sulfide signaling.
    Keywords:  ER stress; FGF21; H(2)S; ISR, β-klotho, KLB; UPR; integrated stress response; sulfide signaling; unfolded protein response
    DOI:  https://doi.org/10.1016/j.cmet.2026.05.011
  5. Cell Metab. 2026 Jun 15. pii: S1550-4131(26)00193-2. [Epub ahead of print]
    The senescence-stiffening loop: Extracellular matrix remodeling, hypoperfusion, and mitochondrial dysfunction drive tissue aging.
    Luigi Ferrucci, Stefano Donega, Allison B Herman, Rafael de Cabo, Myriam Gorospe.
      Aging tissues experience a gradual decline in perfusion and metabolic resilience due to complex interactions among extracellular matrix (ECM) remodeling, vascular dysfunction, and mitochondrial impairment. Stiffening of the ECM that results from collagen crosslinking, elastin loss, and basement membrane thickening reduces vascular compliance and impairs local angiogenesis. The consequent reduction in capillaries and diminished endothelial reactivity leads to ongoing or intermittent hypoxia, which triggers changes in transcriptomic and proteomic programs that inhibit oxidative phosphorylation and facilitate the production of reactive oxygen species. Under these conditions, mitochondria produce less ATP than is needed for homeostatic repair. This energetic breakdown triggers cellular senescence and inflammation, further increasing ECM stiffening, and thus creating a self-sustaining feedback loop that accelerates tissue aging and functional decline. Such a continuum from ECM stiffening to mitochondrial dysfunction may be considered a new therapeutic target for strategies aimed at maintaining vascular integrity, mitochondrial health, and cellular homeostasis during aging.
    Keywords:  extracellular matrix; hypoperfusion; mitochondrial dysfunction; senescence
    DOI:  https://doi.org/10.1016/j.cmet.2026.05.008
  6. Am J Physiol Cell Physiol. 2026 Jun 18.
    Senescence as a regulatory mechanism in skeletal muscle repair in young mice.
    Amanda L Johnson, Ryan T Bevington, Gianni Parise.
      Senescence is broadly considered an age-related phenomenon; however, it also been implicated in normal tissue repair and wound healing. Skeletal muscle repair is a complex process that requires the coordination of several different cell populations but the role of senescence in skeletal muscle repair has yet to be fully elucidated. We hypothesize that senescence serves as a control mechanism throughout the regenerative process and the removal of senescent cells through senolytics will negatively impact the repair process in young mice. Briefly, young mice were exposed to either (a) vehicle (VEH), receiving only a cardiotoxin (CTx) injection in one hindlimb or (b) 7 days of senolytic treatment (SEN) pre-CTx and 3x/week for 4 weeks post-CTx. Dasatinib + Quercetin (D+Q) was used to selectively eliminate senescent cells. There were no significant differences between groups in functional measures such as hindlimb grip strength and cross-sectional area. eMHC+ fibers remained elevated at D28 in the SEN group. Macrophage infiltration was twice as high in the SEN group compared to VEH at D7. Satellite cell quantity and fibrotic area were significantly increased at D14 in the SEN group compared to VEH. We conclude that reducing senescent cells during muscle repair in young mice significantly altered the kinetics of muscle repair. Therefore, senescent cells may act as a regulatory mechanism in skeletal muscle to orchestrate the activity of the different cell populations involved in repair and regeneration such as immune cells, satellite cells, and fibrotic cells.
    Keywords:  Repair; Satellite cells; Senescence; Skeletal muscle
    DOI:  https://doi.org/10.1152/ajpcell.00154.2026
  7. Cell Commun Signal. 2026 Jun 13.
    Post-translational modifications of mitochondrion-related proteins: integrative orchestrators of cell fate networks in cardiovascular disease.
    Lei Liu, Saiteng Wu, Lei Zhang, Li Zhong, Rui Guo.
