bims-ripira 2026-03-29 papers

bims-ripira

Biomed News

on RRM2B MDMD in Adults

Issue of 2026–03–29
fourteen papers selected by
Martín Lopo

DCTPP1 orchestrates dCTP pool dynamics and mtDNA stability in quiescent cells.
Wernicke Encephalopathy Complicating a Distinctive POLG Phenotype With MNGIE-Like Features.
Evaluation of serum amyloid A as a biomarker for sepsis diagnosis compared with C-reactive protein, procalcitonin, and presepsin.
No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases.
Nicotinamide and Pyridoxine Supplementation Enhances Muscle Stem Cell Activity and Muscle Regeneration in Humans: A Randomized Placebo-Controlled Clinical Trial of High Force Eccentric Contraction Recovery in Healthy Young Men.
Astaxanthin protects heart mitochondria from damage caused by chronic alcohol intoxication.
Metabolic and mitochondrial alterations in children with autism spectrum disorder: The role of FGF-21 and GDF-15.
A nutritional blend of taurine, vitamins B6, B9, and B12 improves motivated behaviors in healthy adults-a double-blinded randomized clinical trial.
Renin-angiotensin system blockade attenuates brain mitochondrial dysfunction, oxidative stress, and neuroinflammation associated with hypertension, metabolic disorders, and aging.
Mediterranean diet adherence is associated with mitochondrial microproteins Humanin and SHMOOSE; potential role of the Humanin-Nox2 interaction in cardioprotection.
The Role of Omega-3 Polyunsaturated Fatty Acids on Sarcopenia and Aging Muscle.
Quadriceps mitochondrial DNA quantity, quality, and gene expression after 2 years of calorie restriction: exploratory results from the CALERIE trial.
Mitochondrial Impairment in Unloaded Postural Muscle: Mechanisms Driving Loss of Muscle Function and Mass.
People over 60 feel younger in the morning: A good time of day to enhance wellbeing?

Cell Death Dis. 2026 Mar 26.

DCTPP1 orchestrates dCTP pool dynamics and mtDNA stability in quiescent cells.

Belén Fernández, Guiomar Pérez-Moreno, Blanca Martínez-Arribas, Antonio E Vidal, Luis Miguel Ruiz-Pérez, Dolores González-Pacanowska.

Defects in nucleotide metabolism and imbalances in deoxynucleotide triphosphate (dNTP) pools are associated with several human diseases, including cancer and mitochondrial disorders. In non-replicative cells, while DNA synthesis is reduced, a continuous supply of nucleotides is essential to sustain mitochondrial DNA (mtDNA) replication and repair. Human all-α dCTP pyrophosphatase 1 (DCTPP1), a nucleotido hydrolase with high specificity for dCTP, plays a critical role in maintaining nucleotide homeostasis, however its participation in mtDNA stability remains unexplored. In this study we performed a detailed analysis of pyrimidine metabolism enzymes in non-dividing cells. We found that during quiescence, DCTPP1 is predominantly localized to mitochondria. Depletion of the enzyme leads to upregulation of the de novo thymidylate synthesis pathway and expansion of both the dCTP and dGTP pools, highlighting its pivotal role in regulating the dNTP balance. To explore the potential therapeutic relevance of these observations, we used an in vitro model of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a rare mitochondrial disorder caused by thymidine phosphorylase (TP) deficiency and characterized by dCTP depletion and mtDNA loss. Long-term thymidine overloading in quiescent cells (a model mimicking TP deficiency) led to reduced dCTP levels and the depletion of mtDNA, effects that were reversed upon DCTPP1 knockdown. Hence, reduced DCTPP1 levels restored dCTP availability and increased mtDNA copy number. These findings suggest that DCTPP1 plays a critical role in regulating mitochondrial dNTP pools and that down-regulation of the enzyme may serve as a compensatory mechanism in disorders marked by secondary dCTP depletion. DCTPP1 may therefore represent a promising therapeutic target for mitochondrial DNA depletion syndromes such as MNGIE.

