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Literature DB >> 12057928

Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model.

Isao Shimokawa¹, Yoshikazu Higami, Masanori Utsuyama, Tomoshi Tuchiya, Toshimitsu Komatsu, Takuya Chiba, Haruyoshi Yamaza.

Abstract

The longer life span in dwarf mice suggests that a reduction in the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis retards aging and extends the life span in mammals. We tested this hypothesis in a transgenic strain of rats whose GH gene was suppressed by an anti-sense GH transgene. Male rats homozygous for the transgene (tg/tg) had a reduced number of pituitary GH cells, a lower plasma concentration of IGF-1, and a dwarf phenotype. Heterozygous rats (tg/-) had an intermediate phenotype in plasma IGF-1, food intake, and body weight between tg/tg and control (-/-) rats. The life span of tg/tg rats was 5 to 10% shorter than -/- rats. In contrast, the life span of tg/- rats was 7 to 10% longer than -/- rats. Pathological analysis suggested that neoplasms caused earlier death in tg/tg rats; in contrast, tg/- rats had reduced nonneoplastic diseases and a prolonged life span. Immunological analysis revealed a smaller population and lower activity of splenic natural killer cells in tg/tg rats. The results of the present study support the hypothesis, but suggest that there is an optimal level of the GH-IGF-1 axis to maximize survival in mammals.

Entities: Disease Gene Species

Mesh：

Substances：

Year: 2002 PMID： 12057928 PMCID： PMC1850833 DOI： 10.1016/S0002-9440(10)61173-X

Source DB: PubMed Journal: Am J Pathol ISSN： 0002-9440 Impact factor: 4.307

20 in total

1. Immunological restoration and anti-tumor effect by Japanese herbal medicine in aged mice.

Authors: M Utsuyama; H Seidlar; M Kitagawa; K Hirokawa
Journal: Mech Ageing Dev Date: 2001-03 Impact factor: 5.432

Review 2. Prolonged longevity of hypopituitary dwarf mice.

Authors: A Bartke; H Brown-Borg; J Mattison; B Kinney; S Hauck; C Wright
Journal: Exp Gerontol Date: 2001-01 Impact factor: 4.032

3. Differential longevity in mouse stocks selected for early life growth trajectory.

Authors: R A Miller; C Chrisp; W Atchley
Journal: J Gerontol A Biol Sci Med Sci Date: 2000-09 Impact factor: 6.053

4. Glomerular lesions in mice transgenic for growth hormone and insulinlike growth factor-I. I. Relationship between increased glomerular size and mesangial sclerosis.

Authors: T Doi; L J Striker; C C Gibson; L Y Agodoa; R L Brinster; G E Striker
Journal: Am J Pathol Date: 1990-09 Impact factor: 4.307

5. Immunological enhancement with a low dose of cyclophosphamide in aged mice.

Authors: N Ishiyama; M Utsuyama; M Kitagawa; K Hirokawa
Journal: Mech Ageing Dev Date: 1999-11-02 Impact factor: 5.432

Review 6. Definition and functions of natural killer cells.

Authors: E Lotzová
Journal: Nat Immun Date: 1993 Jul-Oct

7. Nutritional influences on aging of Fischer 344 rats: II. Pathology.

Authors: H Maeda; C A Gleiser; E J Masoro; I Murata; C A McMahan; B P Yu
Journal: J Gerontol Date: 1985-11

8. Effects of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice.

Authors: D N Khansari; T Gustad
Journal: Mech Ageing Dev Date: 1991-01 Impact factor: 5.432

Review 9. Human growth hormone and human aging.

Authors: E Corpas; S M Harman; M R Blackman
Journal: Endocr Rev Date: 1993-02 Impact factor: 19.871

10. Dietary modulation of the progression of nephropathy in aging rats: an evaluation of the importance of protein.

Authors: E J Masoro; K Iwasaki; C A Gleiser; C A McMahan; E J Seo; B P Yu
Journal: Am J Clin Nutr Date: 1989-06 Impact factor: 7.045

22 in total

1. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake.

Authors: R Michael Anson; Zhihong Guo; Rafael de Cabo; Titilola Iyun; Michelle Rios; Adrienne Hagepanos; Donald K Ingram; Mark A Lane; Mark P Mattson
Journal: Proc Natl Acad Sci U S A Date: 2003-04-30 Impact factor: 11.205

2. Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration.

Authors: Yoshikazu Chujo; Namiki Fujii; Naoyuki Okita; Tomokazu Konishi; Takumi Narita; Atsushi Yamada; Yushi Haruyama; Kosuke Tashiro; Takuya Chiba; Isao Shimokawa; Yoshikazu Higami
Journal: Age (Dordr) Date: 2012-05-28

10. Role of insulin and growth hormone/insulin-like growth factor-I signaling in lifespan extension: rodent longevity models for studying aging and calorie restriction.

Authors: T Chiba; H Yamaza; I Shimokawa
Journal: Curr Genomics Date: 2007-11 Impact factor: 2.236

Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model.

1. Immunological restoration and anti-tumor effect by Japanese herbal medicine in aged mice.

Review 2. Prolonged longevity of hypopituitary dwarf mice.

3. Differential longevity in mouse stocks selected for early life growth trajectory.

4. Glomerular lesions in mice transgenic for growth hormone and insulinlike growth factor-I. I. Relationship between increased glomerular size and mesangial sclerosis.

5. Immunological enhancement with a low dose of cyclophosphamide in aged mice.

Review 6. Definition and functions of natural killer cells.

7. Nutritional influences on aging of Fischer 344 rats: II. Pathology.

8. Effects of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice.

Review 9. Human growth hormone and human aging.

10. Dietary modulation of the progression of nephropathy in aging rats: an evaluation of the importance of protein.

1. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake.

2. Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration.

Review 3. Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models.

Review 4. Role of insulin-like growth factor binding proteins in mammary gland development.

5. Lymphoid neogenesis and immune infiltration in aged liver.

6. The effects of growth hormone (GH) treatment on GH and insulin/IGF-1 signaling in long-lived Ames dwarf mice.

Review 7. Hormonal control of aging in rodents: the somatotropic axis.

8. Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism.

Review 9. Growth hormone and aging: a challenging controversy.

10. Role of insulin and growth hormone/insulin-like growth factor-I signaling in lifespan extension: rodent longevity models for studying aging and calorie restriction.