LongevityMap Gene

Gene details

HGNC symbol
TP53 
Aliases
P53; BCC7; LFS1; TRP53 
Common name
tumor protein p53 
Description
This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]
Cytogenetic Location
17p13.1
UCSC Genome Browser
View 17p13.1 on the UCSC genome browser
OMIM
191170
Ensembl
ENSG00000141510
UniProt/Swiss-Prot
A0A087WT22_HUMAN
Entrez Gene
7157
UniGene
437460
1000 Genomes
1000 Genomes

Homologs in model organisms

Danio rerio
tp53
Mus musculus
Tp53
Rattus norvegicus
Tp53

In other databases

GenAge model organism genes
  • A homolog of this gene for Mus musculus is present as Trp53
GenAge human genes
  • This gene is present as TP53
CellAge
  • This gene is present as TP53

Studies (37)

Significant/Non-significant: 22/15

Study 1

Longevity Association
Significant
Population
American (Caucasian)
Study Design
A genome-wide linkage scan on human longevity was performed in 279 families with multiple long-lived siblings
Conclusions
One locus on chromosome 3p24-22 had genome-wide significance
Reference

    Study 2

    Longevity Association
    Non-significant
    Population
    American (Caucasian)
    Study Design
    A genome-wide linkage scan on human longevity was performed in 279 families with multiple long-lived siblings
    Conclusions
    One locus on chromosome 9q31-34 was borderline significant and a peak on 12q24 was detected in a subset of the data. There was also modest evidence for a peak on 4q22-25.
    Reference

      Study 3

      Longevity Association
      Significant
      Population
      European
      Study Design
      Genome-wide linkage scan in 2118 European nonagenarian sibships and younger controls from various European studies followed by genome-wide association study in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls
      Conclusions
      Four regions showed linkage to longevity (14q11.2, 17q12-q22, 19p13.3-p13.11 and 19q13.11-q13.32)
      Reference

        Study 4

        Longevity Association
        Significant
        Population
        European
        Study Design
        Genome-wide linkage scan in 2118 European nonagenarian sibships and younger controls from various European studies followed by genome-wide association study in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls
        Conclusions
        Four regions showed linkage to longevity (14q11.2, 17q12-q22, 19p13.3-p13.11 and 19q13.11-q13.32)
        Reference

          Study 5

          Longevity Association
          Significant
          Population
          European
          Study Design
          Genome-wide linkage scan in 2118 European nonagenarian sibships and younger controls from various European studies followed by genome-wide association study in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls
          Conclusions
          Four regions showed linkage to longevity (14q11.2, 17q12-q22, 19p13.3-p13.11 and 19q13.11-q13.32)
          Reference

            Study 6

            Longevity Association
            Significant
            Population
            European
            Study Design
            Genome-wide linkage scan in 2118 European nonagenarian sibships and younger controls from various European studies followed by genome-wide association study in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls
            Conclusions
            Four regions showed linkage to longevity (14q11.2, 17q12-q22, 19p13.3-p13.11 and 19q13.11-q13.32)
            Reference

              Study 7

              Longevity Association
              Significant
              Population
              American (Caucasian)
              Study Design
              Genome-wide scan for linkage in 308 individuals belonging to 137 sibships demonstrating exceptional longevity, predominantly of European descent
              Conclusions
              Significant evidence for linkage was noted for chromosome 4 at D4S1564
              Indentifier
              D4S1564
              Reference

                Study 8

                Longevity Association
                Significant
                Population
                Italian (Central)
                Study Design
                A cross-sectional population study of 1072 individuals (18–106 years old) was performed and TP53 variants were analyzed
                Conclusions
                The variant rs1042522 affects females longevity, showing significant associations with longevity in the comparison of individuals >91 years old with individuals aged 73-91 years old. The TP53 P72 allele is significantly underrepresented in the >91 years old women group.
                Indentifier
                rs1042522
                Reference

                  Study 9

                  Longevity Association
                  Non-significant
                  Population
                  Chinese
                  Study Design
                  Twenty-eight mtDNA haplogroups were studied in 463 individuals with exceptional longevity (>95 years). As controls, 926 individuals aged 60-69 years (elderly group) and 463 individuals aged 40-49 years (middle-aged group) were used.
                  Conclusions
                  M9 haplogroups in longevity subjects were reduced and a decreasing trend of N9 frequency was also observed. An increasing trend of D4 frequency and a decreasing trend of B4a frequency were observed in females. None of the associations were significant, however, after controlling for multiple testing.
                  Reference

