ABSTRACT Short sleep duration has a substantial influence on the overall health of an individual. Short sleep time can be a consequence of lifestyle habits, environmental factors, or the

presence of a sleep disorder, such as insomnia or sleep-disordered breathing. Short sleep time is associated with increased morbidity and mortality, mainly from cardiovascular disorders

(including coronary artery disease, arrhythmias, and hypertension). Several biological mechanisms have been proposed as a possible link between short sleep duration and these diseases, such

as involvement of the autonomic nervous system, endothelial function, metabolic regulation, inflammation, and the coagulation system. In this Review, we provide an overview on the effects of

important alterations in several intermediate biological mechanisms, such as the autonomic nervous system, endothelial function, insulin and glucose regulation, inflammation, and

coagulation. * Although a causal relationship between short sleep duration and cardiovascular risk is not confirmed, most of the data indicate a strong link between short sleep times and

diabetes mellitus, obesity, and cardiovascular disorders. * Physicians should consider sleep to be a modifiable risk factor for health status, with particular relevance to cardiovascular and

metabolic disorders. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution

Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $29.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12

print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be

subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR

CONTENT BEING VIEWED BY OTHERS SLEEP DISTURBANCES: ONE OF THE CULPRITS OF OBESITY-RELATED CARDIOVASCULAR RISK? Article 20 July 2020 THE ASSOCIATION BETWEEN SLEEP DURATION AND HYPERTENSION: A

META AND STUDY SEQUENTIAL ANALYSIS Article 25 June 2020 INFLUENCE OF SLEEP ON PHYSIOLOGICAL SYSTEMS IN ATHEROSCLEROSIS Article 08 November 2024 REFERENCES * Watson, N. et al. Recommended

amount of sleep for a healthy adult: a joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. _J. Clin. Sleep Med._ 11, 931–952 (2015). Article 

PubMed  PubMed Central  Google Scholar  * Hirshkowitz, M. et al. National Sleep Foundation’s updated sleep duration recommendations: final report. _Sleep Heal._ 1, 233–243 (2015). Article 

Google Scholar  * Liu, Y. et al. Prevalence of healthy sleep duration among adults — United States, 2014. _MMWR Morb. Mortal. Wkly Rep._ 65, 137–141 (2016). Article  PubMed  Google Scholar 

* Grandner, M. A., Patel, N. P., Gehrman, P. R., Perlis, M. L. & Pack, A. I. Problems associated with short sleep: bridging the gap between laboratory and epidemiological studies. _Sleep

Med. Rev._ 14, 239–247 (2010). Article  PubMed  Google Scholar  * Wheaton, A. G., Jones, S. E., Cooper, A. C. & Croft, J. B. Short sleep duration among middle school and high school

students — United States, 2015. _MMWR Morb. Mortal. Wkly Rep._ 67, 85–90 (2018). Article  PubMed  PubMed Central  Google Scholar  * Schutte-rodin, S. et al. Clinical guideline for the

evaluation and management of chronic insomnia in adults. _J. Clin. Sleep Med._ 4, 487–504 (2008). PubMed  PubMed Central  Google Scholar  * Young, T. et al. The occurrence of

sleep-disordered breathing among middle-aged adults. _N. Engl. J. Med._ 328, 1230–1235 (1993). Article  CAS  PubMed  Google Scholar  * Peppard, P. E. et al. Increased prevalence of

sleep-disordered breathing in adults. _Am. J. Epidemiol._ 177, 1006–1014 (2013). Article  PubMed  PubMed Central  Google Scholar  * Heinzer, R. et al. Prevalence of sleep-disordered

breathing in the general population: the HypnoLaus study. _Lancet Respir. Med._ 3, 310–318 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Chin, K. et al. Associations

between obstructive sleep apnea, metabolic syndrome, and sleep duration, as measured with an actigraph, in an urban male working population in Japan. _Sleep_ 33, 89–95 (2010). Article 

PubMed  PubMed Central  Google Scholar  * Vgontzas, A. N. et al. Insomnia with short sleep duration and mortality: the Penn State cohort. _Hypertension_ 33, 1159–1164 (2010). Google Scholar

  * Vgontzas, A. N., Fernandez-Mendoza, J., Liao, D. & Bixler, E. O. Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. _Sleep Med.

