Dwarfism

Publication Title: 
PLoS genetics

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice.

Author(s): 
Schumacher, Bjˆrn
van der Pluijm, Ingrid
Moorhouse, Michael J.
Kosteas, Theodore
Robinson, Andria Rasile
Suh, Yousin
Breit, Timo M.
van Steeg, Harry
Niedernhofer, Laura J.
van Ijcken, Wilfred
Bartke, Andrzej
Spindler, Stephen R.
Hoeijmakers, Jan H. J.
van der Horst, Gijsbertus T. J.
Garinis, George A.
Publication Title: 
Gerontology

A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity.

Author(s): 
Bartke, Andrzej
Publication Title: 
PloS One

Ames dwarf (Prop1 (df/df) ) mice are remarkably long-lived and exhibit many characteristics of delayed aging and extended healthspan. Caloric restriction (CR) has similar effects on healthspan and lifespan, and causes an extension of longevity in Ames dwarf mice. Our study objective was to determine whether Ames dwarfism or CR influence neuromusculoskeletal function in middle-aged (82 ± 12 weeks old) or old (128 ± 14 w.o.) mice.

Author(s): 
Arum, Oge
Rasche, Zachary Andrew
Rickman, Dustin John
Bartke, Andrzej
Publication Title: 
Science (New York, N.Y.)

Restriction of the number of calories consumed extends longevity in many organisms. In rodents, caloric restriction decreases the levels of plasma glucose and insulin-like growth factor I (IGF-1) and postpones or attenuates cancer, immunosenescence, and inflammation without irreversible side effects. In organisms ranging from yeast to mice, mutations in glucose or IGF-I-like signaling pathways extend life-span but also cause glycogen or fat accumulation and dwarfism.

Author(s): 
Longo, Valter D.
Finch, Caleb E.
Publication Title: 
Science of aging knowledge environment: SAGE KE
Author(s): 
Landhuis, Esther
Publication Title: 
Best Practice & Research. Clinical Endocrinology & Metabolism

Research with invertebrates over the past 10 years has suggested that alterations in insulin and/or insulin-like growth factor I (IGF-I) signalling result in increased lifespan and retard ageing. In this chapter, we describe the current research in mammalian systems with respect to the role of insulin or IGF-I in ageing. Using rodent models of caloric restriction and genetic mouse models, e.g.

Author(s): 
Richardson, Arlan
Liu, Feng
Adamo, Martin L.
Van Remmen, Holly
Nelson, James F.
Publication Title: 
Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et MÈtabolisme

We examined the effects of diets based on a low isoflavone or a high isoflavone soy protein isolates in normal, growth-hormone receptor knockout and Ames dwarf, and Prop 1 (df) mice that are hypoinsulinemic, insulin-sensitive, and exceptionally long-lived, as well as in growth hormone transgenic mice that are hyperinsulinemic, insulin-resistant, dyslipidemic, and short-lived. Soybean diets tended to normalize plasma cholesterol levels in dwarf and transgenic mice, while low isoflavone diet reduced plasma triglycerides in most of the examined genotypes.

Author(s): 
Bartke, A.
Peluso, M. R.
Moretz, N.
Wright, C.
Bonkowski, M.
Winters, T. A.
Shanahan, M. F.
Kopchick, J. J.
Banz, W. J.
Publication Title: 
Current Topics in Developmental Biology

Ames dwarf mice and Snell dwarf mice lack growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH), live much longer than their normal siblings, and exhibit many symptoms of delayed aging. "Laron dwarf mice," produced by targeted disruption of the GH receptor/GH-binding protein gene (GHR-KO mice), are GH resistant and also live much longer than normal animals from the same line. Isolated GH deficiency in "little" mice is similarly associated with increased life span, provided that obesity is prevented by reducing fat content in the diet.

Author(s): 
Bartke, Andrzej
Brown-Borg, Holly
Publication Title: 
PLoS genetics

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice.

Author(s): 
Schumacher, Bjˆrn
van der Pluijm, Ingrid
Moorhouse, Michael J.
Kosteas, Theodore
Robinson, Andria Rasile
Suh, Yousin
Breit, Timo M.
van Steeg, Harry
Niedernhofer, Laura J.
van Ijcken, Wilfred
Bartke, Andrzej
Spindler, Stephen R.
Hoeijmakers, Jan H. J.
van der Horst, Gijsbertus T. J.
Garinis, George A.
Publication Title: 
Gerontology

What aging process is delayed by calorie restriction (CR) and mutations that produce long-lived dwarf mice? From 1935 until 1996, CR was the only option for increasing the maximum lifespan of laboratory rodents. In 1996, the mutation producing the Ames dwarf mouse (Prop-1(-/-)) was reported to increase lifespan. Since 1996, other gene mutations that cause dwarfism or lower body weight have been reported to increase the lifespan of mice. The recent discovery of long-lived mutant dwarf mice provides an opportunity to investigate common features between CR and dwarf models.

Author(s): 
McKee Alderman, J.
DePetrillo, Michael A.
Gluesenkamp, Angela M.
Hartley, Antonia C.
Verhoff, S. Veronica
Zavodni, Katherine L.
Combs, Terry P.

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