DOI: https://doi.org/10.1038/s41419-026-08632-1
Eur J Neurol. 2026 Mar;33(3): e70554

Wernicke Encephalopathy Complicating a Distinctive POLG Phenotype With MNGIE-Like Features.

Giuliana Capece, Luca Caumo, Sara Volta, Pietro Riguzzi, Elena Sogus, Angela Petrosino, Sara Vianello, Daniele Sabbatini, Leonardo Salviati, Renzo Manara, Carlo Viscomi, Gianni Sorarù, Luca Bello, Elena Pegoraro.

   BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an extremely rare autosomal recessive disease caused by variants in the thymidine phosphorylase gene (TYMP), primarily characterized by severe gastrointestinal and neurological symptoms. The complete phenotype of MNGIE has not been linked to any gene other than TYMP.
METHODS: We describe two identical twins who exhibited delayed psychomotor development, infantile bilateral cataract, congenital demyelinating polyneuropathy, and severe progressive gastrointestinal dysmotility with recurrent pseudo-obstruction episodes, along with diffuse supratentorial leukoencephalopathy that mainly overlaps with classic TYMP-related MNGIE. During the course of the disease, one patient developed Wernicke encephalopathy, triggered by chronic malnutrition related to recurrent gastrointestinal pseudo-obstruction. This patient later suffered from a catastrophic stroke-like episode, resulting in massive cerebral edema and brain death at the age of 38.
RESULTS: Next-generation sequencing (NGS) using a custom-targeted mitochondrial gene panel identified two compound heterozygous variants in the POLG gene: the paternal variants p.Thr251Ile and p.Pro587Leu, occurring in cis, and the novel maternal variant p.Arg853Gly. Quantification of mtDNA by real-time PCR on skeletal muscle DNA detected significant depletion, but no multiple deletions were detected with mtDNA analysis by long-range PCR and Nanopore sequencing.
CONCLUSIONS: These cases showed a very distinctive POLG phenotype, with some MNGIE-like features, expanding the clinical and genetic spectrum of the POLG-related diseases. Additionally, they highlighted the importance of monitoring for thiamine deficiency in mitochondrial patients with severe gastrointestinal dysmotility who experience sudden clinical deterioration.

Keywords:  central nervous system diseases; malabsorption syndromes; mitochondrial diseases; mitochondrial encephalomyopathies

DOI:  https://doi.org/10.1111/ene.70554
Lab Med. 2026 Feb 09. pii: lmaf054. [Epub ahead of print]57(2):

Evaluation of serum amyloid A as a biomarker for sepsis diagnosis compared with C-reactive protein, procalcitonin, and presepsin.

Myeong Hee Kim, So Young Kang, Woo-In Lee, Min Young Lee.

   INTRODUCTION: Several biomarkers have been developed for rapid and accurate diagnosis of sepsis. This study aimed to evaluate the potential of serum amyloid A (SAA) as a biomarker for sepsis diagnosis compared with C-reactive protein (CRP), procalcitonin (PCT), and presepsin.
METHODS: Biomarker levels were measured in 193 patients. Blood and microbial cultures were obtained from 69 and 94 patients, respectively. Based on the culture results and clinical symptoms, patients were classified into groups with sepsis, local infection, inflammatory disease, or other conditions to evaluate the differences in the values of the 4 biomarkers.
RESULTS: Serum amyloid A, CRP, and PCT levels were high in both the sepsis and localized infection groups, whereas SAA also showed increased levels in the inflammatory disease group. The area under the curve for diagnostic ability of SAA, CRP, PCT, and presepsin were 82.6%, 82.0%, 90.3%, and 85.7%, respectively. In the statistical association analysis, SAA showed a positive correlation with the 3 other biomarkers, with the best correlation observed with CRP.
DISCUSSION: The application of SAA in the early diagnosis of sepsis holds substantial clinical promise, particularly when employed alongside established biomarkers such as PCT, CRP, and presepsin. This combinatory approach may enhance diagnostic accuracy.