Rev._ 17, 241–254 (2013). Article  PubMed  PubMed Central  Google Scholar  * Ren, R. et al. Objective but not subjective short sleep duration is associated with hypertension in obstructive

sleep apnea. _Hypertension_ 72, 610–617 (2018). Article  CAS  Google Scholar  * Priou, P. et al. Cumulative association of obstructive sleep apnea severity and short sleep duration with the

risk for hypertension. _PLOS ONE_ 9, 1–12 (2014). Article  CAS  Google Scholar  * Tobaldini, E. et al. Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases.

_Neurosci. Biobehav. Rev._ 74, 321–329 (2017). Article  PubMed  Google Scholar  * Li, X. et al. U-shaped relationships between sleep duration and metabolic syndrome and metabolic syndrome

components in males: a prospective cohort study. _Sleep Med._ 16, 949–954 (2015). Article  PubMed  Google Scholar  * Kim, J. Y. et al. A prospective study of total sleep duration and

incident metabolic syndrome: the ARIRANG study. _Sleep Med._ 16, 1511–1515 (2015). Article  PubMed  Google Scholar  * Gottlieb, D. J. et al. Association of sleep time with diabetes mellitus

and impaired glucose tolerance. _Arch. Intern. Med._ 165, 863–867 (2005). Article  PubMed  Google Scholar  * Wu, Y., Zhai, L. & Zhang, D. Sleep duration and obesity among adults: a

meta-analysis of prospective studies. _Sleep Med._ 15, 1456–1462 (2014). Article  PubMed  Google Scholar  * Sabanayagam, C. & Shankar, A. Sleep duration and cardiovascular disease:

results from the National Health Interview Survey. _Sleep_ 33, 1037–1042 (2010). Article  PubMed  PubMed Central  Google Scholar  * Sauvet, F. et al. Effect of acute sleep deprivation on

vascular function in healthy subjects. _J. Appl. Physiol._ 108, 68–75 (2010). Article  PubMed  Google Scholar  * Tobaldini, E. et al. One night on-call: sleep deprivation affects cardiac

autonomic control and inflammation in physicians. _Eur. J. Intern. Med._ 24, 664–670 (2013). Article  PubMed  Google Scholar  * Zhong, X. et al. Increased sympathetic and decreased

parasympathetic cardiovascular modulation in normal humans with acute sleep deprivation. _J. Appl. Physiol._ 98, 2024–2032 (2005). Article  PubMed  Google Scholar  * Dettoni, J. L. et al.

Cardiovascular effects of partial sleep deprivation in healthy volunteers. _J. Appl. Physiol._ 113, 232–236 (2012). Article  CAS  PubMed  Google Scholar  * Takase, B. et al. Effects of

chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels. _Biomed. Pharmacother._ 58, 35–39 (2004).

Article  Google Scholar  * Grimaldi, D., Carter, J. R., Van Cauter, E. & Leproult, R. Adverse impact of sleep restriction and circadian misalignment on autonomic function in healthy

young adults. _Hypertension_ 68, 243–250 (2016). Article  CAS  PubMed  Google Scholar  * Spiegel, K., Leproult, R. & Van Cauter, E. Impact of sleep debt on metabolic and endocrine

function. _Lancet_ 354, 1435–1439 (1999). Article  CAS  PubMed  Google Scholar  * Neufeld, E. V., Carney, J. J., Dolezal, B. A., Boland, D. M. & Cooper, C. B. Exploratory study of heart

rate variability and sleep among emergency medical services shift workers. _Prehospital Emerg_. _Care_ 21, 18–23 (2017). Google Scholar  * Chung, M. et al. Recovery after three-shift work:

relation to sleep-related cardiac neuronal regulation in nurses. _Ind. Health_ 1, 24–30 (2012). Article  Google Scholar  * Su, T. C. et al. Elevated blood pressure, decreased heart rate

variability and incomplete blood pressure recovery after a 12-hour night shift work. _J. Occup. Health_ 50, 380–386 (2008). Article  PubMed  Google Scholar  * Yamasaki, F., Schwartz, J. E.,

Gerber, L. M., Warren, K. & Pickering, T. G. Impact of shift work and race/ethnicity on the diurnal rhythm of blood pressure and catecholamines. _Hypertension_ 32, 417–423 (1998).

