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Mobility in old age turned out to be more important than longevity genes in women
Oleg Lischuk, N+1
American scientists have concluded that the level of physical activity and the total duration of sedentary pastime affect life expectancy more than genetic variants associated with longevity. The study involving almost 5.5 thousand elderly women lasted more than six years. A report on it is published in the Journal of Aging and Physical Activity (Posis et al., Associations of Accelerometer-Measured Physical Activity and Sedentary Time With All-Cause Mortality by Genetic Predisposition for Longevity).
Both heredity and environmental factors, including lifestyle, affect life expectancy. On the one hand, thanks to genome-wide association searches (GWAS), a whole set of single-nucleotide polymorphisms (SNPs) associated with longevity is currently known. On the other hand, meta—analyses have shown that moderate and high intensity physical activity in old age significantly reduces mortality, and the lack of mobility measured by an accelerometer increases it. At the same time, the question of the mutual influence of genetic factors and physical activity remained open.
To answer it, the staff of the University of California at San Diego with colleagues from other American research centers under the leadership of Aladdin Shadyab analyzed data from a large-scale multicenter prospective study OPACH (Objective Physical Activity and Cardiovascular Health, an objective assessment of physical activity and cardiovascular health). The final sample included 5,446 women aged 63 years and older, who were included in the work from March 2012 to April 2014 and continued observation until the end of February 2020. The average follow-up time for each participant was 6.1 years.
To assess physical activity and the duration of sedentary pastime, all women wore a high-precision three-axis accelerometer on their right hip around the clock during the week (with the exception of bathing and swimming), and also recorded the time of waking up and going to bed. The researchers identified the periods of removal of the device using the validating Choi algorithm. The removed indicators were divided into 15-second fragments for ease of processing. The level of physical activity was calculated by the sum of the readings of the length of the accelerometer vectors for one such fragment. 18 or less counts in 15 seconds were taken as a sedentary pastime corresponding to less than 1.6 metabolic equivalents (MET; one corresponds to the energy consumed by a person in a sitting position in a state of complete rest). 19-518 counts in 15 seconds were taken as low intensity loads (1.6–2.9 MET); 519 or more counts in 15 seconds — moderate and high intensity (3.0 or more MET).
Hereditary predisposition to longevity was judged by three SNPs, for which high significance was shown in the meta—analysis of 18 GWAS and the effect size was calculated - rs429358, rs7412 and rs7676745. The first two relate to the APOE gene, the third to the intron of the GPR78 gene. According to the number of corresponding alleles and the size of their effect, weighted indicators of genetic risk were calculated and divided into terciles (low, medium and high predisposition to longevity).
The amendments were introduced for age, ethnicity, education, body mass index, subjective assessment of health, physical functionality according to the RAND-36 questionnaire, alcohol consumption, tobacco smoking and concomitant chronic diseases. The final analysis of continuous variables was carried out using the Kraskel—Wallis criterion, discrete variables — the Pearson consensus criterion, and the correlation of physical activity level with mortality — the Cox regression.
A total of 1,022 deaths occurred over 33,350 person-years of follow-up; in the groups with high (36 percent of participants), medium (33.1 percent) and low (30.9 percent) predisposition to longevity, there were 295, 381 and 346, respectively. At the same time, women from the latter group as a whole turned out to be younger, more physically functional and mobile compared to the first two.
The level of physical activity was inversely associated with mortality, inactivity — directly. Compared with the lowest quartile of low—intensity loads, the risk ratio (HR) in three quartiles was 0.72; 0.70 and 0.55 in ascending order; moderate and high intensity — 0.76; 0.60 and 0.46; total duration of sedentary pastime - 1.22; 1.69 and 2.05, respectively.
After stratification by predisposition to longevity, this pattern persisted. At the same time, without taking into account the deaths that occurred during the first two years of observations, HR for the relationship of physical exertion and inactivity with mortality decreased slightly regardless of genetic variants. The mutual influence of physical activity and APOE ϵ2 or ϵ4 genotypes turned out to be statistically insignificant.
Thus, even with unfavorable heredity, it is possible to significantly extend the years of life if you move more and sit less, and vice versa, a sedentary lifestyle may not allow a predisposition to longevity to be realized, concluded Shadyab. The authors note that since they used data from a study in which only women participated, it is necessary to study men in the future in order to understand how the results obtained are valid for both sexes.
Previous studies have shown that physical exercise can offset the increased risk of death due to inactivity, preserve cognitive abilities in neurodegenerative diseases, protect muscles from dystrophy during inflammation, and even increase the level of antibodies after flu and covid vaccinations.
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