SIRT1 but not its increased expression is essential for lifespan extension in caloric-restricted mice

نویسندگان

  • Evi M Mercken
  • Jia Hu
  • Susan Krzysik-Walker
  • Min Wei
  • Ying Li
  • Michael W McBurney
  • Rafael de Cabo
  • Valter D Longo
چکیده

The SIRT1 deacetylase is one of the best-studied putative mediators of some of the anti-aging effects of calorie restriction (CR), but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild-type mice on an ad libitum diet. Here, we report that median lifespan extension in CR heterozygote SIRT1(+/-) mice was identical (51%) to that observed in wild-type mice, but SIRT1(+/-) mice displayed a higher frequency of certain pathologies. Although larger studies in additional genetic backgrounds are needed, these results provide strong initial evidence for the requirement of SIRT1 for the lifespan extension effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Activation-Induced Apoptosis in T cells: Effect of Age and Caloric Restriction

We have previously shown that the proliferative response of T cells to antigenic or mitogenic stimulus decreased with age and that caloric resection (CR) attenuated the age-related decline in proliferation and IL-2 expression. Because activation-induced apoptosis is known to regulate cell proliferation and eliminate the high number of activated cells during an immune response, it was of interes...

متن کامل

SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice

The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have...

متن کامل

p16INK4a Suppression by Glucose Restriction Contributes to Human Cellular Lifespan Extension through SIRT1-Mediated Epigenetic and Genetic Mechanisms

Although caloric restriction (CR) has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellu...

متن کامل

Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro

The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vi...

متن کامل

Sir-viving cardiac stress: cardioprotection mediated by a longevity gene.

Over the last decade, a number of genetic modifiers of yeast and animal lifespan have been discovered and studied in some detail. Many of these genes lie on or impinge on the evolutionarily conserved insulin signaling pathway.1 In fact, one of the first genes discovered that was linked to lifespan regulation in Caenorhabditis elegans was DAF2, the product of which is highly related to mammalian...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 13  شماره 

صفحات  -

تاریخ انتشار 2014