Keywords:  CRP; presepsin; procalcitonin; sepsis; serum amyloid A

DOI:  https://doi.org/10.1093/labmed/lmaf054
Eur J Immunol. 2026 Apr;56(4): e70176

No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases.

Manon Marchais, Alessandra Pennisi, Alexandre Pierga, Alice Lepelley, Nicolas Cagnard, Christine Bole, Patrick Nitschke, Mohamed Hamici, Frédéric Rieux-Laucat, Manuel Schiff, Arnold Munnich, Agnès Rötig.

Mitochondria have long been known to be involved in the regulation of innate immune response. We questioned whether cultured skin fibroblasts of patients suffering from mitochondrial diseases are valuable biological resources for the study of interferon signaling. Expression of interferon-stimulated genes was measured in control cells supplemented with interferon and in cultured fibroblasts of patients carrying pathogenic variants in mitochondrial disease-causing genes. Control fibroblasts showed a strong expression of interferon-stimulated genes in response to interferon, but only 43% of patients' fibroblasts displayed increased interferon stimulated genes scores. Cytosolic mitochondrial DNA and RNA were quantified by immunofluorescence and confocal microscopy. No correlation between elevated interferon response and cytosolic mitochondrial DNA or RNA release could be established. We found that cultured skin fibroblasts represent a valuable biological resource for the investigation of interferon signaling, but that abnormal interferon signaling is not always observed in patients with mitochondrial diseases. At variance to gene silencing in control fibroblasts, the lack of correlation between elevated interferon response and cytosolic mitochondrial DNA or RNA leakage in patients' fibroblasts questions the relevance of cellular models as illustrators of pathological situations in humans.

DOI: https://doi.org/10.1002/eji.70176
Adv Sci (Weinh). 2026 Mar 24. e18471

Nicotinamide and Pyridoxine Supplementation Enhances Muscle Stem Cell Activity and Muscle Regeneration in Humans: A Randomized Placebo-Controlled Clinical Trial of High Force Eccentric Contraction Recovery in Healthy Young Men.

Grith Højfeldt, Joris Michaud, Ann Damgaard, Karoline Karlog, Eugenia Migliavacca, Sonia Karaz, Elham Pazirandeh-Micol, Odd E Johansen, Leonidas G Karagounis, Bjørk W Helge, William Hagemann, Michael Kjaer, Jerome N Feige, Pascal Stuelsatz, Abigail L Mackey.

  Muscle Stem Cells (MuSCs) drive muscle regeneration and slow pathological progression of muscle diseases. In preclinical models, nicotinamide (NAM) and pyridoxine (PN) synergistically increased MuSC proliferation and differentiation, and accelerated muscle regeneration. Herein we tested if NAM/PN could enhance MuSC activity and muscle regeneration in a randomized, placebo-controlled clinical trial. Men aged 18-49 years were supplemented daily with 714 mg NAM and 19 mg PN, or placebo, for 9 days following one session of damaging unilateral eccentric muscle contractions. The primary endpoint was MuSC activity via immunohistofluorescence on biopsy sections from the vastus lateralis muscle. Histological markers of muscle regeneration constituted secondary outcomes, and muscle damage was validated with clinical markers. 39 out of 43 enrolled participants completed the study. Supplementation of NAM/PN was well tolerated and increased blood concentrations of NAM and PN vitamers. 8 days after the contraction protocol, the number of Pax7, MyoD, and myogenin positive cells per damaged fiber was significantly higher in NAM/PN vs placebo groups (+29%-67%). NAM/PN also increased the proportion of regenerating fibers (+37%). Daily oral NAM/PN supplementation after high intensity muscle contractions enhances MuSC activity and accelerates muscle regeneration and repair, providing new opportunities for therapeutic applications in muscle recovery and muscle wasting disorders.

