Altered growth characteristics of skin fibroblasts from wild-derived mice, and genetic loci regulating fibroblast clone size

Mouse fibroblast senescence in vitro is an important model for the study of aging at cellular level. However, common laboratory mouse strains may have lost some important allele variations related to aging processes. In this study, growth in vitro of tail skin fibroblasts (TSFs) derived from a wild-derived stock, Pohnpei (Pohn) mice, differed from growth of control C57BL/6 J (B6) TSFs. Pohn TSFs exhibited higher proliferative ability, fewer apoptotic cells, decreased expression of Cip1, smaller surface areas, fewer cells positive for senescence associated-beta-galactosidase (SA-beta-gal) and greater resistance to H(2)O(2)-induced SA-beta-gal staining and Cip1 expression. These data suggest that TSFs from Pohn mice resist cellular senescence-like changes. Using large clone ratio (LCR) as the phenotype, a quantitative trait locus (QTL) analysis in a Pohn/B6 backcross population found four QTLs for LCR: Fcs1 on Chr 3 at 55 CM; Fcs2 on Chr X at 50 CM; Fcs3 on Chr 4 at 51 CM and Fcs4 on Chr 10 at 25 CM. Together, these four QTLs explain 26.1% of the variations in LCRs in the N2 population. These are the first QTLs reported that regulate fibroblast growth. Glutathione S transferase mu (GST-mu) genes are overrepresented in the 95% confidence interval of Fcs1, and Pohn TSFs have higher H(2)O(2)-induced GST-mu 4, 5 and 7 mRNA levels than B6 TSFs. These enzymes may protect Pohn TSFs from oxidation.     

Sucrose Breakdown in Relation to Fruit Growth of Acid Lime (Citrus aurantifolia)

The physiological capacity for sucrose breakdown in developingjuice sac cells of acid limes was estimated by assaying theactivity of the three enzymes of sucrose catabolism in additionto vacuolar acid hydrolysis. The maximum potential rates ofsucrose breakdown were compared with the observed rates of carbonutilization. Highest potential rates of sucrose breakdown (28.621mmol cm^–3 per hydrated active space d^–1) occurredat the initial stages of fruit development where carbon utilizationwas highest. As the fruit developed, the potential rates ofsucrose breakdown and carbon utilization declined to very lowlevels. At 80% of development, vacuolar acid hydrolysis becamethe only physiological mechanism for sucrose breakdown. Therelatively low amounts of sucrose hydrolysed by acid hydrolysisat this time were just sufficient to account for the measuredcarbon demands. The results suggest that carbon supplied bythis distinct sucrose catabolizing system is able to provideadequate levels of carbon skeletons for the observed levelsof respiration and dry weight deposition early in development,but becomes a limiting factor for growth in the later stages. Key words: Vacuolar acid hydrolysis, Citrus aurantifolia     

Financial conflicts of interest and the ethical obligations of medical school faculty and the profession

Despite their potential benefits, relationships linking medical school faculty and the pharmaceutical and device industries may also challenge the professional value of primacy of patient welfare, a point highlighted in a recent Institute of Medicine report. Academic medical centers and professors have the added professional obligation to ensure the unbiased, evidence-based education of future doctors. This essay argues that faculty financial conflicts of interest may threaten this obligation by propagating the bias introduced by these relationships to students. This could occur directly through the process of curriculum determination and delivery, and also indirectly through the "hidden curriculum," which deserves particular attention, as its lessons may conflict with those professed in the formal curriculum. The essay concludes with guiding principles to consider when developing a conflict of interest policy at academic medical centers.     

Primate longevity: Its place in the mammalian scheme

Data on captive longevity in 587 mammalian species were analyzed in order to evaluate primate longevity in the context of general mammalian life history patterns. Contrary to some recurrent claims in the literature, we found that 1) primates are not the longest-lived mammalian order, either by absolute longevity, longevity corrected for body size, or metabolic expenditure per lifetime; 2) although relative brain size is highly correlated with longevity in primates, this is an aberrant trend for mammals in general, and other body organs account for an even greater amount of variation in longevity; and 3) there has been no progressive evolution of increased longevity among the primate superfamilies. The exceptional magnitude of primate longevity may, in keeping with evolutionary senescence theory, be due to an evolutionary history of low vulnerability to environmentally imposed death due to their body size, arboreal habit, and propensity to live in social groups. © 1992 Wiley-Liss, Inc.     

Longevity and GAPDH Stability in Bivalves and Mammals: A Convenient Marker for Comparative Gerontology and Proteostasis

Background

Comparative aging studies, particularly those that include species of exceptional resistance to aging processes, can potentially illuminate novel senescence-retarding mechanisms. In recent years, protein homeostasis (proteostasis) has been implicated in fundamental aging processes. Here we further evaluate the relationship between proteostasis and longevity in a selection of bivalve mollusks and mammals with maximum longevities ranging from 3 to 507 years.

Methods & Results

We experimentally examined proteostasis using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a reporter, as it is ubiquitously expressed, highly conserved, and conveniently assayed. The ability to maintain this enzymatic function was tested with increasing concentrations of the chaotropic agent urea, revealing a robust relationship with longevity in bivalves and mice. While our shortest-lived mollusk and mouse lost all activity by 2.5 and 3.5 M urea respectively, the longest-lived mollusk species, Arctica islandica, still preserved 45% of its basal function even at 6 M urea. To confirm that GAPDH proteostasis has a broad association with longevity, we also investigated a selection of primate species ranging in maximum longevity from 22 to 122 years. They outperformed the mouse at all concentrations, but among the primates results were variable at low urea doses. Still, at 6 M urea baboon and human samples retained 10% of their activity while both mouse and marmoset samples had no activity.

Mechanism of Exceptional Stress Resistance

To explore possible mechanisms of the exceptional stress resistance of A. islandica GAPDH we enzymatically removed post-translational glycosylation, but observed no decrease in stability. We also removed molecules smaller than 30 kDa, which includes most small heat shock proteins, but again did not compromise the exceptional stress resistance of Arctica GAPDH.

Conclusion

While the mechanism underlying A. islandica’s exceptional stress resistance remains elusive, this research identifies an experimental system that may reveal hitherto unknown mechanisms of protein homeostasis.     

Restoration of a deciduous woodland in Western Norway formerly used for fodder production: effects on tree canopy and field layer

The rich deciduous woodland at Loi, Luster, Inner Sogn, 61° 20 N., was traditionally used for fodder production from both tree and field layer. After more than nearly 40 years of disuse and secondary forest succession, experimental efforts were made to restore the traditional agricultural meadow woodland. Following a detailed preliminary registration of the vegetation the following measures were taken: