Animals, Genetically Modified

Publication Title: 
Free Radical Biology & Medicine

Mutations in human CuZn superoxide dismutase (SOD) have been associated with familial amyotrophic lateral sclerosis (FALS). Although leading to many experimental advances, this finding has not yet led to a clear understanding of the biochemical mechanism by which mutations in SOD promote the degeneration of motorneurons that causes this incurable paralytic disease.

Elia, A. J.
Parkes, T. L.
Kirby, K.
St George-Hyslop, P.
Boulianne, G. L.
Phillips, J. P.
Hilliker, A. J.
Publication Title: 
Aging Cell

Molecular advances of the past decade have led to the discovery of a myriad of 'aging genes' (methuselah, Indy, InR, Chico, superoxide dismutase) that extend Drosophila lifespan by up to 85%. Despite this life extension, these mutants are no longer lived than at least some recently wild-caught strains. Typically, long-lived mutants are identified in relatively short-lived genetic backgrounds, and their effects are rarely tested in genetic backgrounds other than the one in which they were isolated or derived.

Spencer, Christine C.
Howell, Christine E.
Wright, Amber R.
Promislow, Daniel E. L.
Publication Title: 
Aging Cell

Major advances in aging research have been made by studying the effect of genetic modifications on the lifespan of organisms, such as yeast, invertebrates (worms and flies) and mice. Data from yeast and invertebrates have been the most plentiful because of the ease in which genetic manipulations can be made and the rapidity by which lifespan experiments can be performed. With the ultimate focus on advancing human health, testing genetic interventions in mammals is crucial, and the mouse has proven to be the mammal most amenable to this task.

Ladiges, Warren
Van Remmen, Holly
Strong, Randy
Ikeno, Yuji
Treuting, Piper
Rabinovitch, Peter
Richardson, Arlan
Publication Title: 
Rejuvenation Research

A botanical extract (Regrapex-R) prepared from whole grape (Vitis vinifera) and Polygonum cuspidatum, which contains polyphenols, including flavans, anthocyanins, emodin, and resveratrol, exhibited dose-dependent scavenging effects on reactive oxygen species (ROS). The extract inhibited increases of ROS and protein carbonyl in isolated rat liver mitochondria following exposure to 2,2'-azobis (2-amidino propane) dihydrocholoride (AAPH), a potent lipid oxidant generator.

Long, Jiangang
Gao, Hongxiang
Sun, Lijuan
Liu, Jiankang
Zhao-Wilson, Xi
Publication Title: 
Experimental Gerontology

As in the case of aging, many degenerative disorders also result from progressive mitochondrial deterioration and cellular damage accumulation. Therefore, preventing damage accumulation may delay aging and help to prevent degenerative disorders, especially those associated with mitochondrial dysfunction. In the nematode Caenorhabditis elegans a mild mitochondrial dysfunction prolongs the lifespan.

Torgovnick, Alessandro
Schiavi, Alfonso
Testi, Roberto
Ventura, Natascia
Publication Title: 
International Journal of Nanomedicine

Platinum nanoparticle (Pt-np) species are superoxide dismutase/catalase mimetics and also have an activity similar to that of mitochondrial electron transport complex I. To examine if this complex I-like activity functions in vivo, we studied the effects of Pt-nps on the lifespan of a mitochondrial complex I-deficient Caenorhabditis elegans mutant, nuo-1 (LB25) compared with wild-type N2. We synthesized a fusion protein of a cell-penetrating peptide, human immunodeficiency virus-1 TAT (48-60), C-terminally linked to a peptide with a high affinity to platinum (GRKKRRQRRRPPQ-DRTSTWR).

Sakaue, Yuri
Kim, Juewon
Miyamoto, Yusei
Publication Title: 
PLoS genetics

We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally, we extended lifespan by increasing the activity of four endogenous worm aging pathways.

Sagi, Dror
Kim, Stuart K.
Publication Title: 

Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures.

Xiao, Rui
Zhang, Bi
Dong, Yongming
Gong, Jianke
Xu, Tao
Liu, Jianfeng
Xu, X. Z. Shawn
Publication Title: 
Neurobiology of Disease

An increasing body of evidence indicates a role for oligomers of the amyloid-? peptide (A?) in the neurotoxicity of this peptide and the pathology of Alzheimer's disease (AD). Several neurotoxic oligomeric forms of A? have been noted ranging from the larger Amyloid ?-Derived Diffusible Ligands (ADDLs) to smaller trimers and dimers of A?. More recently a dodecameric form of A? with a 56 kDa molecular weight, denoted A?*56, was shown to cause memory impairment in AD model mice.

Scherzer-Attali, R.
Farfara, D.
Cooper, I.
Levin, A.
Ben-Romano, T.
Trudler, D.
Vientrov, M.
Shaltiel-Karyo, R.
Shalev, D. E.
Segev-Amzaleg, N.
Gazit, E.
Segal, D.
Frenkel, D.
Publication Title: 
Biochemical and Biophysical Research Communications

Clusterin is a disulfide-linked heterodimeric glycoprotein that has been implicated in a variety of biological processes. Its expression has been shown to be elevated during cellular senescence and normal aging, but it is uncertain whether clusterin protects against aging or whether its expression is a consequence of aging. To investigate the functions of clusterin during organismal aging, we established transgenic Drosophila alleles to induce the expression of the secretory form of human clusterin (hClu(S)) using the Gal4/UAS system.

Lee, Young-Nam
Shim, Young-Jun
Kang, Byeong-Ho
Park, Joong-Jean
Min, Bon-Hong


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