Keywords:  human muscle regeneration; muscle stem cell; muscle therapeutics; nicotinamide; pyridoxine; randomized placebo‐controlled clinical trial

DOI:  https://doi.org/10.1002/advs.202518471
Biomed Khim. 2026 Feb;72(1): 28-41

Astaxanthin protects heart mitochondria from damage caused by chronic alcohol intoxication.

O V Krestinina, I V Odinokova, A I Zvyagina, R R Sotnikov, L D Sotnikova, Yu L Baburina.

  The natural antioxidant astaxanthin (AST) demonstrates the cardioprotective effect on cardiac mitochondria in rats subjected to chronic alcohol intoxication. Particularly, AST restored cardiac mitochondrial respiratory activity and Ca2+ capacity of rats exposed to chronic alcohol intoxication; it also had a positive impact on the balance of functionally important processes of mitochondrial fission/fusion, as well as mitophagy. In addition, AST prevented alcohol-induced morphological damage to cardiac tissue. Overall, the results demonstrate that AST promotes normalization of cardiac mitochondrial function, protecting these organelles from degenerative changes caused by alcohol intoxication and improving cardiac energy metabolism. Thus, AST helps to compensate the cardiac mitochondrial damage caused by chronic alcohol intake by restoring their functional activity and stress resistance.

Keywords:  astaxanthin; cardiac mitochondria; chronic alcohol intoxication; mitochondrial dysfunction; mitochondrial fission/fusion; mitophagy

DOI:  https://doi.org/10.18097/PBMCR1617
Clin Chim Acta. 2026 Mar 22. pii: S0009-8981(26)00161-0. [Epub ahead of print]588 120979

Metabolic and mitochondrial alterations in children with autism spectrum disorder: The role of FGF-21 and GDF-15.

Ayla Yildiz, Hanim Seyma Topuz, Hasan Onal.

   INTRODUCTION: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition marked by social communication deficits and repetitive behaviors. Evidence suggests that metabolic and mitochondrial stress contribute to ASD. Fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) are circulating markers of mitochondrial dysfunction and cellular stress, but their role in pediatric ASD remains underexplored.
METHODS: Case-control study involved 118 children: 88 with ASD (DSM-5 criteria) and 30 healthy controls matched by age and sex. ASD patients were divided by Autism Behavior Checklist (ABC) scores into Group I (ABC >60, n = 48) and Group II (ABC ≤60, n = 40). FGF-21 and GDF-15 were measured by ELISA. Biochemical parameters, hemogram, plasma amino acids (LC-MS/MS), and urinary organic acids (GC-MS) were analyzed. Statistical analyses included Kruskal-Wallis, Spearman correlation and ROC.
RESULTS: FGF-21 was significantly elevated in ASD compared to controls (p < 0.0001), while GDF-15 showed no difference (p = 0.797). FGF-21 did not differ between Group I and Group II (p > 0.05). ASD showed increased lactate, lactate/pyruvate ratio, urea, AST, LDH, LDL, lymphocyte and platelet counts, and decreased pyruvate, serum and urinary creatinine (p < 0.05). Essential and branched-chain amino acids decreased, whereas glycine and histidine increased (p < 0.05). FGF-21 correlated weakly but significantly with mitochondrial dysfunction and amino acid metabolism markers. ROC showed good diagnostic accuracy for FGF-21 in ASD (AUC = 0.817), with 98.9% sensitivity and 73.3% specificity at 27.9 pg/mL cut-off. Urinary organic acids, methylmalonic acid, tiglylglycine, and 2-ketoisocaproic acid, were significantly elevated (p < 0.05).
CONCLUSION: Elevated serum FGF-21 in children with ASD is linked to metabolic alterations, whereas GDF-15 remains unchanged. These results suggest FGF-21's association with metabolic dysregulation in ASD.

