Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing

Cellular senescence is now considered as a major mechanism in the development and progression of various diseases and this may include metabolic diseases such as obesity and type-2 diabetes. The presence of obesity and diabetes is a major risk factor in the development of additional health conditions, such as cardiovascular disease, kidney disease and cancer. Since senescent cells can drive disease development, obesity and diabetes can potentially create an environment that accelerates cell senescence within other tissues of the body. This can consequently manifest as age-related biological impairments and secondary diseases. Cell senescence in cell types linked with obesity and diabetes, namely adipocytes and pancreatic beta cells will be explored, followed by a discussion on the role of obesity and diabetes in accelerating ageing through induction of premature cell senescence mediated by high glucose levels and oxidised low-density lipoproteins. Particular emphasis will be placed on accelerated cell senescence in endothelial progenitor cells, endothelial cells and vascular smooth muscle cells with relation to cardiovascular disease and proximal tubular cells with relation to kidney disease. A summary of the potential strategies for therapeutically targeting senescent cells for improving health is also presented

Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Cellular senescence is now considered as a major mechanism in the development and progression of various diseases and this may include metabolic diseases such as obesity and type-2 diabetes. The presence of obesity and diabetes is a major risk factor in the development of additional health conditions, such as cardiovascular disease, kidney disease and cancer. Since senescent cells can drive disease development, obesity and diabetes can potentially create an environment that accelerates cell senescence within other tissues of the body. This can consequently manifest as age-related biological impairments and secondary diseases. Cell senescence in cell types linked with obesity and diabetes, namely adipocytes and pancreatic beta cells will be explored, followed by a discussion on the role of obesity and diabetes in accelerating ageing through induction of premature cell senescence mediated by high glucose levels and oxidised low-density lipoproteins. Particular emphasis will be placed on accelerated cell senescence in endothelial progenitor cells, endothelial cells and vascular smooth muscle cells with relation to cardiovascular disease and proximal tubular cells with relation to kidney disease. A summary of the potential strategies for therapeutically targeting senescent cells for improving health is also presented

Senescence in the aging process.

The accumulation of 'senescent' cells has long been proposed to act as an ageing mechanism. These cells display a radically altered transcriptome and degenerative phenotype compared with their growing counterparts. Tremendous progress has been made in recent years both in understanding the molecular mechanisms controlling entry into the senescent state and in the direct demonstration that senescent cells act as causal agents of mammalian ageing. The challenges now are to gain a better understanding of how the senescent cell phenotype varies between different individuals and tissues, discover how senescence predisposes to organismal frailty, and develop mechanisms by which the deleterious effects of senescent cells can be ameliorated

A facile, stereoselective, one-pot synthesis of resveratrol derivatives

BACKGROUND: Compounds based on trans-1,2-diphenylethene are the subject of intense interest both for their optical properties and as potential leads for drug discovery, as a consequence of their anticancer, anti-inflammatory and antioxidant properties. Perhaps the best known of these is trans-3,5,4′-trihydroxystilbene (resveratrol), that has been identified as a promising lead in the search for anti-ageing therapeutics. RESULTS: We report here a new, convenient, one-pot stereo-selective synthesis of resveratrol and other trans-stilbene derivatives. A wide range of known and novel “Resveralogues” were synthesised by using this simple protocol, including examples with electron donating and electron withdrawing substituents, in uniformly high yield. The structures of all compounds were confirmed by standard methods including (1)H and (13)C NMR, IR and High Resolution Mass spectroscopy. CONCLUSIONS: We have established a simple and convenient protocol for resveralogue synthesis. It is readily scalable, and sufficiently robust and simple for ready use in automated synthesis or for library development of resveralogues. This supersedes previously reported synthetic methods that required inert conditions, extensive purification and/or costly reagents. [Figure: see text

Telomere-based proliferative lifespan barriers in Werner-syndrome fibroblasts involve both p53-dependent and p53-independent mechanisms