                    Study 10

                    Longevity Association
                    Significant
                    Population
                    American (Caucasian)
                    Study Design
                    Genome-wide association study using 1,471 genotyped participants from the Framingham Heart Study, of which 1,173 individuals had known lifespans, plus 517 individuals from the Offspring cohort for validating connections between longevity and genetic variants
                    Conclusions
                    A total of 27 SNPs were identified at the intersection of various statistical procedures
                    Indentifier
                    rs9616906
                    Reference

                      Study 11

                      Longevity Association
                      Significant
                      Population
                      American (Caucasian)
                      Study Design
                      Genome-wide association study using 1,471 genotyped participants from the Framingham Heart Study, of which 1,173 individuals had known lifespans, plus 517 individuals from the Offspring cohort for validating connections between longevity and genetic variants
                      Conclusions
                      A total of 27 SNPs were identified at the intersection of various statistical procedures
                      Indentifier
                      rs13008689
                      Reference

                        Study 12

                        Longevity Association
                        Significant
                        Population
                        American (Caucasian)
                        Study Design
                        Genome-wide association study using 1,471 genotyped participants from the Framingham Heart Study, of which 1,173 individuals had known lifespans, plus 517 individuals from the Offspring cohort for validating connections between longevity and genetic variants
                        Conclusions
                        A total of 27 SNPs were identified at the intersection of various statistical procedures
                        Indentifier
                        rs10819510
                        Reference

                          Study 13

                          Longevity Association
                          Significant
                          Population
                          American (Caucasian)
                          Study Design
                          Genome-wide association study using 1,471 genotyped participants from the Framingham Heart Study, of which 1,173 individuals had known lifespans, plus 517 individuals from the Offspring cohort for validating connections between longevity and genetic variants
                          Conclusions
                          A total of 27 SNPs were identified at the intersection of various statistical procedures.
                          Indentifier
                          rs3120819
                          Reference

                            Study 14

                            Longevity Association
                            Significant
                            Population
                            American (Caucasian)
                            Study Design
                            Genome-wide association study using 1,471 genotyped participants from the Framingham Heart Study, of which 1,173 individuals had known lifespans, plus 517 individuals from the Offspring cohort for validating connections between longevity and genetic variants
                            Conclusions
                            A total of 27 SNPs were identified at the intersection of various statistical procedures
                            Indentifier
                            rs1205035
                            Reference

                              Study 15

                              Longevity Association
                              Non-significant
                              Population
                              Chinese (Guangxi Bama)
                              Study Design
                              The mtDNA of ten bama centenarians were sequenced and seven novel variations were identified. 313 individuals(113 samples in the 90-110 y, 75 between 80-89 y and 125 between 10-79 y) were involved for the analysis of 26 variations in mtDNA D-loop and several serum parameters.
                              Conclusions
                              The frequency of mt146A had no significant difference among the three age groups(90-110 y, 80-89 y and 10-79 y) (P > 0.005), neither with the mt5178A/C polymorphism (P > 0.05)
                              Indentifier
                              mt146A
                              Reference

                                Study 16

                                Longevity Association
                                Non-significant
                                Population
                                English (Newcastle)
                                Study Design
                                The mtDNA haplogroups were studied in 700 more than 85-year-old subjects to identify the association with frailty and mortality
                                Conclusions
                                No association between mtDNA haplogroups and either frailty or survival beyond age 85 or any informative biomarker of aging
                                Reference

                                  Study 17

                                  Longevity Association
                                  Non-significant
                                  Population
                                  American (Utah)
                                  Study Design
                                  A whole-genome scan for genetic linkage was performed in 325 individuals who exhibited high levels of both familial longevity and individual longevity
                                  Conclusions
                                  There were no significant results after correcting for multiple testing. The strongest signal was observed in marker D3S3547, in 3p24.1, and other suggestive peaks were observed in 18q23-24, 8q23, and 17q21.
                                  Indentifier
                                  D3S3547
                                  Reference

                                    Study 18

                                    Longevity Association
                                    Non-significant
                                    Population
                                    American (Utah)
                                    Study Design
                                    A whole-genome scan for genetic linkage was performed in 325 individuals who exhibited high levels of both familial longevity and individual longevity
                                    Conclusions
                                    There were no significant results after correcting for multiple testing. The strongest signal was observed in marker D3S3547, in 3p24.1, and other suggestive peaks were observed in 18q23-24, 8q23, and 17q21.
                                    Reference

                                      Study 19

                                      Longevity Association
                                      Non-significant
                                      Population
                                      American (Utah)
                                      Study Design
                                      A whole-genome scan for genetic linkage was performed in 325 individuals who exhibited high levels of both familial longevity and individual longevity
                                      Conclusions
                                      There were no significant results after correcting for multiple testing. The strongest signal was observed in marker D3S3547, in 3p24.1, and other suggestive peaks were observed in 18q23-24, 8q23, and 17q21.
                                      Reference