      Cardiovascular disease remains the leading cause of global mortality, with mitochondrial dysfunction playing a central pathogenic role. Post-translational modifications act as fundamental regulators of mitochondrial quality control. Yet, how mitochondrial post-translational modifications integrate stress signals to direct cell fate among diverse regulated cell death pathways in cardiovascular disease remains incompletely understood. This review proposes a conceptual framework in which mitochondrial post-translational modifications act as the master conductors of an integrated network linking mitochondrial homeostasis to cellular demise. We first outline the pivotal roles of mitochondrial quality control in cardiovascular disease and detail their precise mechanisms governed by mitochondrial post-translational modifications over each process. We then delineate how mitochondrial post-translational modifications critically regulate the initiation and execution of apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis, evaluating their distinct contributions to cardiovascular pathophysiology. Furthermore, we highlight the extensive crosstalk and convergence among these death modalities at the mitochondrial level, emphasizing the role of mitochondrial post-translational modification signatures in amplifying death signals or triggering modality switching. By synthesizing recent discoveries, this work connects dynamic protein-level modifications to cell fate outcomes, offering a theoretical basis for future therapeutic strategies aimed at rebalancing the network of mitochondrial post-translational modifications to combat heart failure and other cardiovascular diseases.
    Keywords:  Cardiovascular disease; Cell death; Dynamic equilibrium.; Mmitochondrial quality control; Post-translational modifications
    DOI:  https://doi.org/10.1186/s12964-026-03002-y
  8. Int Rev Cell Mol Biol. 2026 ;pii: S1937-6448(25)00162-5. [Epub ahead of print]404 1-61
    From autophagy to mitophagy: Quality control mechanisms in skeletal muscle.
    Eduardo Antuña, Nerea Menéndez-Coto, Paula Fernández-Guisasola, Ana Coto-Montes.
      Autophagy is a process which is responsible for the maintenance of cellular homeostasis. This is achieved through the orchestration of both highly selective and non-selective degradation pathways, the purpose of which is the elimination of damaged structures. Recent findings have revealed that, in addition to its intracellular function, this organelle exhibits a remarkable "social life" and forms relationships with other cellular organelles. This has led to the discovery that mitochondrial quality is maintained not only through mitophagy, but also through extracellular mechanisms between cells. This has significantly expanded our understanding of tissue integrity. In skeletal muscle, autophagy, or autophagy, is a finely tuned process that plays a crucial role in maintaining physiological performance and adaptation. Disruption of autophagy has been linked to accelerated degeneration, metabolic dysfunction, and frailty. Although therapeutic manipulation of autophagy and mitophagy shows promise in restoring muscle health, major translational barriers persist. A more profound and nuanced exploration of autophagy flux in human muscle is imperative, underpinned by novel advanced cell biology technologies and predicated on satellite cells as the primary agents in muscle regeneration. The full therapeutic potential of autophagy could be harnessed to redefine interventions against muscle ageing and associated diseases. However, this would still require critical scrutiny of the long-term effects and systemic consequences.
    Keywords:  Aging; Autophagy; Mitochondria; Quality control mechanisms; Skeletal muscle
    DOI:  https://doi.org/10.1016/bs.ircmb.2025.11.006
  9. FEBS J. 2026 Jun 16.
    Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.
    Tony Avril, Matthieu Le Gallo, Elodie Lafont.
      The endoplasmic reticulum (ER) is a cellular organelle frequently subjected to stress under both physiological and pathological circumstances, associated with the accumulation of mis/unfolded proteins in its lumen. To cope with this stress, cells have evolved an adaptive program called the unfolded protein response (UPR), whose primary function is to restore ER proteostasis. When the stress is prolonged, the UPR can also trigger cell death. The UPR controls multiple machineries involved in pre-emptive quality control (QC) of proteins prior to ER entry, ribosome-associated QC, protein folding within the ER, protein degradation through various processes, and export from the ER for secretion. Because the UPR and the machineries it controls play fundamental roles in determining cell fate, they are finely regulated, including through post-translational modifications (PTMs). In this review, we focus on the role of the ubiquitin and ubiquitin-like PTMs in the regulation and mediation of ER proteostasis. We specifically focus on three core processes: the UPR, ER-associated ribosome QC and ER-associated degradation. Lastly, we briefly discuss how Ub and Ubl also control the integrated stress response and the formation of inter-organelle membrane contact sites and thus act as general regulators of responses to cellular stresses beyond ER proteotoxicity.