Werner-syndrome fibroblasts have a reduced in vitro life span before entering replicative senescence. Although this has been thought to be causal in the accelerated ageing of this disease, controversy remains as to whether Werner syndrome is showing the acceleration of a normal cellular ageing mechanism or the occurrence of a novel Werner-syndrome-specific process. Here, we analyse the signalling pathways responsible for senescence in Werner-syndrome fibroblasts. Cultured Werner-syndrome (AG05229) fibroblasts senesced after approximately 20 population doublings with most of the cells having a 2N content of DNA. This was associated with hypophosphorylated pRb and high levels of p16(Ink4a) and p21(Waf1). Senescent AG05229 cells re-entered the cell cycle following microinjection of a p53-neutralizing antibody. Similarly, production of the human papilloma virus 16 E6 oncoprotein in presenescent AG05229 cells resulted in senescence being bypassed and extended cellular life span. Werner-syndrome fibroblasts expressing E6 did not proliferate indefinitely but reached a second proliferative lifespan barrier, termed M(int), that could be bypassed by forced production of telomerase in post-M1 E6-producing cells. The conclusions from these studies are that: (1) replicative senescence in Werner-syndrome fibroblasts is a telomere-induced p53-dependent event; and (2) the intermediate lifespan barrier M(int) is also a telomere-induced event, although it appears to be independent of p53. Werner-syndrome fibroblasts resemble normal human fibroblasts for both these proliferative lifespan barriers, with the strong similarity between the signalling pathway linking telomeres to cell-cycle arrest in Werner-syndrome and normal fibroblasts providing further support for the defect in Werner syndrome causing the acceleration of a normal ageing mechanism

Bird responses to targeted revegetation : 40 years of habitat enhancement at Clarkesdale Bird sanctuary, central-western Victoria

A program of planting Australian shrubs and trees has been conducted in degraded farmland at the Clarkesdale Bird Sanctuary (central-western Victoria) since the 1960s, to address the issue of declining native birds, as perceived by the late landowner Gordon Clarke. The shrubs and trees were selected to attract birds, and included many species that were not native to the region. This form of management is often practised by private landholders (at various scales), but its effects are rarely documented. Bird surveys were conducted for this study between 1999 and 2001 at 27 sites: 11 in native eucalypt forest on ridges and slopes, 13 in planted areas on ridges and slopes, and three in planted areas on river-flats and a small gully (with three supplementary sites in a pine plantation). Total bird abundance and species per count were highest in the planted sites on river-flats and gully, and higher in the planted sites on ridges and slopes than in native forest on similar topography. Honeyeaters (Meliphagidae), Superb Fairy-wrens Malurus cyaneus, open-country birds, seed-eating birds and five insectivorous guilds reached their maximum abundance in planted sites. Barkforaging insectivores, canopy-foraging insectivores, frugivores and a generalist insectivore were marginally more common in native forest than in planted sites. Introduced birds were uncommon. Generalised linear modelling showed that total bird abundance was positively related to the cover of planted native vegetation, native low shrubs and young wattles Acacia spp. and to the presence of indigenous Cherry Ballart Exocarpos cupressiformis. Various guilds showed positive relationships with the cover of planted native vegetation, native low shrubs, young wattles, original old wattles, original old eucalypts and trees with small or large hollows. The planting program has provided new habitat for many native forest birds. A greater challenge is to address the needs of some uncommon species that have declined locally, such as the Brown Treecreeper Climacteris picumnus and Speckled Warbler Chthonicola sagittata

Total carotenoid content, α-carotene and β-carotene, of landrace pumpkins (Cucurbita moschata Duch): A preliminary study

AbstractLandrace pumpkins occur in nature and their potential as source of pro-vitamin A may be investigated in order to be used in conventional plant breeding or biofortification programs, aiming to increase the total carotenoids and β-carotene contents. The objective of the study was to determine the total carotenoid, α-carotene, β-carotene and its isomers and contents in two landrace samples (A and B) of raw pumpkins (Cucurbita moschata) to verify its seed production potential. High Performance Liquid Chromatography and UV/Visible spectrophotometry were used to determine α-carotene, β-carotene and its isomers, and total carotenoid contents, respectively. All analyses were carried out in triplicate. The results showed mean total carotenoid contents of 404.98 in sample A, and 234.21μg/g in sample B. The α-carotene contents varied from 67.06 to 72.99μg/g in samples A and B, respectively. All E-β-carotene was the most abundant isomer found varying from 244.22 to 141.95μg/g in samples A and B, respectively. The 9 and 13-Z-β-carotene isomers were still found in low concentrations in both analyzed landrace samples. The content of β-carotene in raw sample A showed to be promising for the production of seeds for cultivation and consumption