Publication Title: 

The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis.

Kim, Eun Bae
Fang, Xiaodong
Fushan, Alexey A.
Huang, Zhiyong
Lobanov, Alexei V.
Han, Lijuan
Marino, Stefano M.
Sun, Xiaoqing
Turanov, Anton A.
Yang, Pengcheng
Yim, Sun Hee
Zhao, Xiang
Kasaikina, Marina V.
Stoletzki, Nina
Peng, Chunfang
Polak, Paz
Xiong, Zhiqiang
Kiezun, Adam
Zhu, Yabing
Chen, Yuanxin
Kryukov, Gregory V.
Zhang, Qiang
Peshkin, Leonid
Yang, Lan
Bronson, Roderick T.
Buffenstein, Rochelle
Wang, Bo
Han, Changlei
Li, Qiye
Chen, Li
Zhao, Wei
Sunyaev, Shamil R.
Park, Thomas J.
Zhang, Guojie
Wang, Jun
Gladyshev, Vadim N.
Publication Title: 
Mechanisms of Ageing and Development

Interventions which inhibit TOR activity (including rapamycin and caloric restriction) lead to downstream gene expression changes and increased lifespan in laboratory models. However, the role of mTOR signaling in human aging is unclear. We tested the expression of mTOR-related transcripts in two independent study cohorts; the InCHIANTI population study of aging and the San Antonio Family Heart Study (SAFHS). Expression of 27/56 (InCHIANTI) and 19/44 (SAFHS) genes were associated with age after correction for multiple testing. 8 genes were robustly associated with age in both cohorts.

Harries, Lorna W.
Fellows, Alexander D.
Pilling, Luke C.
Hernandez, Dena
Singleton, Andrew
Bandinelli, Stefania
Guralnik, Jack
Powell, Jonathan
Ferrucci, Luigi
Melzer, David
Publication Title: 
The Journal of Investigative Dermatology

Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply 3'-end sequencing for expression quantification ("3-seq") to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed "skin aging"), and the impact of broadband light (BBL) treatment.

Chang, Anne Lynn S.
Bitter, Patrick H.
Qu, Kun
Lin, Meihong
Rapicavoli, Nicole A.
Chang, Howard Y.
Publication Title: 

Dietary composition has major effects on physiology. Here, we show that developmental rate, reproduction, and lifespan are altered in C.†elegans fed Comamonas DA1877 relative to those fed a standard E.†coli OP50 diet. We identify a set of genes that change in expression in response to this diet and use the promoter of one of these (acdh-1) as a dietary sensor. Remarkably, the effects on transcription and†development occur even when Comamonas DA1877 is diluted with another diet, suggesting that Comamonas DA1877 generates a signal that is sensed by the nematode.

MacNeil, Lesley T.
Watson, Emma
Arda, H. Efsun
Zhu, Lihua Julie
Walhout, Albertha J. M.
Publication Title: 
Aging Cell

Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR induces dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals.

Mercken, Evi M.
Crosby, Seth D.
Lamming, Dudley W.
JeBailey, Lellean
Krzysik-Walker, Susan
Villareal, Dennis T.
Capri, Miriam
Franceschi, Claudio
Zhang, Yongqing
Becker, Kevin
Sabatini, David M.
de Cabo, Rafael
Fontana, Luigi
Publication Title: 
Nature Communications

Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake.

Martin-Montalvo, Alejandro
Mercken, Evi M.
Mitchell, Sarah J.
Palacios, Hector H.
Mote, Patricia L.
Scheibye-Knudsen, Morten
Gomes, Ana P.
Ward, Theresa M.
Minor, Robin K.
Blouin, Marie-José
Schwab, Matthias
Pollak, Michael
Zhang, Yongqing
Yu, Yinbing
Becker, Kevin G.
Bohr, Vilhelm A.
Ingram, Donald K.
Sinclair, David A.
Wolf, Norman S.
Spindler, Stephen R.
Bernier, Michel
de Cabo, Rafael
Publication Title: 

Calorie Restriction (CR) without malnutrition slows aging and increases average and maximal lifespan in simple model organisms and rodents. In rhesus monkeys long-term CR reduces the incidence of type 2 diabetes, cardiovascular disease and cancer, and protects against age-associated sarcopenia and neurodegeneration. However, so far CR significantly increased average lifespan only in the Wisconsin, but not in the NIA monkey study. Differences in diet composition and study design between the 2 on-going trials may explain the discrepancies in survival and disease.

Cava, Edda
Fontana, Luigi
Publication Title: 
Molecular and Cellular Biology

Telomerase canonically maintains telomeres, but recent reports have suggested that the core protein mammalian telomerase reverse transcriptase (TERT) component, together with the chromatin remodeling factor BRG1 and ?-catenin, may also bind to and promote expression of Wnt target genes. However, this proposed noncanonical role of TERT in Wnt signaling has been controversial. Here, we investigated the effects of human TERT (hTERT) on Wnt signaling in human breast cancer lines and HeLa cells.

Listerman, Imke
Gazzaniga, Francesca S.
Blackburn, Elizabeth H.
Publication Title: 
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics

Several studies have evaluated the potential utility of blood-based whole-transcriptome signatures as a source of biomarkers for schizophrenia. This endeavor has been complicated by the fact that individuals with schizophrenia typically differ from appropriate comparison subjects on more than just the presence of the disorder; for example, individuals with schizophrenia typically receive antipsychotic medications, and have been dealing with the sequelae of this chronic illness for years.

Glatt, Stephen J.
Stone, William S.
Nossova, Nadine
Liew, Choong-Chin
Seidman, Larry J.
Tsuang, Ming T.
Publication Title: 

Acquisition and maintenance of cell fate and potential are dependent on the complex interplay of extracellular signaling, gene regulatory networks and epigenetic states. During embryonic development, embryonic stem cells become progressively more restricted along specific lineages, ultimately giving rise to the diversity of cell types in the adult mammalian organism. Recent years have seen major advances in our understanding of the mechanisms that regulate the underlying transcriptional programmes during development.

Bithell, Angela


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