Article  CAS  PubMed  Google Scholar  * Irwin, M. R. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. _Arch. Intern. Med._ 166, 1756

(2006). Article  CAS  PubMed  Google Scholar  * Irwin, M. R., Witarama, T., Caudill, M., Olmstead, R. & Breen, E. C. Sleep loss activates cellular inflammation and signal transducer and

activator of transcription (STAT) family proteins in humans. _Brain. Behav. Immun._ 47, 86–92 (2015). Article  CAS  PubMed  Google Scholar  * Sauvet, F. et al. Vascular response to 1 week of

sleep restriction in healthy subjects. A metabolic response? _Int. J. Cardiol._ 190, 246–255 (2015). Article  PubMed  Google Scholar  * Vgontzas, A. N. et al. Circadian interleukin-6

secretion and quantity and depth of sleep. _J. Clin. Endocrinol. Metab._ 84, 2603–2607 (1999). Article  CAS  PubMed  Google Scholar  * Meier-Ewert, H. K. et al. Effect of sleep loss on

C-Reactive protein, an inflammatory marker of cardiovascular risk. _J. Am. Coll. Cardiol._ 43, 678–683 (2004). Article  CAS  PubMed  Google Scholar  * van Leeuwen, W. M. A. et al. Sleep

restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. _PLOS ONE_ 4, e4589 (2009). Article  PubMed  PubMed

Central  CAS  Google Scholar  * Ferrie, J. E. et al. Associations between change in sleep duration and inflammation: findings on C-reactive protein and interleukin 6 in the Whitehall II

study. _Am. J. Epidemiol._ 178, 956–961 (2013). Article  PubMed  PubMed Central  Google Scholar  * Miller, M. a et al. Gender differences in the cross-sectional relationships between sleep

duration and markers of inflammation: Whitehall II study. _Sleep_ 32, 857–864 (2009). PubMed  PubMed Central  Google Scholar  * Faraut, B., Boudjeltia, K. Z., Vanhamme, L. & Kerkhofs, M.

Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery. _Sleep Med. Rev._ 16, 137–149 (2012). Article  PubMed  Google Scholar  * Boudjeltia, K. et al.

Temporal dissociation between myeloperoxidase (MPO)-modified LDL and MPO elevations during chronic sleep restriction and recovery in healthy young men. _PLOS ONE_ 6, e28230 (2011). Article 

PubMed  CAS  Google Scholar  * Weil, B. R. et al. Short sleep duration is associated with enhanced endothelin-1 vasoconstrictor tone. _Can. J. Physiol. Pharmacol._ 88, 777–781 (2010).

Article  CAS  PubMed  Google Scholar  * Nakazaki, C. et al. Association of insomnia and short sleep duration with atherosclerosis risk in the elderly. _Am. J. Hypertens._ 25, 1149–1155

(2012). Article  PubMed  Google Scholar  * Matthews, K. A., Dahl, R. E., Owens, J. F., Lee, L. & Hall, M. Sleep duration and insulin resistance in healthy black and white adolescents.

_Sleep_ 35, 1353–1358 (2012). Article  PubMed  PubMed Central  Google Scholar  * Rodrigues, De. Bernardi A. M. et al. Association of sleep deprivation with reduction in insulin sensitivity

as assessed by the hyperglycemic clamp technique in adolescents. _JAMA Pediatr._ 170, 487–494 (2016). Article  Google Scholar  * Reynolds, A. C. et al. Impact of five nights of sleep

restriction on glucose metabolism, leptin and testosterone in young adult men. _PLOS ONE_ 7, e41218 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * Donga, E. et al. Partial

sleep restriction decreases insulin sensitivity in type 1 diabetes. _Diabetes Care_ 33, 1573–1577 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Francesco, T., Peverini, F.,

De Benedetto, M. & De Nuccio, F. Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis. _Lung_ 191, 1–7 (2013). Article  CAS 