    Keywords:  ER stress; ERAD; ER‐ribosomal quality control; endoplasmic reticulum; integrated stress response; ubiquitin; ubiquitin‐like; unfolded protein response
    DOI:  https://doi.org/10.1111/febs.70622
  10. BMC Nurs. 2026 Jun 13.
    The effect of the integrated stress response reduction intervention on cellular aging in middle-aged nurses: a pilot study.
    Hwasook Cho, Hyunwook Kang, MeiLing Song, Nahyun Kim.
       BACKGROUND: Nurses experience persistently high levels of occupational stress, which negatively impacts their health and the quality of patient care. Chronic psychological stress is closely linked to physiological dysregulation and cellular aging processes through stress-response pathways. However, limited evidence exists regarding whether stress management interventions targeting these mechanisms can influence cellular aging biomarkers in nurses. This study evaluated the effects of an Integrated Stress Response Reduction Intervention (iSRI) on cellular aging among middle-aged nurses.
    METHODS: A non-randomized controlled pilot study was conducted with 60 nurses aged 45-60 years recruited from two tertiary hospitals. Participants were allocated to either an intervention group (n = 31) or a control group (n = 29). The 12-week iSRI comprised biofeedback, cognitive-behavioral education, mindfulness, and exercise. Outcomes included perceived stress levels and biochemical markers (serum cortisol, IL-6, and SOD). Cellular aging was assessed via leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) using qPCR.
    RESULTS: Following the intervention, the iSRI group showed a significant decrease in perceived stress levels, with a significant group ⋅ time interaction (p =.012). Regarding biochemical markers, serum cortisol showed a significant group ⋅ time interaction (p =.001), although no significant between-group difference was observed post-intervention. SOD levels increased significantly in the intervention group compared to the control group (p =.031), showing a robust interaction effect (p =.001). Regarding cellular aging markers, a significant between-group difference in LTL was observed post-intervention (p =.002), and this difference remained significant after controlling for covariates (p =.047). However, the longitudinal effect for LTL was not statistically significant (p =.263). No significant changes were observed in IL-6 and mtDNAcn.
    CONCLUSIONS: The 12-week iSRI demonstrated an initial protective effect on preserving LTL, which was associated with reductions in perceived stress and subsequent improvements in cortisol and SOD. These findings suggest that mechanism-based stress management may help support telomere preservation, a hallmark of cellular aging. Given the exploratory nature of this pilot study, further larger-scale randomized controlled trials are warranted to confirm whether such interventions can induce sustained shifts in biological aging trajectories.
    TRAIL REGISTRATION: The study was registered in CRIS (KCT0011526; registration date: 23 January 2026; retrospectively registered).
    Keywords:  Biofeedback; Cellular senescence; Mitochondria; Non-randomized controlled trial; Nurses; Psychological stress; Telomere
    DOI:  https://doi.org/10.1186/s12912-026-04881-9
  11. Front Aging. 2026 ;7 1837722
    Physiological amplitude: a systems-level framework for adaptive capacity in aging and metabolism.
    Grazyna Sepczynska.
       Background: Aging is characterized by progressive loss of physiological complexity, inter-system coordination, and adaptive capacity. While mitochondrial dysfunction, metabolic inflexibility, impaired stress responses, and circadian dysregulation are well established, an integrative systems-level construct linking these processes remains lacking.
    Objective: To introduce physiological amplitude as a unifying framework describing the bounded dynamic range of coordinated variability across interacting physiological systems.
