Specific protein homeostatic functions of small heat‐shock proteins increase lifespan

Abstract

SummaryDuring aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat‐shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress‐denatured substrates and/or to prevent aggregation of disease‐associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70‐dependent refolding of stress‐denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70‐independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo.

Effect of short-term high-temperature exposure on the life history parameters of Ophraella communa

“…Mild temperature hardening in nature can increase insects’ thermotolerance 51 ; thus, the time at which insect samples are collected from the field also influences adult longevity under heat stress. Some previous studies also reported that heat stress increased the longevity of some Drosophila species 62 , such as D . melanogaster males (exposure of adults to 34 °C for 3 h) 63 , parasitoids, such as females of the wasp A .…”

MiR-34 inhibits polycomb repressive complex 2 to modulate chaperone expression and promote healthy brain aging

“…7a , Supplementary Figure 5, Supplementary Table 2 ). This overlap is particularly noteworthy for protein aggregation processes, as this family of small chaperones has been reported to mitigate polyglutamine toxicity and extend lifespan 17 , 18 , 36 . Five alpha-crystallin/sHSP genes were upregulated in E(z) mutants: Hsp23, Hsp26, Hsp27, CG13133 , and CG7409 .…”

Ovary Proteome Analysis Reveals RH36 Regulates Reproduction via Vitellin Uptake Mediated by HSP70 Protein in Hard Ticks

“…We speculated that nutrition deficiency accelerated HSP70-mediated cell damage in ticks (Figure 10). The expression of HSP with antioxidant activity extends lifespan via regulating the downstream protein autophagy-related gene 7 (Morrow et al, 2004;Liao et al, 2008;Chen et al, 2012;Sarup et al, 2014;Vos et al, 2016), while HSP depletion reduces the number of viviparous offspring and simultaneously increases the number of premature nymphs, suggesting an unexpected role in aphid embryogenesis and eclosion (Will et al, 2017). Therefore, it is suggested that RH36 gene regulates vitellogenin uptake via HSP70 protein and extends lifespan of ovary to improve oviposition rate.…”