                                        Study 20

                                        Longevity Association
                                        Non-significant
                                        Population
                                        American (Utah)
                                        Study Design
                                        A whole-genome scan for genetic linkage was performed in 325 individuals who exhibited high levels of both familial longevity and individual longevity
                                        Conclusions
                                        There were no significant results after correcting for multiple testing. The strongest signal was observed in marker D3S3547, in 3p24.1, and other suggestive peaks were observed in 18q23-24, 8q23, and 17q21.
                                        Reference

                                          Study 21

                                          Longevity Association
                                          Non-significant
                                          Population
                                          Chinese (Han)
                                          Study Design
                                          556 longevous individuals (354 females, 90-108 years, mean ± SD: 94.59 ± 3.34 years) and 403 unrelated controls (199 females, 22-73 years, mean ± SD: 56.24 ± 7.81 years) were examined for the association between mtDNA C150T and longevity
                                          Conclusions
                                          There was no significant association between C150T and longevity even when mtDNA haplogroups defined by C150T and gender were taken into account
                                          Indentifier
                                          MtC150T
                                          Reference

                                            Study 22

                                            Longevity Association
                                            Significant
                                            Population
                                            Japanese
                                            Study Design
                                            The correlation between mitochondrial polymorphisms and the longevity phenotype was analyzed in 112 Japanese semi-supercentenarians and 672 previous published sequences from individuals with non-disease phenotypes
                                            Conclusions
                                            mtSNP 14979C (Cytb: Ile78Thr) in D4a was identified to be correlated with extreme longevity
                                            Indentifier
                                            14979C
                                            Reference

                                              Study 23

                                              Longevity Association
                                              Significant
                                              Population
                                              Finnish
                                              Study Design
                                              The frequencies of mtDNA haplogroups and haplogroup clusters were examined among elderly subjects and controls in a Finnish population: 225 persons aged 90 or 91 years (Vitality 90+, 179 women, 400 mid-age controls (18–65 years; mean age: 40.5 years)) and 257 infants (2–12 months; mean: 6.5 months))
                                              Conclusions
                                              Haplogroup H was less frequent among the Vitality 90+ cases than among the middle-aged subjects (P=0.001) and infants (P=0.00001), whereas haplogroups J, U and K were more frequent. Haplogroup clusters also differed between Vitality 90+ and both the middle-aged subjects (P=0.002) and infants (P=0.00001), the frequency of haplogroup cluster HV being lower in the former and that of UK and WIX being higher. MtDNA haplogroups or haplogroup clusters were associated with longevity.
                                              Reference

                                                Study 24

                                                Longevity Association
                                                Significant
                                                Population
                                                Italian
                                                Study Design
                                                Inherited mtDNA markers were analyzed between a sample of individuals selected for successful aging and longevity (212 subjects older than 100 years and in good clinical condition) and a sample of 275 younger individuals (20–75 years, median age 38 years) carefully matched as to sex and geographic origin
                                                Conclusions
                                                Male centenarians emerged in northern Italy as a particular sample: 1) mtDNA haplogroup frequency distribution was different between centenarians and younger individuals (P=0.017 by permutation tests); and 2) the frequency of the J haplogroup was notably higher in centenarians than in younger individuals (P=0.0052 by Fisher exact test). MtDNA inherited variability could play a role in successful aging and longevity.
                                                Reference

                                                  Study 25

                                                  Longevity Association
                                                  Significant
                                                  Population
                                                  Danish
                                                  Study Design
                                                  Participants (n = 9,219) of the Copenhagen City Heart Study were genotyped for the p53 Arg72Pro polymorphism. Then the morbidity of 6 subtypes of cancer and mortality were assessed for each genotype.
                                                  Conclusions
                                                  The risk of hematologic cancer increased 2-fold in Arg/Pro heterozygotes vs. Arg/Arg homozygotes (p < 0.001), with a similar trend in Pro/Pro homozygotes. The overall 12-year survival after blood sampling was increased in Arg/Pro heterozygotes with 3% (p = 0.003) and in Pro/Pro homozygotes with 6% (p = 0.002) vs. Arg/Arg homozygotes. The cumulative 5-year mortality after a cancer diagnosis was reduced in Arg/Pro heterozygotes and Pro/Pro homozygotes vs. Arg/Arg homozygotes by 9% (p = 0.003) and 13% (p = 0.03). These results suggest a better prognosis in Arg/Pro heterozygotes and Pro/Pro homozygotes vs. Arg/Arg homozygotes after the diagnosis of cancer or other life-threatening disease.
                                                  Indentifier
                                                  rs1042522
                                                  Reference

