The drug rapamycin has been shown to extend lifespan in labanimals, yet rapamycin has also been linked to impaired glucosetolerance and insulin sensitivity, two hallmarks of diabetes . By teasing apart rapamycin's activity at the cellular level,researchers at Whitehead Institute and the University ofPennsylvania have determined that inhibiting only the proteincluster known as the mechanistic target of rapamycin complex 1(mTORC1) prolongs life in mice without adversely affecting glucosetolerance or insulin sensitivity. With this novel understanding of how rapamycin produces itsanti-aging effects, researchers may be able to develop a drug thatspecifically targets mTORC1, thereby promoting longevity whilepreventing the adverse effects associated with rapamycin. One of the secrets to a longer, healthier life is simply to eatless.
When subjected to calorie restriction (CR), typically definedas a 20-40% reduction in caloric intake with correspondingmaintenance of proper nutrition , animals in labs not only live longer, but also have improvedinsulin sensitivity and glucose tolerance, both of which declineduring aging. Yet, for all of its benefits, CR's restricted diet is a stumblingblock for most Americans. If only we had a drug that could do thesame thing. Well, we do, sort of. The drug rapamycin, which is used forimmunosuppression in organ transplantations, mimics the longevityeffects of CR and may tap into the same cellular pathway as CR.Unlike CR, however, rapamycin actually impairs glucose toleranceand insulin sensitivity, two hallmarks of diabetes.
Clearly,rapamycin is doing something CR is not. To understand better rapamycin's benefits and risks, researchersfrom the lab of Whitehead Institute Member David Sabatini andJoseph Baur, assistant professor of Physiology, at the Universityof Pennsylvania's Perelman School of Medicine, have discoveredprecisely how rapamycin is behaving at the cellular level. Theirintriguing results are published in the journal Science. "We know that despite its adverse effects, rapamycin still prolongslifespan, so there's a potential that we could make it better byjust having lifespan affected and not induce the adverse effects,"says Sabatini, who is a professor of biology at MIT and a HowardHughes Medical Institute (HHMI) investigator. Recycled Shopping Bags
"The data in thispaper suggest that it's possible." Rapamycin, which is also called sirolimus and marketed in theUnited States as Rapamune , is a known inhibitor of the mechanistic target of rapamycincomplex 1 (mTORC1), a protein complex that regulates many cellularprocesses linked to growth and differentiation. mTORC1 is part of acellular signaling pathway, called mTOR, which responds tonutrients and growth factors. Mechanistic target of rapamycincomplex 2 (mTORC2) is also part of the mTOR pathway and regulatesinsulin signaling. Rapamycin has generally been thought to target primarily mTORC1.But work by Dudley Lamming and Lan Ye, co-authors of the Sciencepaper and postdoctoral fellows in the Sabatini and Baur labsrespectively, indicates that in mice, rapamycin also inhibitsmTORC2, thereby reducing insulin sensitivity. To see if rapamycin's positive effects on lifespan effects could beseparated from its negative metabolic effects, Lamming and Ye bredmice whose mTORC1 activity was partially inhibited but whose mTORC2activity remained largely intact. Handmade Felt Bags Manufacturer
The females of this mousepopulation lived longer than control mice while maintaining normalinsulin sensitivity. "This shows that disrupting mTORC1 alone is capable of extendinglifespan, if you can find a way do that," says Lamming. For Baur, the experiments' results indicate that there is apossibility of identifying a better anti-aging drug than rapamycin. "Our work highlights the potential utility of molecules that targetmTORC1 specifically and suggests there is hope that by targetingthis pathway, you could really get something that ameloriatesage-related diseases without causing more problems than it solves,"says Baur. China RPET Bag
"If you're taking an anti-aging drug as a preventivemeasure, you probably don't want to pay the price of diabetes.".
When subjected to calorie restriction (CR), typically definedas a 20-40% reduction in caloric intake with correspondingmaintenance of proper nutrition , animals in labs not only live longer, but also have improvedinsulin sensitivity and glucose tolerance, both of which declineduring aging. Yet, for all of its benefits, CR's restricted diet is a stumblingblock for most Americans. If only we had a drug that could do thesame thing. Well, we do, sort of. The drug rapamycin, which is used forimmunosuppression in organ transplantations, mimics the longevityeffects of CR and may tap into the same cellular pathway as CR.Unlike CR, however, rapamycin actually impairs glucose toleranceand insulin sensitivity, two hallmarks of diabetes.
Clearly,rapamycin is doing something CR is not. To understand better rapamycin's benefits and risks, researchersfrom the lab of Whitehead Institute Member David Sabatini andJoseph Baur, assistant professor of Physiology, at the Universityof Pennsylvania's Perelman School of Medicine, have discoveredprecisely how rapamycin is behaving at the cellular level. Theirintriguing results are published in the journal Science. "We know that despite its adverse effects, rapamycin still prolongslifespan, so there's a potential that we could make it better byjust having lifespan affected and not induce the adverse effects,"says Sabatini, who is a professor of biology at MIT and a HowardHughes Medical Institute (HHMI) investigator. Recycled Shopping Bags
"The data in thispaper suggest that it's possible." Rapamycin, which is also called sirolimus and marketed in theUnited States as Rapamune , is a known inhibitor of the mechanistic target of rapamycincomplex 1 (mTORC1), a protein complex that regulates many cellularprocesses linked to growth and differentiation. mTORC1 is part of acellular signaling pathway, called mTOR, which responds tonutrients and growth factors. Mechanistic target of rapamycincomplex 2 (mTORC2) is also part of the mTOR pathway and regulatesinsulin signaling. Rapamycin has generally been thought to target primarily mTORC1.But work by Dudley Lamming and Lan Ye, co-authors of the Sciencepaper and postdoctoral fellows in the Sabatini and Baur labsrespectively, indicates that in mice, rapamycin also inhibitsmTORC2, thereby reducing insulin sensitivity. To see if rapamycin's positive effects on lifespan effects could beseparated from its negative metabolic effects, Lamming and Ye bredmice whose mTORC1 activity was partially inhibited but whose mTORC2activity remained largely intact. Handmade Felt Bags Manufacturer
The females of this mousepopulation lived longer than control mice while maintaining normalinsulin sensitivity. "This shows that disrupting mTORC1 alone is capable of extendinglifespan, if you can find a way do that," says Lamming. For Baur, the experiments' results indicate that there is apossibility of identifying a better anti-aging drug than rapamycin. "Our work highlights the potential utility of molecules that targetmTORC1 specifically and suggests there is hope that by targetingthis pathway, you could really get something that ameloriatesage-related diseases without causing more problems than it solves,"says Baur. China RPET Bag
"If you're taking an anti-aging drug as a preventivemeasure, you probably don't want to pay the price of diabetes.".