Results: Characteristics of participants of the HHP and HAAS study population at the 1991-1993 examination when blood was drawn for genotyping in the present study (Exam 4 of the cohort). The more limited set of parameters recorded at Exam 1 (1965-1968) is also shown. Unadjusted data are shown in Supplementary Table S1. Presented are biological characteristics, general health status, disease prevalence, and functional status of long-lived cases (longevity phenotype) and average-lived controls (average phenotype). The long-lived cases were older, leaner (based on lower waist:hip ratio), had lower plasma glucose level, lower plasma insulin level, better self-rated health, and lower prevalence of cardiovascular disease (hypertension, coronary heart disease, and stroke) and cancer. The cases appeared better able to walk 0.8 km than controls, but grip strength was similar. Cognitive score was slightly higher in cases. When adjusting for age, the differences between long-lived cases became even starker.

Discussion: The present nested case-control study found no association of genetic variation in mTOR pathway genes MTOR, RPTOR, RICTOR, and RPS6KA1 with longevity (survival to age 95 years or older) in American men of Japanese ancestry.

Table 1. Age-Adjusted Baseline Characteristics of Case and Control Participants (mean ± SD)

Parameter Controls Cases p n 374 439 Biological and physiological phenotypes Height (cm) at Exam 1 163.2 ± 5.4 162.8 ± 5.4 .38 Height (cm) at Exam 4 161.2 ± 5.6 161.3 ± 5.5 .96 Weight (kg) at Exam 1 64.1 ± 9.4 62.0 ± 7.9 .009 Weight (kg) at Exam 4 59.6 ± 9.6 61.6 ± 8.0 .020 BMI (kg/m2) at Exam 1 24.2 ± 3.0 23.5 ± 2.7 .016 BMI (kg/m2) at Exam 4 23.0 ± 3.1 23.6 ± 2.9 .040 BMI at age 25 24.0 ± 3.0 23.4 ± 2.7 .016 Waist:hip ratio 0.95 ± 0.06 0.94 ± 0.05 .015 Systolic BP (mmHg) at Exam 1 135.1 ± 18.8 128.7 ± 18.3 .000 Systolic BP (mmHg) at Exam 4 151.0 ± 26.3 150.4 ± 22.4 .79 Diastolic BP (mmHg) at Exam 1 83.1 ±11.8 81.2 ±10.5In the lower legs, the blood pressure (BP) was compared to the BP in the arms. BMI refers to body mass index, CASI to cognitive abilities screening instrument (score range: 1-100), CHD to coronary heart disease, COPD to chronic obstructive pulmonary disease (emphysema), EHT to essential hypertension (moderate: systolic/diastolic BP 140-160 mmHg/90-95 mmHg or on antihypertensive medication; severe: systolic/diastolic BP >160/>95 mmHg or on antihypertensive medication), HDL to high-density lipoprotein, HOMA to homeostasis model assessment, ISH to isolated systolic hypertension (moderate: systolic BP 140-160 mmHg; severe: systolic BP >160 mmHg), and LDL to low-density lipoprotein. The percent of chi-square values that fell beyond these limits was actually less than expected: 8.6%, 1.2%, and 0%. For minor allele frequencies of 0.1-0.4 and a nominal significance level of 0.05, the study had 90% power to detect odds ratios ranging from 1.58-1.95 and 99% power to detect odds ratios of 1.83-2.36. Therefore, although almost all ancestry SNPs with at least moderate effects on longevity will create an excess of high chi-square test values, we noted a deficiency in such values (Tables 2-4). There were 81 tests for association between genetic variants (2df) and case-control status. The quantiles of chi-square for the upper 2df 10%, 5%, and 1% percentiles are 4.61, 5.99, and 9.21, respectively.

Table 2. Frequency of Minor Allele of Each Tagging SNP of MTOR on Chromosome 1p36 in Long-Lived Case vs Control Participants

Total Number of Minor Allele Frequency of SNP ID Position Cases and Controls Cases and Controls, % (95% CI) chi-square p-value 
rs1057079 11205058 440/374 12.6 and 12.8 (0.035 to 0.030) 1.42 0.49 
rs11581010 11212458 440/374 10.7 and 11.1 (0.035 to 0.026) 0.36 0.84 
rs3806317 11248216 440/374 13.8 and 15.2 (0.049 to 0.019) 0.81 0.67 
rs11121703 11293792 439/374 13.9 and 15.4 (0.049 to 0.020) 1.65 0.44 
rs4845858 11304720 439/372 19.0 and 18.3 (0.031 to 0.045) 0.63 .73 
rs3765904 11321864 440/374 7.3 and 7.4 (0.026 to 0.025) 1.22 .54 

Notes: We captured all alleles at r2 > .8, i.e., we captured all alleles, and the mean of maximum r2 was .97 for the six tagSNPs.
CI = confidence interval; SNP = single-nucleotide polymorphism.

Table 3. Frequency of Minor Allele of Each Tagging SNP of RPTOR on Chromosome 17p25.3 in Long-Lived Case vs Control Participants

Total Number of Minor Allele Frequency of SNP ID Position Cases and Controls Cases and Controls, % (95% CI) chi-square p-value 
rs4889856 78513632 436/366 33.3 and 34.8 (0.062 to 0.031) 3.70 .16 
rs8064502 78562434 440/374 36.4 and 31.7 (0.001 to 0.093) 4.01 .14 
rs4890052 78564245 438/371 34.0 and 36.4 (0.070 to 0.023) 2.68 .26 
rs7220588 78598231 437/371 34.3 and 37.1 (0.074 to 0.019) 2.91 .23 
rs901065 78599655 425/360 35.3 and 31.9 (0.013 to 0.080) 2.89 .24 
rs8066867 78620072 430The text appears to be a table with some notes and additional information provided. As an AI language model, I do not have enough context to know what type of data is being presented or how it should be improved. Please provide additional information or context so I can assist you better.several limitations to our study that should be noted. Firstly, we only studied men, so it is unclear whether the genotypes of the SNPs tested are associated with longevity or other aging-related phenotypes in women. Secondly, the cases and controls were from different cities, although the authors claim that population substructure differences were not detected. Thirdly, participants were genotyped at different times and centers using different Illumina platforms, which could introduce artifacts into the findings. Fourthly, there was bias in the selection of controls because only their deaths qualified them for control status, which was unavoidable.