Protein Folding

Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

The burden of protein misfolding is believed to contribute to aging. However, the links between adaptations to conditions associated with protein misfolding and resistance to the time-dependent attrition of cellular function remain poorly understood. We report that worms lacking aip-1, a homologue of mammalian AIRAP (arsenic-inducible proteasomal 19S regulatory particle-associated protein), are not only impaired in their ability to resist exposure to arsenite but also exhibit shortened lifespan and hypersensitivity to misfolding-prone proteins under normal laboratory conditions.

Author(s): 
Yun, Chi
Stanhill, Ariel
Yang, Yun
Zhang, Yuhong
Haynes, Cole M.
Xu, Chong-Feng
Neubert, Thomas A.
Mor, Adam
Philips, Mark R.
Ron, David
Publication Title: 
Aging Cell

Sir2 ? Sirt1 and its orthologues are known lifespan extension factors in several aging models from yeast to invertebrates. Sirt1 activation is also known to be beneficial and protective in both invertebrate and mammalian models of neurodegenerative disease. Sirt1ís lifespan extension effect, as well as the beneficial outcome of its activation in models of aging-associated diseases, is often attributed to its ability to instill a gene expression profile that is pro-survival and antiaging.

Author(s): 
Gan, Bin Qi
Tang, Bor Luen
Publication Title: 
PLoS genetics

Cells respond to accumulation of misfolded proteins in the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR) signaling pathway. The UPR restores ER homeostasis by degrading misfolded proteins, inhibiting translation, and increasing expression of chaperones that enhance ER protein folding capacity. Although ER stress and protein aggregation have been implicated in aging, the role of UPR signaling in regulating lifespan remains unknown. Here we show that deletion of several UPR target genes significantly increases replicative lifespan in yeast.

Author(s): 
Labunskyy, Vyacheslav M.
Gerashchenko, Maxim V.
Delaney, Joe R.
Kaya, Alaattin
Kennedy, Brian K.
Kaeberlein, Matt
Gladyshev, Vadim N.
Publication Title: 
Rejuvenation Research

Bile acids are detergent molecules derived from cholesterol in the liver that are important for the metabolism and absorption of lipids in the intestine. Bile acids are also steroid hormones activating specific nuclear receptors and G protein-coupled receptors. Conjugated bile acids are cytoprotective and anticarcinogenic. Bile acid synthesis and bile flow decreases markedly during aging.

Author(s): 
Kr¯ll, Jens
Publication Title: 
Neuromolecular Medicine

A common cause of amyotrophic lateral sclerosis is mutations in superoxide dismutase-1, which provoke the disease by an unknown mechanism. We have previously found that soluble hydrophobic misfolded mutant human superoxide dismutase-1 species are enriched in the vulnerable spinal cords of transgenic model mice. The levels were broadly inversely correlated with life spans, suggesting involvement in the pathogenesis.

Author(s): 
Zetterstrˆm, Per
Graffmo, Karin S.
Andersen, Peter M.
Br‰nnstrˆm, Thomas
Marklund, Stefan L.
Publication Title: 
PLoS genetics

Cells respond to accumulation of misfolded proteins in the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR) signaling pathway. The UPR restores ER homeostasis by degrading misfolded proteins, inhibiting translation, and increasing expression of chaperones that enhance ER protein folding capacity. Although ER stress and protein aggregation have been implicated in aging, the role of UPR signaling in regulating lifespan remains unknown. Here we show that deletion of several UPR target genes significantly increases replicative lifespan in yeast.

Author(s): 
Labunskyy, Vyacheslav M.
Gerashchenko, Maxim V.
Delaney, Joe R.
Kaya, Alaattin
Kennedy, Brian K.
Kaeberlein, Matt
Gladyshev, Vadim N.
Publication Title: 
Biochimica Et Biophysica Acta

Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of their extreme toxicity but also paradoxically for their therapeutic applications. All the known serotypes (A-G) have varying degrees of longevity and potency inside the neuronal cell. Differential chemical modifications such as phosphorylation and ubiquitination have been suggested as possible mechanisms for their longevity, but the molecular basis of the longevity remains unclear.

Author(s): 
Kumar, Raj
Kukreja, Roshan V.
Cai, Shuowei
Singh, Bal R.
Publication Title: 
Nature

The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage. Damage that occurs within stressed HSCs must be tightly controlled to prevent either loss of function or the clonal persistence of oncogenic mutations that increase the risk of leukaemogenesis.

Author(s): 
van Galen, Peter
Kreso, Antonija
Mbong, Nathan
Kent, David G.
Fitzmaurice, Timothy
Chambers, Joseph E.
Xie, Stephanie
Laurenti, Elisa
Hermans, Karin
Eppert, Kolja
Marciniak, Stefan J.
Goodall, Jane C.
Green, Anthony R.
Wouters, Bradly G.
Wienholds, Erno
Dick, John E.
Publication Title: 
Cell Stress & Chaperones

Chaperone function plays a key role in repairing proteotoxic damage, in the maintenance of cell architecture, and in cell survival. Here, we summarize our current knowledge about changes in chaperone expression and function in the aging process, as well as their involvement in longevity and cellular senescence.

Author(s): 
Soti, Csaba
Csermely, PÈter
Publication Title: 
Aging Cell

Nutrient availability influences an organism's life history with profound effects on metabolism and lifespan. The association between a healthy lifespan and metabolism is incompletely understood, but a central factor is glucose metabolism. Although glucose is an important cellular energy source, glucose restriction is associated with extended lifespan in simple animals and a reduced incidence of age-dependent pathologies in humans. We report here that glucose enrichment delays mutant polyglutamine, TDP-43, FUS, and amyloid-?

Author(s): 
Tauffenberger, Arnaud
Vaccaro, Alexandra
Aulas, Anais
Vande Velde, Christine
Parker, J. Alex

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