TY - JOUR
T1 - Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span
AU - Bauer, Johannes H.
AU - Poon, Peter C.
AU - Glatt-Deeley, Heather
AU - Abrams, John M.
AU - Helfand, Stephen L.
N1 - Funding Information:
The authors would like to thank R.A. Reenan and J. Jack for critical reading of the manuscript and H. Keshishian, R. Davis, K. Basler, M. Tatar, and the Drosophila Stock Center (Bloomington) for fly stocks. We thank S. Kowalski, S. Goupil, and A. Sanchez-Blanco for technical assistance. This work was supported by grants from the NIA (AG16667, AG24353), the Donaghue Foundation, and the Ellison Medical Foundation to S.L.H. S.L.H. is an Ellison Medical Research Foundation Senior Investigator. This research was conducted while J.H.B. was a Glenn/AFAR Postdoctoral Fellow.
PY - 2005/11/22
Y1 - 2005/11/22
N2 - Hyperactivation of p53 leads to a reduction in tumor formation and an unexpected shortening of life span in two different model systems [1, 2]. The decreased life span occurs with signs of accelerated aging, such as osteoporosis, reduction in body weight, atrophy of organs, decreased stress resistance, and depletion of hematopoietic stem cells. These observations suggest a role for p53 in the determination of life span and the speculation that decreasing p53 activity may result in positive effects on some aging phenotypes [3, 4]. In this report, we show that expression of dominant-negative versions of Drosophila melanogaster p53 in adult neurons extends life span and increases genotoxic stress resistance in the fly. Consistent with this, a naturally occurring allele with decreased p53 activity has been associated with extended survival in humans [5]. Expression of the dominant-negative Drosophila melanogaster p53 constructs does not further increase the extended life span of flies that are calorie restricted, suggesting that a decrease in p53 activity may mediate a component of the calorie-restriction life span-extending pathway in flies.
AB - Hyperactivation of p53 leads to a reduction in tumor formation and an unexpected shortening of life span in two different model systems [1, 2]. The decreased life span occurs with signs of accelerated aging, such as osteoporosis, reduction in body weight, atrophy of organs, decreased stress resistance, and depletion of hematopoietic stem cells. These observations suggest a role for p53 in the determination of life span and the speculation that decreasing p53 activity may result in positive effects on some aging phenotypes [3, 4]. In this report, we show that expression of dominant-negative versions of Drosophila melanogaster p53 in adult neurons extends life span and increases genotoxic stress resistance in the fly. Consistent with this, a naturally occurring allele with decreased p53 activity has been associated with extended survival in humans [5]. Expression of the dominant-negative Drosophila melanogaster p53 constructs does not further increase the extended life span of flies that are calorie restricted, suggesting that a decrease in p53 activity may mediate a component of the calorie-restriction life span-extending pathway in flies.
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U2 - 10.1016/j.cub.2005.10.051
DO - 10.1016/j.cub.2005.10.051
M3 - Article
C2 - 16303568
AN - SCOPUS:27844596799
SN - 0960-9822
VL - 15
SP - 2063
EP - 2068
JO - Current Biology
JF - Current Biology
IS - 22
ER -