Aging skeletal muscle shows impaired mitochondrial function, altered redox regulation, disrupted fusion-fission balance, and reduced mitochondrial turnover. This translational systematic synthesis and meta-analysis evaluated whether exercise training remodels mitochondrial and functional outcomes in aging muscle. PubMed, EMBASE, and Web of Science were searched to June 26, 2026 following PRISMA 2020. Twenty-eight studies involving aged exercise groups compared to sedentary groups were included. Outcomes covered oxidative stress, mitochondrial dynamics, mitophagy, mitochondrial biogenesis/function, skeletal muscle morphology, and physiological performance. Random-effects meta-analysis showed a significant improvement in VO2max/VO2peak after exercise training (SMD = 0.46, p < 0.001; I[2] = 0%), whereas pooled changes in citrate synthase (SMD = 0.18, p = 0.450) and BMI (SMD = -0.09, p = 0.557) were not significant. The directional synthesis showed that mitochondrial biogenesis and function were consistently responsive across species, particularly for OXPHOS proteins, mitochondrial volume density, ATPmax, and SIRT1/SIRT3 signaling. Human and rodent studies assessed different, only partly overlapping mitophagy and mitochondrial dynamics markers. Therefore, differences in pathway responsiveness across species cannot be separated from differences in which markers were measured. Exercise training and lifelong physical activity were associated with changes in mitochondrial biogenesis, dynamics, mitophagy-related signaling, and muscle function in aging skeletal muscle. The observed patterns varied by training protocol and study design, but indirect comparisons and heterogeneous outcome measures preclude conclusions about the superiority of any modality. Human and rodent findings should therefore be interpreted as complementary evidence rather than equivalent estimates of biological response.

Mallory-Denk bodies (MDBs), a hallmark pathological feature of metabolic dysfunction-associated steatotic liver disease (MASLD), have been associated with hepatocellular senescence; however, the underlying regulatory mechanisms remain incompletely understood. We investigated whether the transforming growth factor-β (TGF-β)/p38 mitogen-activated protein kinase (p38 MAPK) signaling axis serves as a shared regulatory pathway driving both MDB formation and hepatocellular senescence. To address this, we established two MDB-positive mouse models: a metabolic dysfunction-associated steatohepatitis (MASH) model induced by a high-fat diet (HFD) combined with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and a liver fibrosis model induced by carbon tetrachloride (CCl4) plus DDC. These were complemented by an in vitro MDB-forming hepatocyte model stimulated with TNF-α/IFN-γ and TGF-β. In addition, three clinical hepatocellular carcinoma (HCC) specimens with abundant MDBs were analyzed. Multiplex immunofluorescence, RNA sequencing (RNA-seq), and functional in vitro and in vivo assays were employed. Both animal models consistently exhibited MDB formation, metabolic dysregulation, and liver fibrosis, accompanied by activation of p38 signaling, increased phosphorylation of keratin 8 at serine 73 (p-K8 S73), and features of hepatocellular senescence. RNA-seq analysis of the HFD+DDC-induced MASH model further implicated p38 signaling in MDB formation and cellular senescence at the transcriptomic level. Activation of p38 signaling was also confirmed in human HCC specimens. In vitro, pharmacological inhibition of p38 reduced p-K8 S73 levels, suppressed MDB formation, and attenuated the senescent phenotype. Collectively, these findings suggest the TGF-β/p38 signaling axis may be a common molecular mechanism underlying both MDB formation and hepatocellular senescence, providing new insights into the pathogenesis of MDB-associated liver diseases.

Social isolation and loneliness significantly affect the physical and mental health of older adults, contributing to cognitive decline, increased morbidity, and reduced quality of life. Addressing these conditions remains a public health priority, prompting the continued development and evaluation of interventions to reduce their impact. This umbrella review aimed to identify, synthesise and critically appraise the existing evidence on interventions aimed at reducing social isolation and loneliness among community-dwelling older adults. Following PRISMA guidelines, a systematic search of systematic reviews, scoping reviews, and meta-analyses published between 2014 and 2025 was conducted in PsycINFO, Scopus, Web of Science and PubMed. The search identified 2068 records, of which 28 met the inclusion criteria and quality assessment. A narrative synthesis was conducted to categorise the interventions based on objectives and delivery formats. Five types of interventions were identified: psychosocial, technological, health promotion, multicomponent, and recreational. Psychosocial approaches, complemented by technology or structured leisure activities, appear most effective, particularly when they foster meaningful relationships and enhance coping strategies. Findings suggest that interventions targeting social isolation and loneliness can meaningfully enhance the wellbeing of older adults and should be integrated into community and healthcare service models. However, further research is needed to assess the long-term effects of these interventions, their cost-effectiveness, and their feasibility for large-scale implementation across diverse ageing populations.

Adult loneliness has been linked to various age-related conditions, yet the long-term consequences of childhood loneliness remain poorly understood. This study examined the association between childhood loneliness and frailty progression in mid-to-late adulthood.