Star fruit extract and C-glycosylated flavonoid components have potential to prevent air pollutant-induced skin inflammation and premature aging

Air pollution adversely affects skin,leading to skin inflammation and premature skin aging.Plant derived antioxidant compounds have been considered to be promising in discovery of effective agents for the protection of skin from the damage by air pollutants.Our previous studies demonstrated that Averrhoa carambola fruit(known as star fruit)is rich in flavonoid C-glycosides with unique structures and potent antioxidant activity.Thus,the star fruit extract(SFE)and main flavonoid C-glycoside components,carambolasides I,J,and P(1-3),carambolaflavone B(4),and isovitexin 2″-O-α-l-rhamnoside(5),were investigated for the activity against air pollutant stress in human epidermis.As a result,SFE and compounds 1-5 exhibited significant inhibitory activity against protein carbonylation in oxidative-stressed stratum corneum with the best activity being shown by compound 3.SFE and compounds 2-5 were also active against engine exhaust-induced protein carbonylation in stratum corneum.When further evaluated,SFE and com-pound 3 significantly inhibited gene expression of the key inflammation mediators IL-1αand COX-2 in PM-stressed keratinocytes.The results indicated that SFE and the flavonoid C-glycosides are potentially effective against air pollutant-induced skin inflammation and premature aging.

Skeletal phenotypes and molecular mechanisms in aging mice

Aging is an inevitable physiological process,often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks.Research on skeletal diseases caused by aging in humans is challenging due to lengthy study durations,difficulties in sampling,regional variability,and substantial investment.Consequently,mice are preferred for such studies due to their similar motor system structure and function to humans,ease of handling and care,low cost,and short generation time.In this review,we present a comprehensive overview of the characteristics,limitations,applicability,bone phenotypes,and treatment methods in naturally aging mice and prematurely aging mouse models(including SAMP6,POLG mutant,LMNA,SIRT6,ZMPSTE24,TFAM,ERCC1,WERNER,and KL/KL-deficient mice).We also summarize the molecular mechanisms of these aging mouse models,including cellular DNA damage response,senescence-related secretory phenotype,telomere shortening,oxidative stress,bone marrow mesenchymal stem cell(BMSC)abnormalities,and mitochondrial dysfunction.Overall,this review aims to enhance our understanding of the pathogenesis of aging-related bone diseases.

SIRTain regulators of premature senescence and accelerated aging

The sirtuin proteins constitute class III histone deacetylases （HDACs）. These evolutionarily conserved NAD＋-dependent enzymes form an important component in a variety of cellular and biological processes with highly divergent as well as convergent roles in maintaining metabolic homeostasis, safeguarding genomic integrity, regulating cancer metabolism and also inflammatory responses. Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in pro- moting longevity and ameliorating age-associated pathologies. The contributions of other sirtuins in the field of aging are also gradually emerging. Here, we summarize some of the recent discoveries in sirtuins biology which clearly implicate the functions of sirtuin proteins in the regulation of premature cellular senescence and accelerated aging. The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms. Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.

Lamin C protein deficiency in the primary fibroblasts from a new laminopathy case with ovarian cystadenoma

Background Laminopathies are a group of rare genetic disorders characterized by multiple-tissue degeneration.We describe a new laminopathy with ovarian cystadenoma and explore its molecular etiology.Methods The case is a 15-year-old girl who presents the prominent progeroid disorders, multiple system degeneration and early-onset cystadenoma of the ovary.Candidate genes including LMNA, ZMPSTE24, PPAR G, INSR and WRN were sequenced to screen for DNA variants.The mRNA and protein expression levels of LMNA were examined in primary fibroblasts.The pathophysiological events such as morphologic alterations, cell senescence, cell proliferation,apoptosis and pRb as well as p53 protein expressions were also investigated in primary fibroblasts.Results No mutation was identified in the candidate genes screened.Nuclear abnormalities including nuclear blebs,mislocalization of lamin A/C were evident in the patient fibroblasts.Ultrastructurally, nucleus exhibited nuclear herniation and almost complete loss of peripheral heterochromatin.In addition, lamin C protein expression was markedly reduced whereas lamin A protein level was normal and no prelamin A was detected in the primary fibroblasts.Although the senescence-associated β-galactosidase staining of patient＇ cells was negative, cells in S phase increased in accompany with a decrease in pRb protein expression.Furthermore, increases in apoptotic cell death and p53 expression were observed.Conclusions Our data suggest that selective deficiency of lamin C protein is associated with a case of laminopathy with ovarian cystadenoma.The abnormalities in nuclear structure and alterations in gene expression such as the decrease in pRb and increase in p53 may be responsible for the multiple tissue degeneration.