Google Scholar  * Robinson, G. V., Pepperell, J. C. T., Segal, H. C., Davies, R. J. O. & Stradling, J. R. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from

randomised controlled trials. _Thorax_ 59, 777–783 (2004). Article  CAS  PubMed  PubMed Central  Google Scholar  * Kondo, Y. et al. Significant relationship between platelet activation and

apnea-hypopnea index in patients with obstructive sleep apnea syndrome. _Tokai J. Exp. Clin. Med._ 36, 79–83 (2011). PubMed  Google Scholar  * Von Känel, R. et al. Association between

polysomnographic measures of disrupted sleep and prothrombotic factors. _Chest_ 131, 733–739 (2007). Article  Google Scholar  * Libby, P. Inflammation and cardiovascular disease mechanisms.

_Am. J. Clin. Nutr._ 83, 456–460 (2006). Article  Google Scholar  * Visser, M., Bouter, L. M., Mcquillan, G. M., Wener, M. H. & Harris, T. B. Elevated C-reactive protein levels in

overweight and obese adults. _JAMA_ 282, 2131–2135 (1999). Article  CAS  PubMed  Google Scholar  * Danesh, J. et al. Fibrin D-dimer and coronary heart disease prospective study and

meta-analysis. _Circulation_ 103, 2323–2327 (2001). Article  CAS  PubMed  Google Scholar  * Kim, H. C. et al. Multimarker prediction of coronary heart disease risk. _J. Am. Coll. Cardiol._

55, 2080–2091 (2010). Article  CAS  PubMed  Google Scholar  * Münzel, T. et al. Impact of oxidative stress on the heart and vasculature: Part 2 of a 3-Part series. _J. Am. Coll. Cardiol._

70, 212–229 (2017). Article  PubMed  PubMed Central  CAS  Google Scholar  * Itani, O., Jike, M., Watanabe, N. & Kaneita, Y. Short sleep duration and health outcomes: a systematic review,

meta-analysis, and meta-regression. _Sleep Med._ 32, 246–256 (2017). Article  PubMed  Google Scholar  * Chien, K.-L. et al. Habitual sleep duration and insomnia and the risk of

cardiovascular events and all-cause death: report from a community-based cohort. _Sleep_ 33, 177–184 (2010). Article  PubMed  PubMed Central  Google Scholar  * Campanini, M. Z. et al.

Agreement between sleep diary and actigraphy in a highly educated Brazilian population. _Sleep Med._ 35, 27–34 (2017). Article  PubMed  Google Scholar  * Lockley, S. W., Skene, D. J. &

Arendt, J. Comparison between subjective and actigraphic measurement of sleep and sleep rhythms. _J. Sleep Res._ 8, 175–183 (1999). Article  CAS  PubMed  Google Scholar  * Arora, T.,

Broglia, E., Pushpakumar, D., Lodhi, T. & Taheri, S. An investigation into the strength of the association and agreement levels between subjective and objective sleep duration in

adolescents. _PLOS ONE_ 8, 1–6 (2013). Google Scholar  * Girschik, J., Fritschi, L., Heyworth, J. & Waters, F. Validation of self-reported sleep against actigraphy. _J. Epidemiol._ 22,

462–468 (2012). Article  PubMed  PubMed Central  Google Scholar  * Ross, R. Atherosclerosis — An inflammatory disease. _N. Engl. J. Med._ 340, 115–126 (1999). Article  CAS  PubMed  Google

Scholar  * Willerson, J. T. Inflammation as a cardiovascular risk factor. _Circulation_ 109, II2–10 (2004). PubMed  Google Scholar  * Vgontzas, A. N. et al. Adverse effects of modest sleep

restriction on sleepiness, performance, and inflammatory cytokines. _J. Clin. Endocrinol. Metab._ 89, 2119–2126 (2004). Article  CAS  PubMed  Google Scholar  * Orshal, J. M. & Khalil, R.

a. Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats. _Am. J. Physiol. Regul. Integr. Comp. Physiol_.

286, R1013–R1023 (2004). Article  CAS  PubMed  Google Scholar  * Gangwisch, J. E. et al. Short sleep duration as a risk factor for hypertension: analyses of the first National Health and

Nutrition Examination survey. _Hypertension_ 47, 833–839 (2006). Article  CAS  PubMed  Google Scholar  * Cappuccio, F. P. et al. Gender-specific associations of short sleep duration with the

Whitehall II study. _Hypertension_ 50, 693–700 (2007). Article  CAS  PubMed  Google Scholar  * Knutson, K. L. et al. Association between sleep and blood pressure in midlife. _Arch. Intern.

