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Parental longevity and polygenic longevity scores in relation to ageing-related factors in a population of 70-year-olds followed over six years: The Gothenburg H70 Birth Cohort Study.

As societies age, a deeper understanding of ageing-related factors that contribute to longevity is needed. We therefore investigated possible longevity factors (social, medical, and biological) in relation to parental longevity (PL) and polygenic longevity scores (PGLSs). We examined 1126 70-year-olds from the Swedish population-based Gothenburg H70 Birth Cohort study in 2014-2016 (response rate 72%), with follow-up in 2019-2022 (response rate 77.6%). Comprehensive examinations included self-reported information on parents' ages, socioeconomic factors, mental, cardiovascular, and neurological health, anthropometry, laboratory data, and genotyping to construct two continuous PGLSs variables (with and without the APOE locus). PL groups were categorised as high if both parents survived to age 85 (17.2%); medium if one parent had survived (43.3%), and low if neither parent had survived to age 85 (39.4%). Higher PL and higher PGLSs were related to less hypertension, higher educational level, better childhood, and current socioeconomic status. In addition, higher PL was associated with higher MMSE score, total cholesterol, HDL-cholesterol (HDL-c) and LDL-cholesterol (LDL-c), lower BMI, homocysteine and inflammatory markers (IL-6, CRP) levels, and less smoking, whereas higher PGLSs was related to less myocardial infarction. At follow-up, high-PL was associated with less increase in plasma pTau217. PGLSs were mainly related to socioeconomic and cardiovascular factors, while individuals with long-lived parents, in addition, had several other characteristics of longevity, such as less inflammation, homocysteine, and markers of dementia. PL may be a proxy for biological ageing and used as a screening for ageing-related disorders in the context of prevention.

APOE↗

Parental longevity and survival in elderly patients with Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: In general, elderly patients with Hodgkin's lymphoma (HL) have a less favorable prognosis than younger patients. Factors such as inadequate therapy often due to decreased tolerance to treatment, presence of intercurrent diseases and accumulation of certain clinical and biological risk factors contribute to the poor outcome. Established predictors of prognosis in HL are less appropriate in the elderly population. Consequently, there is a need for additional markers to guide treatment decisions and to improve prediction of outcome. In the general population, the expected length of life of an individual is intimately associated with that of his/her parents. In a small cohort of elderly HL patients, we had previously observed high familial life-span of two previous generations predicts superior survival. The aim of this study was to test the hypothesis that parental longevity alone--an easily accessible and non-disease associated variable--is also associated with improved outcome using an enlarged series of elderly HL patients. DESIGN AND METHODS: One hundred and twenty-one patients with HL >60 years at diagnosis were included. The median follow-up time was 67 (range 37-175) months. Data regarding age at death and reported cause of death were available through parish offices for 228 (94%) parents. The effect of parental lifespan on HL survival included the use of Kaplan-Meier curves and Cox' proportional hazards regression analysis. RESULTS: Maternal as well as paternal lifespan correlated poorly with HL survival, both with regard to overall and disease-specific survival. There was, however, a tendency towards a decreased risk of dying among patients with low maternal lifespan (all-cause mortality: RR=0.7, 95% CI 0.5-1.0). INTERPRETATION AND CONCLUSIONS: Parental longevity does not predict superior survival in elderly patients with HL.

Adult↗

Parental longevity, carotid atherosclerosis, and aortic arterial stiffness in adult offspring.

