Environmental exposure to heavy metals seriously threatens children’s health, potentially impacting the cardiovascular system. Mechanisms such as oxidative stress, inflammation, and lipid metabolism disturbances play a significant role in this process. Although cardiovascular diseases typically manifest in adulthood, an increasing number of studies suggest that their origins trace back to childhood and result from long-term pathophysiological changes. Therefore, early identification of modifiable risk factors is crucial for effective preventive measures and reducing future health risks.

Ischemic stroke accounts for approximately 80–85% of all stroke cases and triggers a complex cascade of metabolic, immunological, and neurodegenerative processes. Among the key mediators involved, TNF-α occupies a central position due to its distinctly dual and phase-dependent actions. Importantly, the biological effects of TNF-α are not static but evolve dynamically over time following ischemic insult. During the acute phase of ischemia, a rapid increase in TNF-α levels, primarily originating from activated microglia, leads to the predominant activation of the TNFR1 receptor. This results in enhanced apoptosis and necroptosis, disruption of the blood–brain barrier, increased leukocyte recruitment, and the progression of secondary neuronal injury. In later phases, the role of TNF-α shifts, with signaling through TNFR2 becoming more prominent, thereby supporting reparative mechanisms, including neurogenesis, angiogenesis, and synaptic remodeling. The dual nature of TNF-α means that both its excessive activation and complete inhibition may produce detrimental effects. Notably, the therapeutic relevance of TNF-α critically depends on the timing of intervention relative to stroke onset. A comprehensive analysis of current evidence underscores the central, temporally and contextually dependent role of TNF-α in the pathophysiology of ischemic stroke. It also indicates that future therapeutic strategies should aim to selectively suppress the harmful TNFR1-mediated signaling while preserving or enhancing TNFR2-dependent neuroprotective pathways. Such time-sensitive and receptor-selective modulation holds promise for limiting acute ischemic injury and promoting endogenous repair processes, representing a compelling direction for the development of next-generation neuroprotective therapies.

Ischemic stroke triggers a severe redox disequilibrium that critically shapes cell survival within the penumbra. Although oxidative DNA damage arises from excessive ROS production, the capacity to repair such lesions is tightly constrained by cellular metabolic status. Growing evidence indicates that astrocytes, key metabolic regulators of the neurovascular unit, modulate neuronal susceptibility to genomic injury through redox buffering, NAD⁺ maintenance, and metabolic support. In the metabolically impaired yet structurally preserved penumbra, astrocytic control of glutathione turnover, mitochondrial function, and lactate shuttling may determine whether oxidative DNA lesions are efficiently repaired or progress toward energetic collapse. Poly(ADP-ribose) polymerase 1 activation following DNA strand breaks couples genomic stress to NAD⁺ depletion and bioenergetic failure, forming a critical interface between redox biology and metabolism. This framework posits that astrocytes preserve genomic integrity not by directly altering DNA repair pathways but by sustaining the energetic capacity required for an effective DNA damage response. Elucidating this astrocyte-centered redox–metabolic axis may reveal therapeutic strategies to stabilize penumbral tissue and improve stroke outcomes.

Skeletal muscle retains adaptive information from previous mechanical loading, enabling faster responses to subsequent training and regenerative challenges. This review synthesizes current evidence on the cellular and epigenetic mechanisms underlying skeletal muscle memory and examines how these mechanisms are modified by aging and post-injury regeneration. Muscle memory emerges from complementary structural and molecular components, including myonuclear retention, persistent DNA methylation changes, chromatin remodeling, transcriptional priming, non-coding RNA regulation, and mitochondrial epigenetic adaptations. These mechanisms interact with muscle satellite cells (MuSCs), fibro-adipogenic progenitors (FAPs), immune cells, and extracellular matrix remodeling to maintain regenerative competence. During aging, epigenetic drift, chronic low-grade inflammation, altered macrophage states, MuSC dysfunction, persistent FAP activity, fibrosis, mitochondrial impairment, and anabolic resistance progressively reduce this plasticity, thereby contributing to sarcopenia. Training–detraining–retraining studies indicate that parts of the exercise-induced epigenetic landscape remain detectable after training cessation and can be reactivated during renewed loading, although the persistence and functional importance of individual molecular signatures remain incompletely defined. Physical exercise remains the most established intervention for preserving muscle function and epigenetic responsiveness, whereas caloric restriction, modulation of nutrient-sensing pathways, senolytic strategies, and direct targeting of epigenetic regulators remain promising but translationally less mature approaches. Overall, the preservation of epigenetic plasticity may be a key determinant of healthy skeletal muscle aging and effective regeneration.