                                                    Study 26

                                                    Longevity Association
                                                    Significant
                                                    Population
                                                    Italian (Northern)
                                                    Study Design
                                                    The rs1333049 polymorphism was examined in a sample of 80 healthy centenarians (100-104y, 41 females), 218 patients younger than 40 who had experienced an acute myocardial infarction (22-39y, 53 females), and a control group of 258 healthy young volunteers (22–39y, 120 females) matched to acute myocardial infarction patients for age and sex
                                                    Conclusions
                                                    The frequency of the C allele of rs1333049 was significantly lower in centenarians compared to young controls, whereas acute myocardial infarction patients showed a higher frequency. After adjustment for gender and vascular risk factors, the C allele of rs1333049 remained significantly associated with a reduced likelihood to reach longevity: Odds ratio 0.64, 95% confidence interval (CI) 0.39-0.89, p < 0.01. The rs1333049 polymorphism may influence successful longevity, possibly by modulating the risk of age-related disorders.
                                                    Indentifier
                                                    rs1333049
                                                    Reference

                                                      Study 27

                                                      Longevity Association
                                                      Significant
                                                      Population
                                                      European (Danish, Finnish, South Italian and Greek)
                                                      Study Design
                                                      mtDNA sequences were analyzed in 4239 European individuals. 1292 individuals (646 ultranonagenarians and 646 controls) were selected for complete sequencing. The mtDNA subhaplogroups were determined in remaining 2947 samples (1449 ultranonagenarians and 1498 controls) to verify possible haplogroup association with longevity and the distribution pattern among European counties.
                                                      Conclusions
                                                      The distribution of H2, T2 haplogroup in female and H1, J2 in male showed differences between older subjects and younger controls, but no association was detectable when corrected for multiple test. Mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes.
                                                      Reference

                                                        Study 28

                                                        Longevity Association
                                                        Significant
                                                        Population
                                                        Spanish
                                                        Study Design
                                                        Allele and genotype distributions of rs1333049 were compared in centenarians and younger adults (without (healthy) or with CAD) in two independent cohorts: Spanish and Japanese.
                                                        Conclusions
                                                        The frequency of the GG genotype in centenarians was higher than either healthy or CAD controls in Spanish. In the Japanese cohort, C allele did not differ between centenarians and healthy controls, but it was significantly lower in centenarians than in CAD controls.
                                                        Indentifier
                                                        rs1333049
                                                        Reference

                                                          Study 29

                                                          Longevity Association
                                                          Significant
                                                          Population
                                                          Japanese
                                                          Study Design
                                                          Allele and genotype distributions of rs1333049 were compared in centenarians and younger adults (without (healthy) or with CAD) in two independent cohorts: Spanish and Japanese.
                                                          Conclusions
                                                          The frequency of the GG genotype in centenarians was higher than either healthy or CAD controls in Spanish. In the Japanese cohort, C allele did not differ between centenarians and healthy controls, but it was significantly lower in centenarians than in CAD controls.
                                                          Indentifier
                                                          rs1333049
                                                          Reference

                                                            Study 30

                                                            Longevity Association
                                                            Significant
                                                            Population
                                                            Italian (Northern)
                                                            Study Design
                                                            GSTT1 (Glutathione S-transferase theta 1) deletion and the simultaneous presence of the three p53 polymorphisms were examined in 66 nonagenarians and centenarians in good health and in a sample of 150 young healthy volunteers of the same ethnic group
                                                            Conclusions
                                                            No significant differences were found for individual genes. However, the absence of any p53 polymorphisms and of GSTT1 deletion, and the simultaneous presence of the three p53 polymorphisms and of GSTT1 deletion, were much more frequent in young subjects than in centenarians (41.5% versus 26.9% and 8.8% versus 3.8%, respectively).
                                                            Indentifier
                                                            TP53
                                                            Reference

                                                              Study 31

                                                              Longevity Association
                                                              Non-significant
                                                              Population
                                                              German
                                                              Study Design
                                                              Genome-wide association study comparing 664,472 autosomal SNPs in 763 long-lived individuals (mean age: 99.7 years) and 1085 controls (mean age: 60.2 years). Top SNPs from the GWAS were further investigated in an independent German sample comprised of 754 long-lived individuals (mean age: 96.9 years) and 860 controls (mean age: 67.3 years).
                                                              Conclusions
                                                              Fifteen SNPs had indicative association with longevity, even if not statistically significant after correcting for multiple hypothesis testing. None of these SNPs were validated in the follow-up analysis. Since rs12741354 (in ASTN1) was nearly significant, it was further investigated in French centenarians but it failed to be associated with longevity.
                                                              Reference