BACKGROUND AND PURPOSE: We examined the associations of parental longevity with carotid intima-media thickness, carotid plaques, and aortic arterial stiffness in adult offspring. METHODS: A population of 1117 volunteers who participated in the SUVIMAX Vascular Study (mean age, 59.7 years; 49.0% women) were included. Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid B-mode ultrasound examination included measurements (at sites free of plaque) of intima-media thickness at the common carotid arteries and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: The prevalence of carotid plaques in subjects whose fathers had died at <65 years, in those whose fathers were alive at 65 years but who had died by 80 years, and in those whose fathers were alive at 80 years was 40.4%, 30.4%, and 28.9%, respectively (P<0.001). The multivariate odds ratios of carotid plaques in the 3 groups of paternal longevity, adjusted for conventional cardiovascular risk factors, were 1, 0.68 (95% CI, 0.48 to 0.96), and 0.69 (95% CI, 0.49 to 0.98), respectively. The mean common carotid arteries intima-media thickness was higher in subjects with premature paternal death in univariate (P<0.007) but not in multivariate (P=0.39) analyses. Mean PWV decreased with increasing paternal longevity in both univariate and multivariate analyses. The multivariate-adjusted means of PWV in the 3 groups of paternal longevity were 11.9+/-0.14, 11.7+/-0.12, and 11.0+/-0.12 m/s (P<0.0001), respectively. In contrast, neither B-mode ultrasound measurements nor PWV measurements were associated with maternal longevity. CONCLUSIONS: These results may indicate that there are modifications of structure and function of large arteries according to paternal longevity.

Aged↗

Correlation of parents' longevity with carotid intima-media thickness in patients attending a Lipid Clinic.

The relationship between carotid intima-media thickness (IMT) and the subject's parents' longevity has been investigated. The association between parents' age at death and IMT was estimated in 593 consecutive patients attending a Lipid Clinic by survival-analysis methods. Average maximum IMT (Avg-IMT), maximum IMT (Max-IMT), clinical and laboratory variables and parental age at death, were assessed. Kaplan-Meier analyses showed significant differences in survival curves, low IMTs being associated with long-lived parents (p=0.0003 and 0.001 by log-rank test for fathers and mothers, respectively). A Cox proportional hazards regression model showed that higher carotid IMT values were associated with father's and mother's deaths at an early age, even after adjusting for conventional cardiovascular risk factors. These data were confirmed after the stratification of patients into younger (<65 y) and older (>/=65 y) or into subjects with and without a family history of dyslipidemia or vascular diseases. In addition, by stratifying subjects into those with no, one or two long-lived parents, we observed a significant trend for the combination of father's and mother's longevity on their offspring's IMTs (p<0.01 and 0.05 for Avg-IMT and Max-IMT, respectively). These data highlight a significant relationship between carotid artery IMT and a familial predisposition to be long-lived that is independent of the individual's vascular risk profile.

Adolescent↗

Can parental longevity and self-rated life expectancy predict mortality among older persons? Results from an Australian cohort.

This study examined the effects of parental longevity and self-rated life expectancy on mortality, building upon the established model of self-rated health predicting mortality. A community sample of Australians aged 70 and over was surveyed in 1992 and 1995. The associations of interest were examined separately by sex using weighted multiple logistic regression. Parental ages at death were not associated with mortality for either men or women. In multivariate models, self-rated life expectancy had an independent effect on men's mortality and did not reduce the effect of self-rated health on mortality. Our findings from Australia are consistent with results from many countries; the effect of self-rated health on mortality is stronger for men than for women. We also found that the effect of self-rated life expectancy on mortality is stronger for men than for women. The independent effects of self-rated health and self-rated life expectancy indicate a need for a more detailed search for explanatory mechanisms.

Aged↗

Parental longevity and mortality amongst Japanese men and women: the JACC Study.

OBJECTIVES: To examine whether the risk of mortality varies according to parents' age at death. DESIGN AND SUBJECTS: A large prospective study in Japanese men and women from 45 communities across Japan. A total of 51 485 men and women aged 40-79 years completed self-administered questionnaires at baseline and followed up for 9.6 years. RESULTS: The risk of mortality from stroke, cardiovascular disease, and all causes was 20-30% lower in men and women with fathers who died at age > or = 80 years, compared with those with fathers whose age at death was <60 years. A similar reduction was found when the age at death of mothers was > or = 85 years compared with <65 years. Furthermore, the risk reduction was more evident amongst persons with both parents being long-lived parents compared with those with being short-lived parents, especially for death from cardiovascular disease. CONCLUSIONS: Our findings indicate that parental longevity could be a predictor for reduced risk of mortality from stroke, cardiovascular disease, and all causes for both Japanese men and women.

Adult↗

Parental longevity and 7-year changes in blood pressures in adult offspring.

