The ongoing COVID-19 pandemic is caused by an RNA virus, SARS-CoV-2. The genome of SARS-CoV-2 lacks a nuclear phase in its life cycle and is replicated in the cytoplasm. However, interfering with nuclear trafficking using pharmacological inhibitors greatly reduces virus infection and virus replication of other coronaviruses is blocked in enucleated cells, suggesting a critical role of the nucleus in virus infection. Here, we summarize the alternations of nuclear pathways caused by SARS-CoV-2, including nuclear translocation pathways, innate immune responses, mRNA metabolism, epigenetic mechanisms, DNA damage response, cytoskeleton regulation, and nuclear rupture. We consider how these alternations contribute to virus replication and discuss therapeutic treatments that target these pathways, focusing on small molecule drugs that are being used in clinical studies.

In migratory fibroblasts, front-rear polarity is defined by the centrosome positioned anterior to a rearward nucleus. To achieve this polarity, actin cables couple to nuclear membrane proteins nesprin-2G and SUN2 and drive the nucleus backward. Aging disrupts this polarity by increasing SUN1, a SUN2 homolog. Here, we investigated the molecular mechanisms behind this disruption and found that the dominant-negative effect of SUN1 and progerin, a lamin A variant, required direct SUN1-lamin A interaction. Microtubule interaction and force transmission through a nesprin, identified as nesprin-2, are crucial for SUN1’s effect. We further discovered that stable microtubules are both necessary and sufficient to inhibit cell polarity. Using SUN1-SUN2 chimeric proteins, we demonstrated that the SUN domains determine their roles in cell polarization. Our findings reveal how elevated SUN1 disrupts cell polarity through coupling microtubules and nuclear lamina, emphasizing the impact of altered microtubule stability and nuclear mechanotransduction in polarity defects.

Cysteine is an amino acid present in thiol proteins and often dictates their secondary structures. Although considered nonessential, cysteine may be essential for patients with certain metabolic diseases and can reduce the requirement for dietary methionine. Cysteine and some of its derivatives, such as N‐acetylcysteine, are considered antioxidants and widely used in animal aging studies. To provide insights into the potential anti‐aging effects of cysteine, we systematically reviewed and performed a meta‐analysis to investigate the impact of cysteine supplementation on lifespan using three model organisms: mice, nematodes, and fruit flies. A total of 13 mouse studies, 13 C. elegans studies, and 5 Drosophila studies were included in the analysis. The findings revealed that cysteine supplementation significantly reduced the risk of mortality in mice and C. elegans. Subgroup analysis showed consistent results across different starting times and administration methods and revealed adverse effects of high doses on worms and a lack of effect in nondisease mouse models. Similar to mice, the effects of cysteine supplementation on Drosophila were not statistically significant, except in transgenic flies. The study identified certain limitations, including the quality of the included studies and the potential for publication bias. We also discussed uncertainties in the underlying molecular mechanisms and the clinical application of dietary cysteine.

Ovarian endometriosis (OEM) is a chronic inflammatory condition that impairs ovarian function. While its effects on ovarian reserve are well established, the long-term consequences of OEM on ovarian dysfunction, premature ovarian failure (POF), and systemic health, particularly in the context of accelerated aging, remain insufficiently studied. In this study, we employed an OEM mouse model and bulk RNA sequencing to investigate the underlying mechanisms. Our results show that OEM accelerates primordial follicle depletion and upregulates mTOR signaling pathway gene expression, along with mechanical stress and paracrine signaling via the Hippo and Myc pathways. OEM also induces irregular estrus and ovarian fibrosis in aging mice, decreases serum AMH levels, and increases FSH levels. Systemically, elevated serum IgG levels contribute to osteoporosis and cognitive decline, both linked to ovarian dysfunction and POF in OEM. These findings elucidate the mechanisms driving premature ovarian reserve depletion in OEM and highlight its broader systemic effects. This study emphasizes the importance of monitoring ovarian health and ectopic tissue to safeguard ovarian reserves and mitigate long-term risks such as osteoporosis and cognitive decline.

During spaceflight, the female reproductive system undergoes substantial adaptation to microgravity and faces an increased risk of reproductive impairment. Mammalian oocytes remain arrested for extended periods at the first meiotic prophase, a stage particularly vulnerable to DNA damage, yet whether simulated microgravity (SMG) directly induces oocyte genomic damage and how such damage, together with the associated meiotic arrest, can be mitigated remain unclear. Melatonin (MLT), a pineal hormone with broad physiological roles, has shown benefits in improving oocyte quality in vivo and in vitro. Using SMG as a stress model, we demonstrate that during the prophase-arrested stage, SMG exposure induces DNA double-strand breaks with activation of the ATM-CHK2 DNA damage response, without detectable elevation of global cellular ROS or mitochondrial superoxide. These changes were accompanied by abnormal mitochondrial distribution and increased early apoptosis. In vitro MLT supplementation during SMG exposure alleviated DNA damage through a DNA-PKcs-associated NHEJ repair response, improved mitochondrial distribution, and this protective effect was largely independent of canonical MT1 or MT2 receptor signaling. During meiotic maturation, MLT improved SMG-induced spindle assembly defects, promoted MTOC coalescence, suppressed mitochondrial unfolded protein response overactivation, reduced SMG-induced mitochondrial hyperpolarization, and reduced early apoptosis. Consequently, oocytes exposed to MLT exhibited increased first polar body extrusion, improved spindle integrity, and enhanced oocyte-intrinsic developmental competence, as reflected by increased blastocyst formation after parthenogenetic activation. Together, these findings show that SMG induces DNA damage in prophase-arrested oocytes and identify MLT as a stage- and dose-sensitive modulator of DNA repair and mitochondrial homeostasis, offering a potential strategy to protect female reproductive health during spaceflight.