Keywords:  Amino acid; Autism spectrum disorder; Biomarkers; Fibroblast growth factor 21; Growth differentiation factor 15; Mitochondrial stress

DOI:  https://doi.org/10.1016/j.cca.2026.120979
Front Nutr. 2026 ;13 1711478

A nutritional blend of taurine, vitamins B6, B9, and B12 improves motivated behaviors in healthy adults-a double-blinded randomized clinical trial.

Veeda Michelle Anlacan, Roland Dominic G Jamora, Laura-Florina Krattinger, Evelina De Longis, Mickaël Hartweg, Myriam Steinmann, Laura Trovò.

   Introduction: Motivation is a key driver in achieving goals and performing daily tasks, involving cost-benefit valuations of the amount of effort required for a particular reward and can be influenced by socio-environmental factors and neurological conditions that may impact the brain reward circuitry. Notably, research has shown that higher glutathione levels (GSH) in the nucleus accumbens are linked with better and more consistent performance in effortful tasks in both preclinical models and humans.
Methods: Building on these findings, we identified candidate nutrients found in foods that could enhance brain GSH production as a possible approach to sustain motivated behaviors. In primary astrocytes in vitro, we discovered that taurine was able to efficiently increase GSH production and protect mitochondria from oxidative stress damage, but only when levels of vitamin B9 were adequate. The above led us to test a blend of taurine, vitamin B6, B9, and B12 in humans, in a randomized, double-blind, 2-arm, cross-over study with 44 participants aged 25-40 years old. We assessed the impact of four-week supplementation of taurine, vitamins B6, B9, and B12 on effortful motivated behaviors. Motivational performance was measured by the Monetary Incentive Delay Task coupled to a physical effort after 14 days and 28 days of supplementation.
Results: Results showed significant improvements after 14 days supplementation in the first period, as well as after 28 days in the second administration period, compared to placebo. Notably, when receiving the active blend, participants showed a consistent motivational performance throughout the task. The blend was also found to reduce the number of lapses during the Psychomotor Vigilance Task after 14 days, but not after 28 days of intake.
Discussion: Overall, these findings demonstrate how targeted nutritional supplementation can sustain brain health and modulate behaviors, such as motivated and goal-oriented performance.
Clinical trial registration: https://clinicaltrials.gov/study/NCT05733364, NCT05733364.

Keywords:  B vitamins; antioxidant; mental performance; motivation; taurine

DOI:  https://doi.org/10.3389/fnut.2026.1711478
World J Exp Med. 2026 Mar 20. 16(1): 113259

Renin-angiotensin system blockade attenuates brain mitochondrial dysfunction, oxidative stress, and neuroinflammation associated with hypertension, metabolic disorders, and aging.

Sebastián García Menéndez, Felipe Inserra, Elena Mv de Cavanagh, Leon Ferder, Walter Manucha.

  Although aging is an inherent part of life, it represents a process of progressive dysfunction rather than a fixed biological outcome. Consequently, highly prevalent conditions such as cardiorenal-metabolic syndrome-which encompasses obesity, hypertension (HTN), and metabolic disorders-can accelerate age-related changes. The renin-angiotensin system (RAS) plays a critical role in pathophysiology and affects multiple organs, including the brain. The central nervous system contains both RAS branches: The ACE/Ang II/AT1 and AT2 receptor axis, as well as the ACE2/Ang-(1-7)/Mas receptor axis. Neuroinflammation is a chronic process characterized by glial cell activation triggered by increased production of reactive oxygen and nitrogen species, resulting in oxidative stress. Mitochondria are the primary cellular sites where these processes occur. Under conditions such as metabolic disorders, obesity, HTN, and aging, these reactions are markedly accelerated. Associated mechanisms include insulin resistance, elevated levels of advanced glycation end-products, and disruption of the blood-brain barrier. The consequences of these alterations may include brain dysfunction, cognitive decline, Parkinson's disease, and neurodegenerative conditions such as Alzheimer's disease. This review focuses on the primary effects of therapeutic interventions on mitochondrial function, with particular attention to the modulation of oxidative stress, chronic neuroinflammation, and glial dysregulation. We highlight the strategic use of angiotensin receptor blockers and ACE2 activators as promising tools that may redefine the prevention and treatment of vascular dementia and other neurodegenerative diseases of inflammatory origin.

