Enhanced protein repair and recycling are not correlated with longevity in 15 vertebrate endotherm species

Abstract

Previous studies have shown that longevity is associated with enhanced cellular stress resistance. This observation supports the disposable soma theory of aging, which suggests that the investment made in cellular maintenance will be proportional to selective pressures to extend lifespan. Maintenance of protein homeostasis is a critical component of cellular maintenance and stress resistance. To test the hypothesis that enhanced protein repair and recycling activities underlie longevity, we measured the activities of the 20S/26S proteasome and two protein repair enzymes in liver, heart and brain tissues of 15 different mammalian and avian species with maximum lifespans (MLSP) ranging from 3 to 30 years. The data set included Snell dwarf mice, in which lifespan is increased by ∼50% compared to their normal littermates. None of these activities in any of the three tissues correlated positively with MLSP. In liver, 20S/26S proteasome and thioredoxin reductase (TrxR) activities correlated negatively with body mass. In brain tissue, TrxR was also negatively correlated with body mass. Glutaredoxin (Grx) activity in brain was negatively correlated with MLSP and this correlation remained after residual analysis to remove the effects of body mass, but was lost when the data were analysed using Felsenstein's independent contrasts. Snell dwarf mice had marginally lower 20S proteasome, TrxR and Grx activities than normal controls in brain, but not heart tissue. Thus, increased longevity is not associated with increased protein repair or proteasomal degradation capacities in vertebrate endotherms.

What patients say about living with psychogenic nonepileptic seizures: A systematic synthesis of qualitative studies

“…Some of the main themes of this study seem to be largely confirmatory and applicable to most chronic conditions where patients value well-resourced services [8,12,16,17], good social support [1,5,16,17,18] and medical insurance that covers the diagnostic process [11].…”

“…PNES is a complex and controversial disorder that remains poorly understood and managed in the clinical setting [2]. Nevertheless, PNES is a common neuropsychiatric condition which is often misdiagnosed as ES due to the similarities in presentation, frequently resulting in prolonged treatment with anti-epileptic drugs (AED), and avoided by many healthcare providers [1,3,4,5]. Associated stigma and loss of quality of life are compound consequences of misdiagnosis [6].…”

“…Studies indicate that the average period between seizure manifestation and correct 2 diagnosis of PNES is about seven years [10]. During the diagnostic process patients are often confronted with extensive and expensive testing [11] as well as a lack of understanding of this condition from healthcare providers [1,5,8,12]. Early diagnosis of PNES is therefore not only important in reducing the significant costs to the patient and healthcare systems, or in decreasing the major side-effects due to incorrect treatment [1].…”

Activities of DNA base excision repair enzymes in liver and brain correlate with body mass, but not lifespan

“…This suggests that the rate at which macromolecular oxidative damage (to both proteins and DNA) occurs probably decreases with increasing body mass, and therefore the rates of recycling/repair required to maintain cellular homeostasis and viability are concomitantly reduced. An important caveat, however, is that both protein (Salway et al 2011) and DNA homeostasis activities were measured under non-stressed conditions, so we cannot detect any differences in the inducibility of these activities that might exist between species and be related to MLSP. Another concept critical to the interpretation of the data in this study is that relationships between BER (or other DNA repair activities) and lifespan may be highly cell-type specific.…”

“…Salway et al (2011) showed that the 20S/26S proteasome, as well as the activities of enzymes capable of maintaining the redox state of proteins, generally correlate negatively with species body mass but show no relationship with MLSP. This suggests that the rate at which macromolecular oxidative damage (to both proteins and DNA) occurs probably decreases with increasing body mass, and therefore the rates of recycling/repair required to maintain cellular homeostasis and viability are concomitantly reduced.…”