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SNP'ing for longevity.

Vijg J - Aging (Albany NY) (2009)

View Article: PubMed Central - PubMed

Affiliation: Albert Einstein College of Medicine, Bronx, NY 10461, USA. jvijg@aecom.yu.edu

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over time to inexorably limits longevity in these species it has been difficult to extrapolate these results to humans... Hence, new model systems need to be found that provide more immediate links to human longevity and healthy aging... control group for single nucleotide variation in the p21 gene... The results amino acid substitution and another in the 3'-untranslated region, that were significantly under-represented among the centenarians... p21 is not as critical a tumor suppressor as p53... mutations have been found in human tumors and p21 knockout mice do not develop possible that one could retain tumor suppressing capability through p53 while SNP variants discovered by Gravina et al. could be an important step on our way to developing interventions to blunt p53's pro-aging actions while retaining its anti-aging effects.

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SNP variants in the p21 gene may attenuate the pro-aging activities of                                    p53 without increasing genome instability and cancer.
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Figure 1: SNP variants in the p21 gene may attenuate the pro-aging activities of p53 without increasing genome instability and cancer.

Mentions: The cyclin-dependent kinase inhibitor p21WAF1/CIP1 is oneof the downstream targets of p53, the so-called guardian of the genome [4]. However, p21 is not as critical a tumor suppressor as p53. Unlike p53, few, if any, p21 mutations have been found in human tumors and p21 knockout mice do not develop many more spontaneous malignancies than their wildtype littermates [5]. Interestingly, evidence has been found that loss of p21 enhances survival of mice with a telomere dysfunction [6]. Hence, p21 may be a promoter of aging, and as such possibly the effector of the pro-aging characteristics of p53 [7]. Constitutive activation of p53 has been demonstrated as a likely cause of premature aging in a number of different mouse models, including animals expressing truncated p53 isoforms [8]. It is possible that one could retain tumor suppressing capability through p53 while simultaneously opposing its pro-aging activity through inhibition of p21 (Figure 1).


SNP'ing for longevity.

Vijg J - Aging (Albany NY) (2009)

SNP variants in the p21 gene may attenuate the pro-aging activities of                                    p53 without increasing genome instability and cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806028&req=5

Figure 1: SNP variants in the p21 gene may attenuate the pro-aging activities of p53 without increasing genome instability and cancer.
Mentions: The cyclin-dependent kinase inhibitor p21WAF1/CIP1 is oneof the downstream targets of p53, the so-called guardian of the genome [4]. However, p21 is not as critical a tumor suppressor as p53. Unlike p53, few, if any, p21 mutations have been found in human tumors and p21 knockout mice do not develop many more spontaneous malignancies than their wildtype littermates [5]. Interestingly, evidence has been found that loss of p21 enhances survival of mice with a telomere dysfunction [6]. Hence, p21 may be a promoter of aging, and as such possibly the effector of the pro-aging characteristics of p53 [7]. Constitutive activation of p53 has been demonstrated as a likely cause of premature aging in a number of different mouse models, including animals expressing truncated p53 isoforms [8]. It is possible that one could retain tumor suppressing capability through p53 while simultaneously opposing its pro-aging activity through inhibition of p21 (Figure 1).

View Article: PubMed Central - PubMed

Affiliation: Albert Einstein College of Medicine, Bronx, NY 10461, USA. jvijg@aecom.yu.edu

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

over time to inexorably limits longevity in these species it has been difficult to extrapolate these results to humans... Hence, new model systems need to be found that provide more immediate links to human longevity and healthy aging... control group for single nucleotide variation in the p21 gene... The results amino acid substitution and another in the 3'-untranslated region, that were significantly under-represented among the centenarians... p21 is not as critical a tumor suppressor as p53... mutations have been found in human tumors and p21 knockout mice do not develop possible that one could retain tumor suppressing capability through p53 while SNP variants discovered by Gravina et al. could be an important step on our way to developing interventions to blunt p53's pro-aging actions while retaining its anti-aging effects.

Show MeSH
Related in: MedlinePlus