    Methods: We develop a conceptual, hypothesis-generating framework grounded in network physiology and systems biology, integrating mitochondrial function, metabolic flexibility, hormetic stress responses, and circadian regulation into a unified architecture of system-level adaptation.
    Results: Physiological amplitude is defined as the bounded dynamic range within which coordinated multiscale physiological dynamics are maintained. Aging is conceptualized as a progressive contraction of this accessible range across interconnected biological networks. This framework distinguishes physiological amplitude from variability and resilience by positioning it as a higher-order property emerging from constraint-defined interactions across physiological systems.
    Conclusion: Physiological amplitude provides an integrative framework for interpreting multiscale physiological dynamics and generates testable hypotheses for quantification using continuous monitoring and network-based analysis. As a candidate systems-level descriptor, it may support the development of integrative biomarkers of aging and metabolic decline, pending empirical validation.
    Keywords:  aging; circadian regulation; metabolic resilience; mitochondrial function; network physiology; physiological amplitude; physiological variability; redox biology
    DOI:  https://doi.org/10.3389/fragi.2026.1837722
  12. Free Radic Biol Med. 2026 Jun 18. pii: S0891-5849(26)00893-2. [Epub ahead of print]
    Multi-layered Regulatory Mechanisms and Translational Implications of Mitochondrial Redox Imbalance in Aging Stem Cells.
    Zi Ye, Shanshan Chen, Jiali Rui, Lumin Tang, Tianshi Wang, Qiuju Fan.
      Mitochondrial redox homeostasis is required for proper stem cell fate determination and tissue regeneration, and its dysregulation is a hallmark of aging-related stem cell dysfunction. This review systematically summarizes the multi-layered mechanisms by which aging-induced mitochondrial redox imbalance impairs stem cell identity, covering reactive oxygen species homeostasis, macromolecular metabolism, mitochondrial DNA integrity, mitochondrial dynamics, and the Sirtuin/forkhead box O (FoxO) signaling axis. We further highlight the context-specific metabolic features across different stem cell types and recent advances in targeted interventions to restore mitochondrial redox homeostasis, with a special focus on small molecule compounds with translational potential. This review further critically evaluates conflicting experimental evidence in current research, highlights major unresolved controversies and technical limitations in the field, providing a model that links mitochondrial redox status to epigenetic regulation for advancing both basic research and translational applications of mitochondrial redox-targeted interventions for stem cell aging.
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.06.038
  13. Cell Biosci. 2026 Jun 19.
    Mitochondrial proteases maintain cellular protein homeostasis and tissue integrity.
    Kexin Shi, Hao Liu, Hong Xu, Weina Shang, Liquan Wang, Chao Tong.
       BACKGROUND: Mitochondrial proteases are essential for mitochondrial protein import and constitute the core of the organelle's intrinsic protein quality control system. However, their physiological functions across tissues, as well as their influence on cytosolic proteostasis, remain incompletely understood.
    RESULTS: We generated loss- and gain-of-function alleles for 15 conserved mitochondrial proteases in Drosophila melanogaster to systematically dissect their in vivo functions. Disruption of specific proteases caused male sterility or organismal lethality, whereas tissue-specific knockouts in the eye, muscle, or fat body led to mitochondrial protein aggregates, structural defects, and age-dependent degeneration. Loss of UQCR-C1 or Afg3l2 robustly increased mitophagy, while overexpression of several proteases severely impaired muscle integrity. Loss of UQCR-C1, Mppa, or CG11771 promoted HTT72Q aggregation, and reducing UQCR-C1 or Afg3l2 markedly elevated cytosolic HTT72Q levels. Conversely, overexpressing Mppa-but with reduced efficacy in its disease-associated variants-suppressed HTT96Q aggregation and neuronal toxicity. Mppa forms a complex with UQCR-C1 to regulate mitochondrial pre-protein processing and import, indicating that enhancing mitochondrial protein import is sufficient to alleviate cytosolic proteotoxic stress caused by HTT polyglutamine (polyQ) proteins.
