Limits...
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

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The large variation in maximum life span among species points toward genetic factors that specify the mechanisms that protect against aging and disease... Unfortunately, since little is known about the aging phenotypes that emerge 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... Gravina et al. put this hypothesis to the test by genotyping a population of Italian centenarians and a younger, control group for single nucleotide variation in the p21 gene... The results revealed at least two rare variants, one in the coding regions leading to an amino acid substitution and another in the 3'-untranslated region, that were significantly under-represented among the centenarians... 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... Interestingly, evidence has been found that loss of p21 enhances survival of mice with a telomere dysfunction... Hence, p21 may be a promoter of aging, and as such possibly the effector of the pro-aging characteristics of p53... 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)... Based on the above, it is conceivable that variations in p21 may affect its dual role in aging and cancer, shifting the balance to its pro-aging capacity while retaining robust tumor suppression... If followed up by functional studies, the 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

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
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).


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.

The large variation in maximum life span among species points toward genetic factors that specify the mechanisms that protect against aging and disease... Unfortunately, since little is known about the aging phenotypes that emerge 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... Gravina et al. put this hypothesis to the test by genotyping a population of Italian centenarians and a younger, control group for single nucleotide variation in the p21 gene... The results revealed at least two rare variants, one in the coding regions leading to an amino acid substitution and another in the 3'-untranslated region, that were significantly under-represented among the centenarians... 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... Interestingly, evidence has been found that loss of p21 enhances survival of mice with a telomere dysfunction... Hence, p21 may be a promoter of aging, and as such possibly the effector of the pro-aging characteristics of p53... 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)... Based on the above, it is conceivable that variations in p21 may affect its dual role in aging and cancer, shifting the balance to its pro-aging capacity while retaining robust tumor suppression... If followed up by functional studies, the 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