                                                                Study 32

                                                                Longevity Association
                                                                Non-significant
                                                                Population
                                                                Italian (Southern)
                                                                Study Design
                                                                A two-stage case-control study was performed to identify the association between longevity and variation of in homeostasis regulation pathway genes. 317 SNPs in 104 genes were analyzed in 78 cases (≥90 years, median age 98 years, 42 females) and 71 controls (<90 years, median age 67 years, 32 females) in stage 1. Then, 31 candidate SNPs identified in stage 1 (π markers = 0.1) were analyzed in an independent sample composed by 288 cases (≥90 years, median age 92 years, 163 females) and 554 controls (<90 years, median age 67 years, 277 females).
                                                                Conclusions
                                                                After adjustment for multiple testing, no significant association was identified between various SNPs and longevity.
                                                                Reference

                                                                  Study 33

                                                                  Longevity Association
                                                                  Significant
                                                                  Population
                                                                  Irish
                                                                  Study Design
                                                                  Polymorphic restriction enzyme sites within a 2643 bp region of mtDNA were identified by PCR-RFLP in 129 aged individuals (80- 97y, 70% female) and 100 controls (19- 45y, 59% female). Then, genetic haplotypes for a healthy aged and a younger control cohort of patients was constructed to find out the relationship between longevity and mtDNA polymorphisms.
                                                                  Conclusions
                                                                  The were no significant frequency differences between the two age groups for 46 identified haplotypes. However, the branch of haplotypes defined by 16389g displayed a significant increased frequency in the aged samples (P=0.015). Inversely, the branch of haplotypes defined by 16000g displayed a significant decreased frequency in the aged samples (P=0.011).
                                                                  Indentifier
                                                                  16389g
                                                                  Reference

                                                                    Study 34

                                                                    Longevity Association
                                                                    Non-significant
                                                                    Population
                                                                    Irish
                                                                    Study Design
                                                                    Polymorphic restriction enzyme sites within a 2643 bp region of mtDNA were identified by PCR-RFLP in 129 aged individuals (80- 97y, 70% female) and 100 controls (19- 45y, 59% female). Then, genetic haplotypes for a healthy aged and a younger control cohort of patients was constructed to find out the relationship between longevity and mtDNA polymorphisms.
                                                                    Conclusions
                                                                    The were no significant frequency differences between the two age groups for 46 identified haplotypes. The previously reported longevity associated European J haplogroup was not found at an increased frequency within the Irish aged population (P=0.36). The polymorphism (mt5178A) associated with longevity in the Japanese was not found in the Irish population, while the polymorphism (mt9055A) associated with successful ageing in French centenarians was found at a noticeable but not significant (P=0.164) increased frequency in the Irish aged population compared to the younger control group.
                                                                    Indentifier
                                                                    mt9055A
                                                                    Reference

                                                                      Study 35

                                                                      Longevity Association
                                                                      Non-significant
                                                                      Population
                                                                      Danish
                                                                      Study Design
                                                                      592 SNPs from 77 genes involved in nine sub-processes were analyzed in 1089 long-lived and 736 middle-aged Danes. Then, a replicated study was carried out in a German cohort.
                                                                      Conclusions
                                                                      The results did not remain significant after correction. The findings drawn from the Danish cohort were not replicated in German samples.
                                                                      Indentifier
                                                                      rs9894946
                                                                      Reference

                                                                        Study 36

                                                                        Longevity Association
                                                                        Non-significant
                                                                        Population
                                                                        American (Caucasian)
                                                                        Study Design
                                                                        A genome-wide linkage scan on human longevity was performed in 279 families with multiple long-lived siblings
                                                                        Conclusions
                                                                        One locus on chromosome 9q31-34 was borderline significant and a peak on 12q24 was detected in a subset of the data. There was also modest evidence for a peak on 4q22-25.
                                                                        Reference

                                                                          Study 37

                                                                          Longevity Association
                                                                          Non-significant
                                                                          Population
                                                                          American (Caucasian)
                                                                          Study Design
                                                                          A genome-wide linkage scan on human longevity was performed in 279 families with multiple long-lived siblings
                                                                          Conclusions
                                                                          One locus on chromosome 9q31-34 was borderline significant and a peak on 12q24 was detected in a subset of the data. There was also modest evidence for a peak on 4q22-25.
                                                                          Reference