Med._ 169, 1055 (2009). Article  PubMed  PubMed Central  Google Scholar  * Ridker, P. M. C-reactive protein and the prediction of cardiovascular events among those at intermediate risk

moving an inflammatory hypothesis toward consensus. _J. Am. Coll. Cardiol._ 49, 2129–2138 (2007). Article  CAS  PubMed  Google Scholar  * Albert, C. M., Ma, J., Rifai, N., Stampfer, M. J.

& Ridker, P. M. Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. _Circulation_ 105, 2595–2599 (2002). Article  CAS 

PubMed  Google Scholar  * Danesh, J. et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. _N. Engl. J. Med._ 350, 1387–1397

(2004). Article  CAS  PubMed  Google Scholar  * Calvin, A. D. et al. Experimental sleep restriction causes endothelial dysfunction in healthy humans. _J. Am. Heart Assoc._ 3, 1–7 (2014).

Article  Google Scholar  * Pongratz, G. & Straub, R. H. The sympathetic nervous response in inflammation. _Arthritis Res. Ther._ 16, 1–12 (2014). Article  CAS  Google Scholar  * Podrez,

E. A., Schmitt, D., Hoff, H. F. & Hazen, S. L. Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro. _J. Clin. Invest._ 103, 1547–1560

(1999). Article  CAS  PubMed  PubMed Central  Google Scholar  * van Leeuwen, W. M. A. et al. Prolonged sleep restriction affects glucose metabolism in healthy young men. _Int. J.

Endocrinol._ 2010, 108641 (2010). PubMed  PubMed Central  Google Scholar  * Paneni, F., Diaz Cañestro, C., Libby, P., Lüscher, T. F. & Camici, G. G. The aging cardiovascular system:

understanding it at the cellular and clinical levels. _J. Am. Coll. Cardiol._ 69, 1952–1967 (2017). Article  PubMed  Google Scholar  * Miller, M. A., Kandala, N., Kumari, M., Marmot, M. G.

& Cappuccio, F. P. Clinical and population studies relationships between sleep duration and von Willebrand factor, factor vii, and fibrinogen Whitehall II study. _Arter. Thromb. Vasc.

Biol._ 30, 2032–2039 (2010). Article  CAS  Google Scholar  * Tosur, Z. et al. The association between sleep characteristics and prothrombotic markers in a population based sample: Chicago

area sleep study. _Sleep Med._ 15, 973–978 (2014). Article  PubMed  PubMed Central  Google Scholar  * Chouchou, F. et al. Sympathetic overactivity due to sleep fragmentation is associated

with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study. _Eur. Heart J._ 34, 2122–2131 (2013). Article  CAS  PubMed  Google Scholar  * Muenter, N.

K. et al. Effect of sleep restriction on orthostatic cardiovascular control in humans. _J. Appl. Physiol._ 88, 966–972 (2000). Article  CAS  PubMed  Google Scholar  * Sforza, E. et al. Heart

rate activation during spontaneous arousals from sleep: effect of sleep deprivation. _Clin. Neurophysiol._ 115, 2442–2451 (2004). Article  PubMed  Google Scholar  * Malliani, A. &

Montano, N. Emerging excitatory role of cardiovascular sympathetic afferents in pathophysiological conditions. _Hypertension_ 39, 63–68 (2002). Article  CAS  PubMed  Google Scholar  * Shen,

M. J. & Zipes, D. P. Role of the autonomic nervous system in modulating cardiac arrhythmias. _Circ. Res._ 114, 1004–1021 (2014). Article  CAS  PubMed  Google Scholar  * Agarwal, S. K. et

al. Cardiac autonomic dysfunction and incidence of atrial fibrillation in a large population-based cohort. _J. Am. Coll. Cardiol._ 69, 291–299 (2017). Article  PubMed  PubMed Central 

