Relationship between physical activity, sleep and aging: a Mendelian randomization study_West China Medical Journal

Authors：

LONG Lifang ¹ , WEI Lin ² , WANG Qiuting ² , XIE Jiaxin ³ , ZHU Xinxin ¹ , XIE Xiangqi ³ ,  LIN Meizhen ^1,2

1. School of Nursing, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P. R. China;
2. Nursing Department, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China;
3. The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China;

Corresponding?author：

LIN Meizhen, Email: lmzmay@163.com

Keywords：

Physical activity; sleep; aging; Mendelian randomization

DOI：

10.7507/1002-0179.202309067

Video：

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Objective To explore the correlation between physical activity, sleep and aging using a two-sample Mendelian randomization (MR) method. Methods The data through genome-wide association studies was summarized. The single nucleotide polymorphisms (SNPs) related to physical activity and sleep as instrumental variables was selected. The inverse variance weighting method was used for the main analyses, complemented by the weighted median method and MR Egger regression, and then sensitivity analyses were carried out in terms of multiplicity, heterogeneity and leave-one-out method. Finally, multivariate Mendelian methods were applied to eliminate confounders and find mediators. Results A total of two types of physical activity (strong physical activity, physical inactivity) and three sleep conditions (daytime naps, short sleep duration, adequate sleep duration) were found to have a causal relationship with frailty index (P<0.05), while physical inactivity was found to have a causal relationship with telomere length (P<0.05). A total of 167 SNPs were included in the analysis. Strong physical activity [correlation coefficient (β)=?1.26, 95% confidence interval (CI) (?1.60, ?0.96), P<0.0001], adequate sleep duration [β=?0.17, 95%CI (?0.26, ?0.09), P<0.001] were negatively correlated with the frailty index. Physical inactivity [β=1.47, 95%CI (0.85, 2.08), P<0.001], daytime naps [β=0.25, 95%CI (0.12, 0.39), P=0.0002], and short sleep duration [β=0.20, 95%CI (0.13, 0.27), P<0.0001] were positively associated with frailty index. Physical inactivity [β=?0.38, 95%CI (?0.69, ?0.07), P=0.02] was negatively correlated with telomere length. Percentage body fat, body fat mass, waist circumference, body weight and body mass index partially mediated 25.52%, 23.52%, 10.08%, 17.6% and 10.08% of the effect between daytime naps and frailty index, respectively. Conclusion There is a causal relationship between physical activity, sleep, and aging.

Citation： LONG Lifang, WEI Lin, WANG Qiuting, XIE Jiaxin, ZHU Xinxin, XIE Xiangqi, LIN Meizhen. Relationship between physical activity, sleep and aging: a Mendelian randomization study. West China Medical Journal, 2024, 39(5): 776-783. doi: 10.7507/1002-0179.202309067 Copy