    CONCLUSIONS: This work establishes a comprehensive in vivo resource for mitochondrial protease functions and their roles in shaping cytosolic proteostasis.
    Keywords:   Drosophila ; Huntington disease (HTT) polyQ proteins; Mitochondria; Protease
    DOI:  https://doi.org/10.1186/s13578-026-01612-0
  14. Front Aging. 2026 ;7 1840035
    Homeodynamic Rejuvenation: an adaptive framework for resetting skin aging.
    Anthony Brown, Carla Simonetto, Carlos López-Otín.
      Skin aging reflects not only the accumulation of molecular damage, but also a progressive decline in the skin's ability to restore equilibrium under continuous environmental stress. Classical models distinguishing intrinsic and extrinsic aging do not fully capture this dynamic process. In this article, we introduce Homeodynamic Rejuvenation as the restoration of functional competence and biological vitality, achieved not through reversal of visible signs of aging, but by re-establishing the skin's ability to detect stress, coordinate adaptive responses, and recover efficiently following perturbation. Central to this framework is the concept of homeodynamic plasticity, which reflects the skin's intrinsic capacity to dynamically sustain function under environmental and metabolic stress. By integrating principles of homeodynamics with exposome biology, this approach targets the reactivation of the cellular systems that govern stress sensing, repair, and recovery. Five core biological processes, namely, intracellular quality control, regenerative competence, metabolic resilience, cellular integrity, and structural integrity, underpin homeodynamic plasticity. Disruption or failure of one or more of these processes results in progressive functional decline, culminating in skin aging, of which dermatoporosis, a chronic cutaneous insufficiency syndrome, represents a terminal manifestation. These interconnected processes provide a coordinated basis for both restoring and assessing skin function. We propose that Homeodynamic Rejuvenation is best evaluated through dynamic perturbation-recovery kinetics, which quantify the skin's ability to respond to and recover from stress. By linking these biological processes to measurable functional and clinical outcomes, Homeodynamic Rejuvenation offers a structured and translational framework for quantifying and restoring skin resilience.
    Keywords:  Homeodynamic Rejuvenation; adaptive capacity; exposome; extracellular matrix; homeodynamic plasticity; homeodynamics; photoaging; skin aging
    DOI:  https://doi.org/10.3389/fragi.2026.1840035
  15. FEBS Lett. 2026 Jun 19.
    From mice to humans-divergent strategies for intestinal homeostasis and regeneration.
    Keiko Ishikawa, Shinya Sugimoto, Toshiro Sato.
      The intestinal epithelium is maintained by stem cells that balance self-renewal and differentiation to sustain homeostasis and enable regeneration after injury. Recent advances-including organoid culture, genome editing, orthotopic xenotransplantation, and somatic mutation-based analysis-have created new opportunities to investigate intestinal stem cell (ISC) dynamics in humans. These studies have revealed striking species-specific differences: whereas mouse LGR5+ ISCs divide daily and are chemo-sensitive, human colonic LGR5+ stem cells are predominantly slow-cycling and chemo-resistant. Consistent with this reduced cycling, human ISCs accumulate somatic mutations more slowly than those of mice. Across mammals, ISC proliferation rates inversely correlate with lifespan, a relationship thought to minimize mutation accumulation and reduce cancer risk, in line with Peto's paradox. Regenerative responses in both mice and humans can involve fetal-like reprogramming driven by YAP and other signaling pathways, yet the extent of species differences in intestinal regenerative capacity remains unclear. This review synthesizes current insights into ISC kinetics, injury responses, and evolutionary adaptations, highlighting the need for human-focused studies to bridge translational gaps and guide regenerative medicine strategies.
    Keywords:  LGR5+ stem cell; colonic stem cell; fetal‐like reprogramming; intestinal stem cell; organoid; regeneration; slow‐cycling stem cell; somatic mutation rate
    DOI:  https://doi.org/10.1002/1873-3468.70387
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