FOXO3A Plays a Role in Wound Healing by Regulating Fibroblast Mitochondrial Dynamics.

The skin plays a protective role against harmful environmental stress such as UV rays. Therefore, the skin is constantly exposed to potential injuries, and wound healing is a vital process for the survival of all higher organisms. Wound healing is dependent on aging and metabolic status at a whole-body level.

Mechanisms underlying retardation of aging by dietary energy restriction.

Moderate restriction of dietary energy intake, referred to here as dietary restriction (DR), delays aging and extends lifespan in experimental animals compared with a diet of ad libitum feeding (AL) control animals. Basic knowledge of the mechanisms underlying the effects of DR could be applicable to extending the healthspan in humans. This review highlights the importance of forkhead box O (FoxO) transcription factors downstream of the growth hormone-insulin-like growth factor 1 signaling in the effects of DR.

Itpr1 regulates the formation of anterior eye segment tissues derived from neural crest cells.

Mutations in ITPR1 cause ataxia and aniridia in individuals with Gillespie syndrome (GLSP). However, the pathogenic mechanisms underlying aniridia remain unclear. We identified a de novo GLSP mutation hotspot in the 3'-region of ITPR1 in five individuals with GLSP.

Mechanisms of Calorie Restriction: A Review of Genes Required for the Life-Extending and Tumor-Inhibiting Effects of Calorie Restriction.

This review focuses on mechanisms of calorie restriction (CR), particularly the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis as an evolutionary conserved signal that regulates aging and lifespan, underlying the effects of CR in mammals. Topics include (1) the relation of the GH-IGF-1 signal with chronic low-level inflammation as one of the possible causative factors of aging, that is, inflammaging, (2) the isoform specificity of the forkhead box protein O (FoxO) transcription factors in CR-mediated regulation of cancer and lifespan, (3) the role for FoxO1 in the tumor-inhibiting effect of CR, (4) pleiotropic roles for FoxO1 in the regulation of disorders, and (5) sirtuin (Sirt) as a molecule upstream of FoxO. From the evolutionary view, the necessity of neuropeptide Y (Npy) for the effects of CR and the pleiotropic roles for Npy in life stages are also emphasized.

Effects of rikkunshito supplementation on resistance to oxidative stress and lifespan in mice.

Aim: Caloric restriction (CR), which limits the caloric intake to 60-70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite-stimulating peptide, is essential for the anti-oxidative and life-extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR-like life-extending effects.

Identification of Specific miRNAs in Neutrophils of Type 2 Diabetic Mice: Overexpression of Accelerates Diabetic Wound Healing.

Neutrophils are involved in the first stage of acute inflammation. After injury, they are mobilized and recruited to the injured tissue. In diabetes, wound healing is delayed and aberrant, leading to excessive recruitment and retention of neutrophils that fail to promote angiogenesis and prolong inflammation.

Targeting in neutrophils enhances the clearance of in infected wounds.

Argonaute 2 bound mature microRNA (Ago2-miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation-related Ago2-miRNAs (, , , and ) and show that is critical for infection control. mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin-6 expression, and markedly improved repair of -infected wounds.

Identification and functional analysis of inflammation-related miRNAs in skin wound repair.

Inflammation at a wound site is essential for preventing infection. However, misregulated inflammation leads to pathologies of the healing process, including chronic non-healing wounds and scarring. MicroRNAs (miRNAs) are key regulators of the inflammatory response and tissue repair, acting by translational processing of target mRNAs.

Comparing the Effects of Melatonin with Caloric Restriction in the Hippocampus of Aging Mice: Involvement of Sirtuin1 and the FOXOs Pathway.

It has been suggested that age-related neurodegeneration might be associated with neuropeptide Y (NPY); sirtuin1 (SIRT1) and forkhead box transcription factors O subfamily (FOXOs) pathways. Melatonin, a hormone mainly secreted by the pineal gland, is another anti-aging agent associated with the SIRT1-FOXOs pathway. This study aimed to compare the effects of melatonin (Mel) and caloric restriction (CR) on the expression of Sirt1, FoxO1, FoxO3a and FOXOs target genes in the aging mouse hippocampus.

MiR-142 Is Required for Staphylococcus aureus Clearance at Skin Wound Sites via Small GTPase-Mediated Regulation of the Neutrophil Actin Cytoskeleton.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein translation by binding to complementary target mRNAs. We previously identified two mature members of the miR-142 family, miR-142-5p and miR-142-3p, as inflammation-related miRNAs with potential roles in wound healing. Here, we demonstrated that these two miRNAs are prominently expressed in wound-infiltrated neutrophils and macrophages and play central roles in wound healing.

Upregulation of cytochrome c oxidase subunit 6b1 (Cox6b1) and formation of mitochondrial supercomplexes: implication of Cox6b1 in the effect of calorie restriction.

Calorie restriction (CR), a non-genetic intervention that promotes longevity in animals, may exert anti-aging effects by modulating mitochondrial function. Based on our prior mitochondrial proteome analysis, we focused on the potential roles of cytochrome c oxidase (Cox or Complex IV) subunit 6b1 on formation of mitochondrial supercomplexes comprised of Complex I, III, and IV. Blue native polyacrylamide gel electrophoresis followed by immunoblotting showed that the amount of Cox6b1 and the proportion of high molecular weight supercomplexes (SCs) comprised of Complexes I, III, and IV were increased in the liver of mice subjected to 30 % CR, compared with the liver of mice fed ad libitum.

Overexpression of the adiponectin gene mimics the metabolic and stress resistance effects of calorie restriction, but not the anti-tumor effect.

Adiponectin (Adipoq), a peptide hormone secreted from the white adipose tissue, may play a role in the anti-aging and/or anti-tumor effects of calorie restriction (CR). We analyzed metabolic traits in Adipoq gene-overexpressing mice fed ad libitum with a regular diet (RD) or a high-fat diet (HFD), or fed 30% CR of RD initiated at 12 weeks of age. Adipoq-RD and -HFD mice at 6 months of age showed reduced blood glucose and insulin concentrations, and thus increased insulin sensitivity, compared with WT mice fed a RD or a HFD.