Originally published as Genetics Published Articles Ahead of Print on September 30, 2004.

Genetics, Vol. 169, 265-274, January 2005, Copyright © 2005
doi:10.1534/genetics.104.032292

The Influence of Genes on the Aging Process of Mice

A Statistical Assessment of the Genetics of Aging

João Pedro de Magalhães*,1, José A. S. Cabral{dagger} and Domingos Magalhães{ddagger}

* Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115
{dagger} FEUP, University of Porto, 4150-564 Porto, Portugal
{ddagger} FLUP, University of Porto, 4200-465 Porto, Portugal

1 Corresponding author: Department of Genetics, Harvard Medical School, 77 Ave. Louis Pasteur, Room 238, Boston, MA 02115.
E-mail: jp@senescence.info

Genetic interventions that accelerate or retard aging in mice are crucial in advancing our knowledge over mammalian aging. Yet determining if a given intervention affects the aging process is not straightforward since, for instance, many disease-causing mutations may decrease life span without affecting aging. In this work, we employed the Gompertz model to determine whether several published interventions previously claimed to affect aging in mice do indeed alter the aging process. First, we constructed age-specific mortality tables for a number of mouse cohorts used in longevity experiments and calculated the rate at which mortality increases with age. Estimates of age-independent mortality were also calculated. We found no statistical evidence that GHRHR, IGF1R, INSR, PROP1, or TRX delay or that ATM + TERC, BubR1, klotho, LMNA, PRDX1, p53, WRN + TERC, or TOP3B accelerate mouse aging. Often, changes in the expression of these genes affected age-independent mortality and so they may prove useful to other aspects of medicine. We found statistical evidence that C/EBP, MSRA, SHC1, growth hormone, GHR, PIT1, and PolgA may influence aging in mice. These results were interpreted together with age-related physiological and pathological changes and provide novel insights regarding the role of several genes in the mammalian aging process.




This article has been cited by other articles:


Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
J. P. d. Magalhaes, J. Costa, and G. M. Church
An Analysis of the Relationship Between Metabolism, Developmental Schedules, and Longevity Using Phylogenetic Independent Contrasts
J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2007; 62(2): 149 - 160.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. S. Bonkowski, J. S. Rocha, M. M. Masternak, K. A. Al Regaiey, and A. Bartke
From the Cover: Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction
PNAS, May 16, 2006; 103(20): 7901 - 7905.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Bartke
Minireview: Role of the Growth Hormone/Insulin-Like Growth Factor System in Mammalian Aging
Endocrinology, September 1, 2005; 146(9): 3718 - 3723.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
W. E. Sonntag, C. S. Carter, Y. Ikeno, K. Ekenstedt, C. S. Carlson, R. F. Loeser, S. Chakrabarty, S. Lee, C. Bennett, R. Ingram, et al.
Adult-Onset Growth Hormone and Insulin-Like Growth Factor I Deficiency Reduces Neoplastic Disease, Modifies Age-Related Pathology, and Increases Life Span
Endocrinology, July 1, 2005; 146(7): 2920 - 2932.
[Abstract] [Full Text] [PDF]

Home page
 Sci Aging Knowl EnvironHome page
Papers of Note
Sci. Aging Knowl. Environ., February 2, 2005; 2005(5): nw5 - nw5.
[Full Text]