Google Scholar  * Meredith, I. T., Broughton, A., Jennings, G. L. & Esler, M. D. Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular

arrhythmias. _N. Engl. J. Med._ 325, 618–624 (1991). Article  CAS  PubMed  Google Scholar  * Mancia, G. & Grassi, G. The autonomic nervous system and hypertension. _Circ. Res._ 114,

1804–1814 (2014). Article  CAS  PubMed  Google Scholar  * Airaksinen, K. E., Ikaheimo, M. J., Linnaluoto, M. K., Niemela, M. & Takkunen, J. T. Impaired vagal heart rate control in

coronary artery disease. _Heart_ 58, 592–597 (1987). Article  CAS  Google Scholar  * Kochiadakis, G. E. et al. Autonomic nervous system activity before and during episodes of myocardial

ischemia in patients with stable coronary artery disease during daily life. _Pacing Clin. Electrophysiol._ 23, 2030–2039 (2000). Article  CAS  PubMed  Google Scholar  * Huikuri, H. V. et al.

Heart rate variability and progression of coronary atherosclerosis. _Arter. Thromb. Vasc. Biol._ 19, 1979–1985 (1999). Article  CAS  Google Scholar  * van Bilsen, M. et al. The autonomic

nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of

Cardiology. _Eur. J. Hear. Fail._ 19, 1361–1378 (2017). Article  Google Scholar  * Floras, J. S. & Ponikowski, P. The sympathetic/parasympathetic imbalance in heart failure with reduced

ejection fraction. _Eur. Heart J._ 36, 1974–1982 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Wang, Y. et al. Chronic sleep fragmentation promotes obesity in young adult

mice. _Obesity_ 22, 758–762 (2014). Article  CAS  PubMed  Google Scholar  * Tracey, K. J. The inflammatory reflex. _Nature_ 420, 853–859 (2002). Article  CAS  PubMed  Google Scholar  *

Itani, O., Kaneita, Y., Murata, A., Yokoyama, E. & Ohida, T. Association of onset of obesity with sleep duration and shift work among Japanese adults. _Sleep Med._ 12, 341–345 (2011).

Article  PubMed  Google Scholar  * Cassidy, S., Chau, J. Y., Catt, M., Bauman, A. & Trenell, M. I. Cross-sectional study of diet, physical activity, television viewing and sleep duration

in 233 110 adults from the UK Biobank; the behavioural phenotype of cardiovascular disease and type 2 diabetes. _BMJ Open_ 6, e010038 (2016). Article  PubMed  PubMed Central  Google Scholar

  * Venancio, D. P. & Suchecki, D. Prolonged REM sleep restriction induces metabolic syndrome-related changes: mediation by pro-inflammatory cytokines. _Brain Behav. Immun._ 47, 109–117

(2015). Article  CAS  PubMed  Google Scholar  * Moraes, D. A., Venancio, D. P. & Suchecki, D. Sleep deprivation alters energy homeostasis through non-compensatory alterations in

hypothalamic insulin receptors in Wistar rats. _Horm. Behav._ 66, 705–712 (2014). Article  CAS  PubMed  Google Scholar  * Zhan, S. et al. Decrease in circulating fatty acids is associated

with islet dysfunction in chronically sleep-restricted rats. _Int. J. Mol. Sci._ 17, 2102 (2016). Article  PubMed Central  CAS  Google Scholar  * Jha, P. K., Foppen, E., Kalsbeek, A. &

Challet, E. Sleep restriction acutely impairs glucose tolerance in rats. _Physiol_. _Rep._ 4, e12839 (2016). Google Scholar  * Spiegel, K., Tasali, E., Penev, P. & Van Cauter, E. Brief

communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. _Ann. Intern. Med._ 141, 846–850

(2004). Article  PubMed  Google Scholar  * Broussard, J. L. et al. Insulin access to skeletal muscle is impaired during the early stages of diet-induced obesity. _Obesity_ 24, 1922–1928

(2016). Article  CAS  PubMed  Google Scholar  * Chapman, C. D. et al. Acute sleep deprivation increases food purchasing in men. _Obesity_ 21, E555–E560 (2013). Article  CAS  PubMed  Google

