The dermis is primarily composed of the extracellular matrix (ECM) and fibroblasts. During the aging process, the dermis undergoes significant changes. Collagen, which is a major component of ECM, becomes fragmented and coarsely distributed, and its total amount decreases. This is mainly due to increased activity of matrix metalloproteinases, and impaired transforming growth factor-β signaling induced by reactive oxygen species generated during aging. The reduction in the amount of collagen hinders the mechanical interaction between fibroblasts and the ECM, and consequently leads to the deterioration of fibroblast function and further decrease in the amount of dermal collagen. Other ECM components, including elastic fibers, glycosaminglycans (GAGs), and proteoglycans (PGs), also change during aging, ultimately leading to a reduction in the amount of functional components. Elastic fibers decrease in intrinsically aged skin, but accumulate abnormally in photoaged skin. The changes in the levels of GAGs and PGs are highly diverse, and previous studies have reported conflicting results. A reduction in the levels of functional dermal components results in the emergence of clinical aging features, such as wrinkles and reduced elasticity. Various antiaging approaches, including topicals, energy-based procedures, and dermal fillers, can restore the molecular features of dermal aging with clinical efficacy. This review summarizes the current understanding of skin aging at the molecular level, and associated treatments, to put some of the new antiaging technology that has emerged in this rapidly expanding field into molecular context.

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)1,2. These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low frequency coding variants with large effects on LOAD risk, we performed whole exome-sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large case-control datasets. A rare variant in PLD3 (phospholipase-D family, member 3, rs145999145; V232M) segregated with disease status in two independent families and doubled risk for AD in seven independent case-control series (V232M meta-analysis; OR= 2.10, CI=1.47-2.99; p= 2.93×10-5, 11,354 cases and controls of European-descent). Gene-based burden analyses in 4,387 cases and controls of European-descent and 302 African American cases and controls, with complete sequence data for PLD3, indicate that several variants in this gene increase risk for AD in both populations (EA: OR= 2.75, CI=2.05-3.68; p=1.44×10-11, AA: OR= 5.48, CI=1.77-16.92; p=1.40×10-3). PLD3 is highly expressed in brain regions vulnerable to AD pathology, including hippocampus and cortex, and is expressed at lower levels in neurons from AD brains compared to control brains (p=8.10×10-10). Over-expression of PLD3 leads to a significant decrease in intracellular APP and extracellular Aβ42 and Aβ40, while knock-down of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a two-fold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may be used to identify rare variants with large effects on risk for disease or other complex traits.

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The Ca 2؉ signal is essential for the activation of plant defense responses, but downstream components of the signaling pathway are still poorly defined. Here we demonstrate that specific calmodulin (CaM) isoforms are activated by infection or pathogen-derived elicitors and participate in These results suggest that specific CaM isoforms are components of a SA-independent signal transduction chain leading to disease resistance.

Management of melasma is highly challenging due to inconsistent treatment results and frequent relapses. However, recent studies revealed that melasma may not only be a disease of melanocytes, but also a photoaging skin disorder. Herein, we attempt to validate that melasma is indeed a photoaging disorder by presenting the histopathologic findings of melasma: solar elastosis, altered basement membrane, increased vascularization and increased mast cell count. We also provide some therapeutic implications based on these findings and a discussion on the latest updates and perspectives regarding treatment.

SummaryHutchinson–Gilford progeria syndrome (HGPS), a fatal premature aging disease, is caused by a single‐nucleotide mutation in the LMNA gene. Previous reports have focused on nuclear phenotypes in HGPS cells, yet the potential contribution of the mitochondria, a key player in normal aging, remains unclear. Using high‐resolution microscopy analysis, we demonstrated a significantly increased fraction of swollen and fragmented mitochondria and a marked reduction in mitochondrial mobility in HGPS fibroblast cells. Notably, the expression of PGC‐1α, a central regulator of mitochondrial biogenesis, was inhibited by progerin. To rescue mitochondrial defects, we treated HGPS cells with a mitochondrial‐targeting antioxidant methylene blue (MB). Our analysis indicated that MB treatment not only alleviated the mitochondrial defects but also rescued the hallmark nuclear abnormalities in HGPS cells. Additional analysis suggested that MB treatment released progerin from the nuclear membrane, rescued perinuclear heterochromatin loss and corrected misregulated gene expression in HGPS cells. Together, these results demonstrate a role of mitochondrial dysfunction in developing the premature aging phenotypes in HGPS cells and suggest MB as a promising therapeutic approach for HGPS.

Vascularization is among the top challenges that impede the clinical application of engineered tissues. This challenge has spurred tremendous research endeavor, defined as vascular tissue engineering (VTE) in this article, to establish a pre-existing vascular network inside the tissue engineered graft prior to implantation. Ideally, the engineered vasculature can be integrated into the host vasculature via anastomosis to supply nutrient to all cells instantaneously after surgery. Moreover, sufficient vascularization is of great significance in regenerative medicine from many other perspectives. Due to the critical role of vascularization in successful tissue engineering, we aim to provide an up-to-date overview of the fundamentals and VTE strategies in this article, including angiogenic cells, biomaterial/bio-scaffold design and bio-fabrication approaches, along with the reported utility of vascularized tissue complex in regenerative medicine. We will also share our opinion on the future perspective of this field.

This study aimed to compare health-related quality of life (HRQOL) over time in patients initiating hemodialysis (HD) or peritoneal dialysis (PD). A total of 989 incident patients starting HD or PD were included from a prospective nationwide cohort study. HRQOL was assessed 3, 12, and 24 months after the start of dialysis. The scores of questionnaires were adjusted for clinical and socioeconomic parameters. The adjusted three months scores of patients on PD showed better HRQOL in eight end-stage renal disease (ESRD), three physical component summary and one mental component summary domains compared with patients on HD. Both patients on HD and PD experienced significant decreases in different HRQOL domains over two years and the degree of changes in HRQOL over time was not different between dialysis modality. However, the scores of three (effects of kidney disease, burden of kidney disease, and dialysis staff encouragement, all P < 0.05) and two (sexual function and dialysis staff encouragement, all P < 0.05) ESRD domains were still higher in patients on PD compared with patients on HD at one and two years after initiation of dialysis, respectively. PD shows better HRQOL during the initial period after dialysis even after adjusting for clinical and socioeconomic characteristics, and the effect lasts up to two years. It was similar in terms of changes in HRQOL over time between HD and PD.