1.	夏天吉, 閆明珠, 王智, 等. 大小鼠失眠模型和評價方法研究進展. 中國實驗動物學報, 2022, 30(3): 428-435.
2.	黃鑫, 李蘇寧, 尹軍祥, 等. 我國睡眠障礙防控研究現狀及建議. 四川大學學報(醫學版), 2023, 54(2): 226-230.
3.	林瑜. 我國體力活動研究現狀評述. 鄂州大學學報, 2019, 26(1): 103-104.
4.	榮璠, 萬宇輝. 體力活動影響衰老的研究進展. 現代預防醫學, 2022, 49(8): 1453-1456, 1461.
5.	Chen Z, Chen Z, Jin X. Mendelian randomization supports causality between overweight status and accelerated aging. Aging Cell, 2023, 22(8): e13899.
6.	潘賢麗, 蘇增鋒. 失眠與端粒長度和衰老的相關性研究進展. 中華全科醫學, 2023, 21(3): 481-484.
7.	和思敏, 張雨, 彭劉慶, 等. 傾向性評分與孟德爾隨機化國內研究現狀. 中華疾病控制雜志, 2022, 26(3): 325-330.
8.	于天琦, 徐文濤, 蘇雅娜, 等. 孟德爾隨機化研究基本原理、方法和局限性. 中國循證醫學雜志, 2021, 21(10): 1227-1234.
9.	Zhao G, Lu Z, Sun Y, et al. Dissecting the causal association between social or physical inactivity and depression: a bidirectional two-sample Mendelian randomization study. Transl Psychiatry, 2023, 13(1): 194.
10.	Dashti HS, Jones SE, Wood AR, et al. Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates. Nat Commun, 2019, 10(1): 1100.
11.	Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
12.	Curtin F, Schulz P. Multiple correlations and Bonferroni’s correction. Biol Psychiatry, 1998, 44(8): 775-777.
13.	Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol, 2016, 40(7): 597-608.
14.	Burgess S, Bowden J, Fall T, et al. Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants. Epidemiology, 2017, 28(1): 30-42.
15.	Burgess S, Thompson SG. Erratum to: interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol, 2017, 32(5): 391-392.
16.	Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in Mendelian randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol, 2016, 40(4): 304-314.
17.	Greco MFD, Minelli C, Sheehan NA, et al. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med, 2015, 34(21): 2926-2940.
18.	Yuan S, Levin MG, Titova OE, et al. Sleep duration, daytime napping, and risk of peripheral artery disease: multinational cohort and Mendelian randomization studies. Eur Heart J Open, 2023, 3(2): oead008.
19.	Li P, Gao L, Yu L, et al. Daytime napping and Alzheimer’s dementia: a potential bidirectional relationship. Alzheimers Dement, 2023, 19(1): 158-168.
20.	Wang X, Xu Y, Li X, et al. Day-to-day deviations in sleep parameters and biological aging: findings from the NHANES 2011-2014. Sleep Health, 2023, 9(6): 940-946.
21.	Mc Carthy CE, Yusuf S, Judge C, et al. Sleep patterns and the risk of acute stroke: results from the INTERSTROKE international case-control study. Neurology, 2023, 100(21): e2191-e2203.
22.	周妍欣, 趙丹, 王惜媛, 等. 農村慢性病老年人口腔健康與心理健康關系及睡眠質量的中介作用. 中國公共衛生, 2023, 39(4): 462-466.
23.	健康中國行動推進委員會. 健康中國行動(2019—2030 年): 總體要求、重大行動及主要指標. 中國循環雜志, 2019, 34(9): 846-858.
24.	馮佳, 王潔, 余丹, 等. 2010—2021 年國內外老年多重慢病研究熱點分析. 中國全科醫學, 2023, 26(21): 2574-2580.
25.	Boonpor J, Parra-soto S, Petermann-Rocha F, et al. Dose-response relationship between device-measured physical activity and incident type 2 diabetes: findings from the UK biobank prospective cohort study. BMC Med, 2023, 21(1): 191.
26.	Anderson E, Durstine JL. Physical activity, exercise, and chronic diseases: a brief review. Sports Med Health Sci, 2019, 1(1): 3-10.
27.	Ho FK, Zhou Z, Petermann-rocha F, et al. Association between device-measured physical activity and incident heart failure: a prospective cohort study of 94 739 UK biobank participants. Circulation, 2022, 146(12): 883-891.
28.	Lancet. Loneliness as a health issue. Lancet, 2023, 402(10396): 79.
29.	Pearce M, Garcia L, Abbas A, et al. Association between physical activity and risk of depression: a systematic review and meta-analysis. JAMA Psychiatry, 2022, 79(6): 550-559.
30.	Jepsen CH, Bowman-Busato J, Allvin T, et al. Achieving consensus on the language of obesity: a modified Delphi study. EClinicalMedicine, 2023, 62: 102061.
31.	Ma L, Chu M, Li Y, et al. Bidirectional relationships between weight stigma and pediatric obesity: a systematic review and meta-analysis. Obes Rev, 2021, 22(6): e13178.
32.	Masroor M, Haque Z. HbA_1C as a biomarker of non-alcoholic fatty liver disease: comparison with anthropometric parameters. J Clin Transl Hepatol, 2021, 9(1): 15-21.
33.	Fang H, Xie F, Li K, et al. Association between weight-adjusted-waist index and risk of cardiovascular diseases in United States adults: a cross-sectional study. BMC Cardiovasc Disord, 2023, 23(1): 435.
34.	Liu Y, Peng T, Zhang S, et al. The relationship between depression, daytime napping, daytime dysfunction, and snoring in 0. 5 million Chinese populations: exploring the effects of socio-economic status and age. BMC Public Health, 2018, 18(1): 759.
35.	Dashti HS, Daghlas I, Lane JM, et al. Genetic determinants of daytime napping and effects on cardiometabolic health. Nat Commun, 2021, 12(1): 900.