In this report, we examined the cross-sectional and the 7-year longitudinal changes in blood pressures in adult offspring according to parental longevity. A population of volunteers free of symptomatic cardiovascular diseases who participated to the Supplementation en Vitamines et en Minéraux Antioxydants (SUVIMAX) Vascular Study (mean age 52.3 years; 48.3% women) were examined at baseline and 7 years later. Paternal (n=994) and maternal (n=896) longevity were analyzed separately. The prevalence of hypertension at baseline in subjects whose father died at <65 years of age, in those whose fathers were alive by age 65 but died by 80 years of age, and in those whose fathers were alive by age 80 was respectively 34.9%, 28.5%, and 20.2% (P<0.001). The means of systolic blood pressure in the 3 groups of paternal longevity were respectively 128.4 (+/-16.0), 125.3 (+/-14.2), and 123.6 (+/-14.4) mm Hg (P<0.001). During the follow-up, the mean systolic blood pressure increases in the 3 groups of paternal longevity were respectively 5.3 (+/-17.0), 4.2 (+/-14.0), and 1.6 (+/-13.2) mm Hg (P<0.001). In subjects without hypertension at baseline, hypertension occurred during the follow-up in 26.6%, 17.7%, and 15.3% (P<0.009), respectively. Multivariate analyses adjusted for baseline or changes in cardiovascular risk factors did not modify these results. In contrast, there was no relationship between maternal longevity and blood pressure measurements in either cross-sectional or longitudinal analyses. This study suggests that paternal premature death was associated with accelerated progression of systolic blood pressure and higher occurrence of hypertension in offspring. These results indicate that there are dynamic and continuous processes linking paternal longevity to blood pressure in adults.

Adult Children↗

Parental longevity and prognosis in elderly patients with aggressive non-Hodgkin's lymphoma.

In general, elderly patients with aggressive non-Hodgkin's lymphoma (NHL) have a less favourable prognosis than younger patients. Established predictors of prognosis in NHL are less discriminatory in the elderly, which is why there is a need for additional markers giving guidance on treatment decisions and prediction of outcome. The expected length of life of an individual in the general population is intimately associated with that of his/her parents. The aim of this study was to test the hypothesis that parental longevity is associated with improved outcome also among elderly patients with aggressive NHL and thus serves as an easily accessible non-disease associated prognostic factor. A total of 220 patients ( > 60 years) with aggressive NHL with a median age of 71 years (range 60-86) were included. Patients were randomized to receive CHOP or CNOP (doxorubicin replaced with mitoxantrone) chemotherapy with or without the addition of granulocyte colony-stimulating factor. The median follow-up time was 56 (19-89) months. Parental data regarding age at death were available through parish offices for 425 (97%) parents. Relative risk (RR) of death (disease-specific and all-cause) associated with parental lifespan was assessed using Cox proportional hazards regression analyses, with adjustment for sex, age, prognostic index, symptoms, and calendar period of diagnosis. Maternal lifespan below (versus above) median was associated with a borderline significant reduced disease-specific (adjusted RR of death from NHL = 1.5; 95% confidence interval 1.0-2.1) and overall survival. The effect of maternal lifespan was somewhat more pronounced in patients receiving CHOP than CNOP treatment. Paternal lifespan below the median was associated with a borderline significant increased disease-specific (adjusted RR of death from NHL = 0.8 [0.5-1.0]) and overall survival. Combined, maternal, and paternal lifespan had little impact on survival. These effects were true also when CHOP and CNOP treated patients were analysed separately. Maternal and paternal lifespan may predict survival in NHL, but with opposing effects. At present parental age appears not to be a clinically useful predictor of prognosis in the elderly with aggressive NHL.

Aged↗

[Effect of parental longevity and smoking on the pulmonary function in elderly persons].

The significance of smoking habits and long age of parents on lung function in a large population of elderly people (559 males and 1073 females) living in the city of Cracow were analyzed. The lung function parameters correlated negatively with age of analyzed subjects (males and females). Mean values of FVC in men from long living families were 400 ml higher in comparison with other subjects, while the mean FEV1 was 330 ml higher. Such differences were not seen in females. Smoking also affected negatively lung function in the analyzed subjects. Chronic cough and sputum production did not hamper lung function, if such variables as age, height and smoking habits were not included in the analysis.

