AMP-Activated Protein Kinases

Publication Title: 
Cell Cycle (Georgetown, Tex.)

Although it has been known since 1917 that calorie restriction (CR) decelerates aging, the topic remains highly controversial. What might be the reason? Here I discuss that the anti-aging effect of CR rules out accumulation of DNA damage and failure of maintenance as a cause of aging. Instead, it suggests that aging is driven in part by the nutrient-sensing TOR (target of rapamycin) network. CR deactivates the TOR pathway, thus slowing aging and delaying diseases of aging.

Author(s): 
Blagosklonny, Mikhail V.
Publication Title: 
Aging

Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies.

Author(s): 
Morselli, Eugenia
Galluzzi, Lorenzo
Kepp, Oliver
Criollo, Alfredo
Maiuri, Maria Chiara
Tavernarakis, Nektarios
Madeo, Frank
Kroemer, Guido
Publication Title: 
FEBS letters

Ageing in mammals remains an unsolved mystery. Anti-ageing is a recurring topic in the history of scientific research. Lifespan extension evoked by Sir2 protein in lower organisms has attracted a large amount of interests in the last decade. This review summarizes recent evidence supporting the role of a Sir2 mammalian homologue, SIRT1 (Silent information regulator T1), in regulating ageing and cellular senescence. The various signaling networks responsible for the anti-ageing and anti-senescence activity of SIRT1 have been discussed.

Author(s): 
Wang, Yu
Liang, Yan
Vanhoutte, Paul M.
Publication Title: 
Nature

Activating AMPK or inactivating calcineurin slows ageing in Caenorhabditis elegans and both have been implicated as therapeutic targets for age-related pathology in mammals. However, the direct targets that mediate their effects on longevity remain unclear. In mammals, CREB-regulated transcriptional coactivators (CRTCs) are a family of cofactors involved in diverse physiological processes including energy homeostasis, cancer and endoplasmic reticulum stress.

Author(s): 
Mair, William
Morantte, Ianessa
Rodrigues, Ana P. C.
Manning, Gerard
Montminy, Marc
Shaw, Reuben J.
Dillin, Andrew
Publication Title: 
Experimental Gerontology

Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C.

Author(s): 
Schiavi, Alfonso
Torgovnick, Alessandro
Kell, Alison
Megalou, Evgenia
Castelein, Natascha
Guccini, Ilaria
Marzocchella, Laura
Gelino, Sara
Hansen, Malene
Malisan, Florence
CondÚ, Ivano
Bei, Roberto
Rea, Shane L.
Braeckman, Bart P.
Tavernarakis, Nektarios
Testi, Roberto
Ventura, Natascia
Publication Title: 
Experimental Gerontology

Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C.

Author(s): 
Schiavi, Alfonso
Torgovnick, Alessandro
Kell, Alison
Megalou, Evgenia
Castelein, Natascha
Guccini, Ilaria
Marzocchella, Laura
Gelino, Sara
Hansen, Malene
Malisan, Florence
CondÚ, Ivano
Bei, Roberto
Rea, Shane L.
Braeckman, Bart P.
Tavernarakis, Nektarios
Testi, Roberto
Ventura, Natascia
Publication Title: 
Journal of Cellular Physiology

Oxidative stress results from damage to tissues caused by free radicals and is increased by exercise. Peroxiredoxins (PRXs) maintain the cellular reducing environment by scavenging intracellular hydrogen peroxide. It has been recently noted that physical exercise has a positive effect on the PRX system, exerting a protective effect against oxidative stress-induced damage. However, other compounds, such as sestrins (SESNs), a stress-inducible protein family with antioxidant properties, should also be considered in the function of PRXs.

Author(s): 
Sanchis-Gomar, Fabian
Publication Title: 
Current Aging Science

Resveratrol, a polyphenol found in several vegetal sources, has been shown to possess lifespan-promoting properties in yeast and metazoans, including small mammals. While in yeast and low metazoans resveratrol acts mainly by activating the histone deacetylase Sir2, in mammals it appears to target - besides the Sir2 homolog SIRT1 - several crucial pathways for the control of metabolism, including the AMPK and the insulin-IGF1 receptors axis.

Author(s): 
Frˆjdˆ, Sara
Durand, Christine
Pirola, Luciano
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Although it has been known since 1917 that calorie restriction (CR) decelerates aging, the topic remains highly controversial. What might be the reason? Here I discuss that the anti-aging effect of CR rules out accumulation of DNA damage and failure of maintenance as a cause of aging. Instead, it suggests that aging is driven in part by the nutrient-sensing TOR (target of rapamycin) network. CR deactivates the TOR pathway, thus slowing aging and delaying diseases of aging.

Author(s): 
Blagosklonny, Mikhail V.
Publication Title: 
Current Aging Science

The discovery of novel uncoupling proteins (UCP2 and UCP3) over 10 years ago heralded a new era of research in mitochondrial uncoupling in a diverse range of tissues. Despite the research vigor, debate stills surrounds the exact function of these uncoupling proteins. For example, the level of uncoupling, the mechanism and mode of action are all under-appreciated at this point in time. Our recent work has used genetic mouse models to focus on the physiological relevance of UCP2. We have used these mouse models to better appreciate the role UCP2 in human health and disease.

Author(s): 
Andrews, Zane B.

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