Keywords:  Aging; Central nervous system inflammation; Hypertension; Metabolic disorders; Mitochondria; Neurodegeneration; Oxidative stress; Renin-angiotensin system blockade

DOI:  https://doi.org/10.5493/wjem.v16.i1.113259
Front Nutr. 2025 ;12 1727012

Mediterranean diet adherence is associated with mitochondrial microproteins Humanin and SHMOOSE; potential role of the Humanin-Nox2 interaction in cardioprotection.

Roberto Vicinanza, Vittoria Cammisotto, Junxiang Wan, Kelvin Yen, Francesco Violi, Pasquale Pignatelli, Pinchas Cohen.

   Background: The health benefits of the Mediterranean Diet (Med-Diet) have been demonstrated in observational studies and randomized controlled trials. Emerging evidence suggests that the biological effects of the Med-Diet may be mediated by the modulation of mitochondrial function. Human mitochondrial DNA (mtDNA) encodes microproteins, which have been shown to regulate aging, cardiometabolic functions, and neuroprotection.
Objectives: To investigate Humanin and SHMOOSE (Small Human Mitochondrial ORF Over SErine tRNA), as potential mitochondrial biomarkers of Med-Diet adherence and their associations with markers of oxidative stress.
Methods: Cross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome. Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire. Oxidative stress was evaluated by measuring soluble Nox2-derived peptide (sNox2-dp) and plasma 8-iso-prostaglandin F2α (8-iso-PGF2α) using enzyme-linked immunosorbent assays (ELISA). Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.
Results: High Med-Diet adherence was observed in 20 patients (40.8%), while 29 patients (59.2%) had low-medium adherence. Patients with high adherence exhibited higher plasma levels of SHMOOSE (p = 0.046) and Humanin (p = 0.045). The analysis of the dietary components of the Med-Diet revealed higher levels of SHMOOSE with olive oil consumption (p = 0.020) and low intake of refined bread (p = 0.029), while Humanin positively correlated with olive oil (p = 0.0069), fish (p = 0.038), and legumes (p = 0.0282). Additionally, Humanin was inversely associated with sNox2-dp (p = 0.019), which remained significant after adjusting for sex and BMI (B = -0.010; β = -0.302; p = 0.040), and 8-iso-PGF2α (p = 0.049).
Conclusion: This study indicates (i) a positive association between adherence to the Med-Diet and circulating levels of mitochondrial microproteins SHMOOSE and Humanin supporting their role as potential mediators of Med-Diet benefits; (ii) a putative crosstalk between Humanin signaling and Nox2 activity, suggesting a novel cardioprotective mechanism of the Med-Diet. Collectively, these findings support mitochondrial microproteins as promising biomarkers for tailoring nutritional strategies for healthy aging. Further studies are warranted to elucidate the underlying mechanisms and determine the causal nature of these associations.

Keywords:  Humanin; Mediterranean diet; Nox2; SHMOOSE; cardioprotection; healthspan; mitochondrial microproteins; oxidative stress

DOI:  https://doi.org/10.3389/fnut.2025.1727012
Int J Environ Res Public Health. 2026 Mar 11. pii: 355. [Epub ahead of print]23(3):

The Role of Omega-3 Polyunsaturated Fatty Acids on Sarcopenia and Aging Muscle.

Behzad Varamini, Jonah O Yang, Benjamin J Merry, Daniel J Dau.