Age Factors↗

Family history, longevity, and risk of coronary heart disease: the PRIME Study.

BACKGROUND: To assess the contribution of family history of coronary heart disease (CHD) and longevity in parents to 5-year incidence of coronary events in middle-aged men. METHODS: A prospective study in men from Northern Ireland and the French cities and environs of Lille, Strasbourg, and Toulouse. A total of 10 600 men aged 50-59 years were examined between 1991 and 1994 and followed annually by questionnaire for incident cases of coronary disease. A detailed family history was taken and a quantitative family risk score for CHD was calculated for each subject. Five-year follow-up is complete; all coronary events (coronary deaths, myocardial infarction, and angina) documented by clinical records were reviewed by an independent medical committee. RESULTS: At screening, 9758 subjects were free of clinical and historical evidence of CHD; in this group there were 317 coronary events by 5 years of follow-up. Subjects whose parents had both survived until >/=80 years showed a relative odds of 0.49 (95% CI: 0.31-0.77) for risk of a coronary event compared with subjects whose parents had not survived until >/=80 years old with adjustment for age and nine other risk factors including family history. The pattern of results was similar in France and Northern Ireland, although parental survival was longer in France. Likewise, subjects with a strong family history showed a relative odds of 1.93 (95% CI: 1.25-3.00) compared with subjects without such a history, after adjustment for age and the nine risk factors including parental longevity. The pattern of results was similar in France and Northern Ireland. CONCLUSIONS: These results indicate that a family history of coronary disease and parental longevity, although related, act independently of one another and of other major cardiovascular risk factors in predicting 5-year risk of subsequent coronary events.

Aged↗

Hypothesis on transmission of longevity based on telomere length and state of integrity.

Different studies have demonstrated that offspring longevity depends on parental longevity and parental age at conception. The present paper suggests, based on the telomere theory of aging, that the longevity of the offspring is proportional to the telomere length and inversely proportional to the telomere state of integrity in the sperm cell and oocyte at conception. These two characteristics of telomeres depend on the age of parents. Telomeres become longer in gametes during the course of life, but at the same time they accumulate mutations (reduced state of integrity) that cause a faster loss of repetitive sequences. Because of these two mechanisms with opposing effects, there could exist an ideal age of the parents for the transmission of maximal longevity. The different longevity of men and women could partly be the result of different telomere dynamics of the sex chromosomes. The hypothesis also explains the risk of some birth defects associated with parental age at birth (telomeres are taken as a cause of birth defects).

Aging↗

Effects of smoking and longevity of parents on lung function in the apparently healty elderly.

The assessment of the effects of smoking and longevity of parents on lung function in the elderly was carried out in a large sample of men (559) and women (1073) in Cracow. The lung function indices decreased linearly with age both in men and women. The mean levels of forced vital capacity (FVC) in the elderly males from long-lived parents were higher by about 400 ml and of forced expiratory volume in 1 sec (FEV1) were higher by 330 ml in comparison to subjects of shorter-lived parents. No similar differences in elderly women have been found. The data showed that active smoking affected lung function into advanced old age and that its effect was similar in both men and women. It was found that a history of chronic cough was not related to the impairment of lung function after inclusion of smoking status in the multiple regression models.

Journal Article↗

Determinants of high density lipoprotein and total cholesterol in women.

An epidemiological study was carried out among a random sample of women aged 18 to 69 years to examine possible determinants of plasma high density lipoprotein and total cholesterol (HDL-C and T-C). In a multiple regression analysis consumption of alcohol, fatty fish, and parental longevity showed positive associations with HDL-C, which were statistically significant. Smoking habit, sucrose consumption, and a family history of ischaemic heart disease showed significantly negative associations. In contrast, T-C was associated significantly only with age and Quetelet's index of body mass. Five variables having significant associations with HDL-C explained only 8% of the total variance; in the case of T-C 17% of the variance was explained by age and body mass.

Adolescent↗