Ageing generates senescent pathologies, some of which cause death. Interventions that delay or prevent lethal pathologies will extend lifespan. Here we identify life-limiting pathologies in Caenorhabditis elegans with a necropsy analysis of worms that have died of old age. Our results imply the presence of multiple causes of death. Specifically, we identify two classes of corpse: early deaths with a swollen pharynx (which we call ‘P deaths'), and later deaths with an atrophied pharynx (termed ‘p deaths'). The effects of interventions on lifespan can be broken down into changes in the frequency and/or timing of either form of death. For example, glp-1 mutation only delays p death, while eat-2 mutation reduces P death. Combining pathology and mortality analysis allows mortality profiles to be deconvolved, providing biological meaning to complex survival and mortality profiles.

In model organisms, over 2,000 genes have been shown to modulate aging, the collection of which we call the ‘gerontome’. Although some individual aging-related genes have been the subject of intense scrutiny, their analysis as a whole has been limited. In particular, the genetic interaction of aging and age-related pathologies remain a subject of debate. In this work, we perform a systematic analysis of the gerontome across species, including human aging-related genes. First, by classifying aging-related genes as pro- or anti-longevity, we define distinct pathways and genes that modulate aging in different ways. Our subsequent comparison of aging-related genes with age-related disease genes reveals species-specific effects with strong overlaps between aging and age-related diseases in mice, yet surprisingly few overlaps in lower model organisms. We discover that genetic links between aging and age-related diseases are due to a small fraction of aging-related genes which also tend to have a high network connectivity. Other insights from our systematic analysis include assessing how using datasets with genes more or less studied than average may result in biases, showing that age-related disease genes have faster molecular evolution rates and predicting new aging-related drugs based on drug-gene interaction data. Overall, this is the largest systems-level analysis of the genetics of aging to date and the first to discriminate anti- and pro-longevity genes, revealing new insights on aging-related genes as a whole and their interactions with age-related diseases.

Purpose To investigate the effect of OK lens treatment zone decentration on myopia control. Methods We retrospectively selected 30 OK lens wearers who met the following conditions in our hospital from more than 1300 cases: wearing lens in both eyes and only one eye was off-center while the other one was centric for more than 12 months. During the period of follow-up, the UCVA of each eye was better than 0.1 of logMAR and there were no obvious tropia, Kappa angle, and complications such as glare and diplopia. Result Among 30 cases, 15 are males and 15 are females, with an average age of 9.3 ± 1.51Y. There were no significant differences in equivalent spherical lens, astigmatism, e value, flat K, steep K, astigmatism, lens diameter, and toric between the two groups (p > 0.05). The average distance of decentration was 0.73 ± 0.25 mm. Axis growth per year in was 0.20 ± 0.24 mm the OK-lens-decentered group and 0.29 ± 0.20 mm in the OK-lens-centric group, which shows significant difference between them (p < 0.05). According to the direction of decentration, 30 decentered eyes were divided into temporal group (20 eyes) and other direction group (10 eyes). The efficiency of myopia control (the growth of AL per year in OK-lens-decentered eye/the growth of AL per year in the contralateral OK-lens-centric eye) was 0.69 ± 0.50 in the temporal decentration group and 0.75 ± 0.52 in the other direction group, showing no significant difference between them (p > 0.05). There was no significant correlation between the efficiency of myopia control and the degree of decentration among temporal decentration group (p > 0.05). Conclusion This self-control study without much interference factors shows that the decentration of OK lens can delay the development of myopia more effectively than being centric when uncorrected visual acuity was acceptable without obvious corneal complications, glare, or ghosting.

Posttraumatic stress disorder (PTSD) is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription factor NF-κB in the different phases of memory. Here, we demonstrate that inhibition of NF-κB in the basolateral amygdala (BLA), but not central nucleus of the amygdala, after memory reactivation impairs the retention of amygdala-dependent auditory fear conditioning (AFC). We used two independent pharmacological strategies to disrupt the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an inhibitor of IκB kinase that activates NF-κB, and bilateral intra-BLA infusion of SN50, a direct inhibitor of the NF-κB DNA-binding complex, immediately after retrieval disrupted the reconsolidation of AFC. We also found that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor that enhances histone acetylation, in the amygdala rescued the disruption of reconsolidation induced by NF-κB inhibition in the BLA. These findings indicate that NF-κB activity in the BLA is required for memory reconsolidation in AFC, suggesting that NF-κB might be a potential pharmacotherapy target for posttraumatic stress disorder.