  Sarcopenia, characterized by the progressive loss of skeletal muscle mass, strength, and function, represents a major public health challenge in aging populations. This condition affects approximately 10-16% of community-dwelling older adults and is associated with increased risks of falls, frailty, functional decline, and mortality. The pathogenesis of sarcopenia involves chronic low-grade inflammation (inflammaging), oxidative stress, mitochondrial dysfunction, and anabolic resistance. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have emerged as promising nutritional interventions due to their anti-inflammatory properties and potential anabolic effects on skeletal muscle. This comprehensive review evaluates the current evidence on omega-3 PUFA supplementation for the attenuation and management of sarcopenia. Mechanistically, omega-3 PUFAs appear to enhance muscle protein synthesis through activation of the mTOR-p70S6K signaling pathway, reduce inflammation via specialized pro-resolving mediators (SPMs), improve mitochondrial bioenergetics, and attenuate muscle disuse atrophy. Clinical trials demonstrate that omega-3 supplementation, particularly at doses exceeding 2 g/day of combined EPA and DHA, can increase thigh muscle volume, handgrip strength, and one-repetition maximum strength in older adults. When combined with resistance exercise training, the benefits appear more pronounced, especially in women. However, heterogeneity in study designs, intervention durations, dosages, and outcome measures has produced some conflicting results. Large-scale trials, such as the MAPT study, have shown null findings for long-term supplementation alone, suggesting that omega-3s may be most effective as part of multimodal interventions. The evidence also supports benefits in clinical populations at risk for muscle wasting, including cancer patients experiencing cachexia and individuals with neuromuscular disorders. Future research should focus on identifying optimal dosing strategies, understanding sex-specific responses, and elucidating the mechanisms underlying the synergistic effects of omega-3s with exercise. Overall, omega-3 PUFA supplementation represents a safe, accessible, and potentially effective nutritional strategy for attenuating muscle decline in aging and clinical populations, though its benefits appear most pronounced when combined with resistance exercise as part of a multimodal approach.

Keywords:  DHA; EPA; aging; inflammation; mTOR signaling; muscle protein synthesis; omega-3 polyunsaturated fatty acids; resistance training; sarcopenia

DOI:  https://doi.org/10.3390/ijerph23030355
Geroscience. 2026 Mar 26.

Quadriceps mitochondrial DNA quantity, quality, and gene expression after 2 years of calorie restriction: exploratory results from the CALERIE trial.

Jayanta K Das, Yu Zhang, Leanne M Redman, Corby K Martin, Sai Krupa Das, Susan B Racette, Allen Herbst, Nianjun Liu, David B Allison, Debbie McKenzie, Judd M Aiken, Steve Horvath, Julián Candia, Nirad Banskota, Luigi Ferrucci, William E Kraus, Kim M Huffman, Jonathan Wanagat.

  The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)™ trial was a randomized, 2-year controlled trial of caloric restriction (CR) versus an ad libitum (AL) control condition in nonobese humans. We performed exploratory analyses of muscle mitochondrial DNA (mtDNA) integrity, one element of mitochondrial quality. Our aims were to assess the feasibility of this approach, explore associations to inform future hypotheses, estimate effect sizes and statistical power for subsequent studies, and contribute additional data to the CALERIE database. We used droplet digital PCR to quantitate the copy numbers of nuclear DNA, mtDNA, and mtDNA deletion mutations in remnant total DNA samples extracted from quadriceps biopsies at baseline (n = 93), 12 months (n = 44), and 24 months (n = 31). MtDNA copy number and mutation frequency were correlated with existing gene expression data from the same muscle biopsies. MtDNA copy number was lower in females (p = 0.0005) and declined over time (p = 0.0001), with no statistically significant differences observed for CR versus AL (p = 0.2898) or age across both groups (p = 0.4644). Baseline copy number correlated positively with baseline physiological measures including fat-free mass (r = 0.43, p = 2e-05), self-reported energy intake (r = 0.34, p = 0.00077), resting metabolic rate (r = 0.42, p = 0.00261), total energy expenditure (r = 0.31, p = 0.00261), and V̇O₂max (r = 0.41, p = 1e-04), and with gene expression related to mitochondrial function, while showing negative correlations with nuclear genome maintenance, RNA splicing, and ribosomes. MtDNA mutation frequency increased with age (p = 0.0041) and showed a weak negative correlation with V̇O2max (r = -0.23, p = 3e-05). MtDNA mutation frequency was not statistically different with CR. Mutation frequency was positively correlated with gene expression changes in inflammation and negatively correlated with protein translation. We observed that, as expected, mtDNA copy number declined over time, was lower in females, and correlated with metabolic measures and mitochondrial gene expression, suggesting its potential utility as a marker of metabolic health. These findings contribute to understanding mitochondrial adaptations to CR and highlight potential benefits of CR interventions.

