Phosphatidylinositol 3-Kinases

Publication Title: 
Nature

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages.

Author(s): 
Herndon, Laura A.
Schmeissner, Peter J.
Dudaronek, Justyna M.
Brown, Paula A.
Listner, Kristin M.
Sakano, Yuko
Paupard, Marie C.
Hall, David H.
Driscoll, Monica
Publication Title: 
Biochimica Et Biophysica Acta

Studies in a variety of model organisms indicate that nutrient signaling is tightly coupled to longevity. In nutrient replete conditions, organisms develop, grow, and age quickly. When nutrients become sparse as with dietary restriction, growth and development decline, stress response pathways become induced and organisms live longer. Considerable effort has been devoted to understanding the molecular events mediating lifespan extension by dietary restriction.

Author(s): 
Stanfel, Monique N.
Shamieh, Lara S.
Kaeberlein, Matt
Kennedy, Brian K.
Publication Title: 
Current Opinion in Cell Biology

The mammalian ortholog of yeast Atg6/Vps30, Beclin 1, is an essential autophagy protein that has been linked to diverse biological processes, including immunity, development, tumor suppression, lifespan extension, and protection against certain cardiac and neurodegenerative diseases.

Author(s): 
He, Congcong
Levine, Beth
Publication Title: 
Molecular Immunology

Neutrophils are major cells participants in innate host responses. They are short-lived leukocytes, although microbial products activate intracellular signaling cascades that prolong their survival by inhibiting constitutive apoptosis. To gain insight into the phylogeny of this important cell type, we examined the ability of toll-like receptor agonists to extend the lifespan of gilthead seabream (Sparus aurata L.) acidophilic granulocytes, which are the functional equivalent of mammalian neutrophils.

Author(s): 
Sepulcre, MarÌa P.
LÛpez-MuÒoz, Azucena
Angosto, Diego
GarcÌa-Alcazar, Alicia
Meseguer, JosÈ
Mulero, Victoriano
Publication Title: 
PLoS genetics

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking.

Author(s): 
Kruegel, Undine
Robison, Brett
Dange, Thomas
Kahlert, G¸nther
Delaney, Joe R.
Kotireddy, Soumya
Tsuchiya, Mitsuhiro
Tsuchiyama, Scott
Murakami, Christopher J.
Schleit, Jennifer
Sutphin, George
Carr, Daniel
Tar, Krisztina
Dittmar, Gunnar
Kaeberlein, Matt
Kennedy, Brian K.
Schmidt, Marion
Publication Title: 
Oncology Reports

SIRT1 is the human orthologue of SIR2, a conserved NAD-dependent protein deacetylase that regulates longevity in yeast and in Caenorhabditis elegans. Overexpression of SIRT1 in cancer tissue, compared with normal tissue, has been demonstrated, suggesting that SIRT1 may act as a tumor promoter. The function of SIRT1 in liver cancer has not been elucidated. In the present study, SIRT1 re-expression or knockdown was induced in hepatoma cell lines and liver normal cell lines.

Author(s): 
Wang, Hanning
Liu, Hao
Chen, Kaiyun
Xiao, Jinfeng
He, Ke
Zhang, Jinqian
Xiang, Guoan
Publication Title: 
Bioscience, Biotechnology, and Biochemistry

The chronological lifespan (CLS) of budding yeast is a model for the aging of post-mitotic cells in higher eukaryotes. We report here the development of a new method to assess yeast CLS. The new assay is simple, convenient and labor-saving. We applied this new method to screen natural compounds isolated from mushrooms and discovered beauveriolide I as a potent anti-aging agent.

Author(s): 
Nakaya, Shigeru
Mizuno, Saki
Ishigami, Hiroki
Yamakawa, Yasuhiro
Kawagishi, Hirokazu
Ushimaru, Takashi
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Tumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways.

Author(s): 
Min, Siping
Liang, Xue
Zhang, Miaomiao
Zhang, Yuan
Mei, Shiyue
Liu, Jinzhe
Liu, Jingyi
Su, Xiaomin
Cao, Shuisong
Zhong, Xueqing
Li, Yueming
Sun, Jiatan
Liu, Qiaofei
Jiang, Xingran
Che, Yongzhe
Yang, Rongcun
Publication Title: 
Biochemical and Biophysical Research Communications

Cellular senescence is a tumor suppression mechanism. We previously reported that CKII downregulation induces senescence in human lung fibroblast IMR-90 and colon cancer HCT116 cells. In this study, potential longevity drugs, including rapamycin, vitamin C, and vitamin E, blocked CKII downregulation-mediated senescence through reduction of reactive oxygen species (ROS) production in HCT116 cells.

Author(s): 
Park, Ji Hye
Kim, Jin Joo
Bae, Young-Seuk
Publication Title: 
Blood Cells, Molecules & Diseases

The ability of hematopoietic stem cells (HSCs) to self-renew and differentiate into progenitors is essential for homeostasis of the hematopoietic system. The longevity of HSCs makes them vulnerable to accumulating DNA damage, which may be leukemogenic or result in senescence and cell death. Additionally, the ability of HSCs to self-renew and differentiate allows DNA damage to spread throughout the hematologic system, leaving the organism vulnerable to disease.

Author(s): 
Weiss, Cary N.
Ito, Keisuke

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