1. 夏天吉, 閆明珠, 王智, 等. 大小鼠失眠模型和評價方法研究進展. 中國實驗動物學報, 2022, 30(3): 428-435.
2. 黃鑫, 李蘇寧, 尹軍祥, 等. 我國睡眠障礙防控研究現狀及建議. 四川大學學報(醫學版), 2023, 54(2): 226-230.
3. 林瑜. 我國體力活動研究現狀評述. 鄂州大學學報, 2019, 26(1): 103-104.
4. 榮璠, 萬宇輝. 體力活動影響衰老的研究進展. 現代預防醫學, 2022, 49(8): 1453-1456, 1461.
5. Chen Z, Chen Z, Jin X. Mendelian randomization supports causality between overweight status and accelerated aging. Aging Cell, 2023, 22(8): e13899.
6. 潘賢麗, 蘇增鋒. 失眠與端粒長度和衰老的相關性研究進展. 中華全科醫學, 2023, 21(3): 481-484.
7. 和思敏, 張雨, 彭劉慶, 等. 傾向性評分與孟德爾隨機化國內研究現狀. 中華疾病控制雜志, 2022, 26(3): 325-330.
8. 于天琦, 徐文濤, 蘇雅娜, 等. 孟德爾隨機化研究基本原理、方法和局限性. 中國循證醫學雜志, 2021, 21(10): 1227-1234.
9. Zhao G, Lu Z, Sun Y, et al. Dissecting the causal association between social or physical inactivity and depression: a bidirectional two-sample Mendelian randomization study. Transl Psychiatry, 2023, 13(1): 194.
10. Dashti HS, Jones SE, Wood AR, et al. Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates. Nat Commun, 2019, 10(1): 1100.
11. Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
12. Curtin F, Schulz P. Multiple correlations and Bonferroni’s correction. Biol Psychiatry, 1998, 44(8): 775-777.
13. Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol, 2016, 40(7): 597-608.
14. Burgess S, Bowden J, Fall T, et al. Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants. Epidemiology, 2017, 28(1): 30-42.
15. Burgess S, Thompson SG. Erratum to: interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol, 2017, 32(5): 391-392.
16. Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in Mendelian randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol, 2016, 40(4): 304-314.
17. Greco MFD, Minelli C, Sheehan NA, et al. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med, 2015, 34(21): 2926-2940.
18. Yuan S, Levin MG, Titova OE, et al. Sleep duration, daytime napping, and risk of peripheral artery disease: multinational cohort and Mendelian randomization studies. Eur Heart J Open, 2023, 3(2): oead008.
19. Li P, Gao L, Yu L, et al. Daytime napping and Alzheimer’s dementia: a potential bidirectional relationship. Alzheimers Dement, 2023, 19(1): 158-168.
20. Wang X, Xu Y, Li X, et al. Day-to-day deviations in sleep parameters and biological aging: findings from the NHANES 2011-2014. Sleep Health, 2023, 9(6): 940-946.
21. Mc Carthy CE, Yusuf S, Judge C, et al. Sleep patterns and the risk of acute stroke: results from the INTERSTROKE international case-control study. Neurology, 2023, 100(21): e2191-e2203.
22. 周妍欣, 趙丹, 王惜媛, 等. 農村慢性病老年人口腔健康與心理健康關系及睡眠質量的中介作用. 中國公共衛生, 2023, 39(4): 462-466.
23. 健康中國行動推進委員會. 健康中國行動(2019—2030 年): 總體要求、重大行動及主要指標. 中國循環雜志, 2019, 34(9): 846-858.
24. 馮佳, 王潔, 余丹, 等. 2010—2021 年國內外老年多重慢病研究熱點分析. 中國全科醫學, 2023, 26(21): 2574-2580.
25. Boonpor J, Parra-soto S, Petermann-Rocha F, et al. Dose-response relationship between device-measured physical activity and incident type 2 diabetes: findings from the UK biobank prospective cohort study. BMC Med, 2023, 21(1): 191.
26. Anderson E, Durstine JL. Physical activity, exercise, and chronic diseases: a brief review. Sports Med Health Sci, 2019, 1(1): 3-10.
27. Ho FK, Zhou Z, Petermann-rocha F, et al. Association between device-measured physical activity and incident heart failure: a prospective cohort study of 94 739 UK biobank participants. Circulation, 2022, 146(12): 883-891.
28. Lancet. Loneliness as a health issue. Lancet, 2023, 402(10396): 79.
29. Pearce M, Garcia L, Abbas A, et al. Association between physical activity and risk of depression: a systematic review and meta-analysis. JAMA Psychiatry, 2022, 79(6): 550-559.
30. Jepsen CH, Bowman-Busato J, Allvin T, et al. Achieving consensus on the language of obesity: a modified Delphi study. EClinicalMedicine, 2023, 62: 102061.
31. Ma L, Chu M, Li Y, et al. Bidirectional relationships between weight stigma and pediatric obesity: a systematic review and meta-analysis. Obes Rev, 2021, 22(6): e13178.
32. Masroor M, Haque Z. HbA_1C as a biomarker of non-alcoholic fatty liver disease: comparison with anthropometric parameters. J Clin Transl Hepatol, 2021, 9(1): 15-21.
33. Fang H, Xie F, Li K, et al. Association between weight-adjusted-waist index and risk of cardiovascular diseases in United States adults: a cross-sectional study. BMC Cardiovasc Disord, 2023, 23(1): 435.
34. Liu Y, Peng T, Zhang S, et al. The relationship between depression, daytime napping, daytime dysfunction, and snoring in 0. 5 million Chinese populations: exploring the effects of socio-economic status and age. BMC Public Health, 2018, 18(1): 759.
35. Dashti HS, Daghlas I, Lane JM, et al. Genetic determinants of daytime napping and effects on cardiometabolic health. Nat Commun, 2021, 12(1): 900.

West China Medical Journal

Relationship between physical activity, sleep and aging: a Mendelian randomization study

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