Keywords:  Calorie restriction; DNA; Gene expression; Human; Mitochondria; Mutation

DOI:  https://doi.org/10.1007/s11357-026-02167-1
Antioxidants (Basel). 2026 Feb 24. pii: 277. [Epub ahead of print]15(3):

Mitochondrial Impairment in Unloaded Postural Muscle: Mechanisms Driving Loss of Muscle Function and Mass.

Kristina A Sharlo, Timur M Mirzoev, Boris S Shenkman.

  Mechanical unloading of skeletal muscle triggers various signaling alterations that result in muscle atrophy and weakness. Mitochondria are essential to muscle health, acting not only as energy suppliers but also as central mediators of molecular regulation. Mitochondrial activity, content, and dynamics are tightly controlled by multiple signaling pathways; conversely, mitochondria-derived messengers, such as reactive oxygen species (ROS), ATP, and mitokines, are involved in the regulation of nearly all aspects of muscle signaling. During mechanical unloading, altered muscle activity leads to mitochondrial dysfunction. However, the initial triggers, underlying mechanisms, and full consequences of this dysfunction remain poorly understood. Nevertheless, mitochondria-targeted therapies have emerged as a promising strategy for mitigating unloading-induced muscle impairments. In this review, we summarize current data regarding the characteristics, causes, and outcomes of unloading-induced mitochondrial dysfunction, specifically focusing on muscle atrophy and functional decline. We highlight novel findings regarding the roles of mitokines and mitochondrial calcium overload, propose a new hypothesis to explain the biphasic dynamics of ATP accumulation during slow-type muscle unloading, and describe emerging therapeutic strategies to counteract these mitochondrial impairments.

Keywords:  ATP; ROS; calcium handling; dry immersion; hindlimb suspension; mechanical unloading; mitochondria; mitokines; muscle atrophy; skeletal muscle

DOI:  https://doi.org/10.3390/antiox15030277
Chronobiol Int. 2026 Mar 26. 1-6

People over 60 feel younger in the morning: A good time of day to enhance wellbeing?

Stephen P Badham, Miriam Sang-Ah Park, Aparna Nair, Fran Pilkington-Cheney.

  There is a global push to develop interventions to support older adults, but their receptiveness to adapt their behaviour may depend on changes in their alertness and wellness throughout the day. In a sample of 86 participants over 60 y old from the UK, measures of positive ageing, subjective age (e.g. how old do you feel?), daytime sleepiness, and need for cognitive closure (NFC, representing receptiveness to change) were taken at optimal and non-optimal times of day based on participants' responses to a chronotype questionnaire (the Morningness-Eveningness Questionnaire). Relative to the evening, participants felt younger in the morning and less sleepy, but reported similar levels of positivity about ageing and NFC at both time points. Although NFC did not change throughout the day, it was related to sleepiness such that participants who were sleepier may have been less receptive to change. Our sample was largely morning types in line with existing literature on older adults' chronotypes. Relative to evening, morning time may be related to feeling more alert, less sleepy and younger, and may be a generally more positive time for older adults. This highlights the potential to time the delivery of age-related interventions to maximise older adults' wellbeing.

Keywords:  Subjective age; chronotype; intervention; morningness-eveningness questionnaire; sleepiness

DOI:  https://doi.org/10.1080/07420528.2026.2648753