Scholar  * St-Onge, M.-P., O’Keeffe, M., Roberts, A. L., RoyChoudhury, A. & Laferrere, B. Short sleep duration, glucose dysregulation and hormonal regulation of appetite in men and

women. _Sleep_ 35, 1503–1510 (2012). Article  PubMed  PubMed Central  Google Scholar  * Markwald, R. R. et al. Impact of insufficient sleep on total daily energy expenditure, food intake,

and weight gain. _Proc. Natl Acad. Sci. USA_ 110, 5695–5700 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * de Oliveira, E. M. et al. Serum amyloid A production is triggered

by sleep deprivation in mice and humans: is that the link between sleep loss and associated comorbidities? _Nutrients_ 9, E311 (2017). Article  PubMed  CAS  Google Scholar  * DePorter, D.

P., Coborn, J. E. & Teske, J. A. Partial sleep deprivation reduces the efficacy of orexin-A to stimulate physical activity and energy expenditure. _Obesity_ 25, 1716–1722 (2017). Article

  CAS  PubMed  Google Scholar  * Parrish, J. B. & Teske, J. A. Acute partial sleep deprivation due to environmental noise increases weight gain by reducing energy expenditure in rodents.

_Obesity_ 25, 141–146 (2017). Article  PubMed  Google Scholar  * de Oliveira, E. M. et al. Late effects of sleep restriction: potentiating weight gain and insulin resistance arising from a

high-fat diet in mice. _Obesity_ 23, 391–398 (2015). Article  PubMed  CAS  Google Scholar  * Zhang, S. X. L. et al. Sleep fragmentation promotes NADPH oxidase 2-mediated adipose tissue

inflammation leading to insulin resistance in mice. _Int. J. Obes._ 38, 619–624 (2014). Article  CAS  Google Scholar  * Weyer, C. et al. Hypoadiponectinemia in obesity and type 2 diabetes:

close association with insulin resistance and hyperinsulinemia. _J. Clin. Endocrinol. Metab._ 86, 1930–1935 (2001). Article  CAS  PubMed  Google Scholar  * Yamauchi, T. et al. The

fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. _Nat. Med._ 7, 941–946 (2001). Article  CAS  PubMed  Google Scholar  * Simpson, N.

S., Banks, S., Arroyo, S. & Dinges, D. F. Effects of sleep restriction on adiponectin levels in healthy men and women. _Physiol. Rep._ 101, 693–698 (2010). CAS  Google Scholar  *

Nilsson, P. M., Rööst, M., Engström, G., Hedblad, B. & Berglund, G. Incidence of diabetes in middle-aged men is related to sleep disturbances. _Diabetes Care_ 27, 2464–2469 (2004).

Article  PubMed  Google Scholar  * Tasali, E., Leproult, R., Ehrmann, D. A. & Van Cauter, E. Slow-wave sleep and the risk of type 2 diabetes in humans. _Proc. Natl Acad. Sci. USA_ 105,

1044–1049 (2008). Article  CAS  PubMed  PubMed Central  Google Scholar  * Benedict, C., Barclay, J. L., Ott, V., Oster, H. & Hallschmid, M. Acute sleep deprivation delays the

glucagon-like peptide 1 peak response to breakfast in healthy men. _Nutr. Diabetes_ 3, e78 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Aho, V. et al. Prolonged sleep

restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses. _Sci. Rep._ 6, 24828 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  *

O’Keeffe, M., Roberts, A. L., Kelleman, M., RoyChoudhury, A. & St-Onge, M.-P. No effects of short-term sleep restriction, in a controlled feeding setting, on lipid profiles in normal

weight adults. _J. Sleep Res_. 22 (2013). * Skuladottir, G. V., Nilsson, E. K., Mwinyi, J. & Schioth, H. B. One-night sleep deprivation induces changes in the DNA methylation and serum

activity indices of stearoyl-CoA desaturase in young healthy men. _Lipids Health Dis._ 15, 137 (2016). Article  PubMed  PubMed Central  CAS  Google Scholar  * Broussard, J. L. et al. Sleep

restriction increases free fatty acids in healthy men. _Diabetologia_ 58, 791–798 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Riggs, D. W., Yeager, R. A. & Bhatnagar,

A. An omics approach for assessing the environmental risk of cardiovascular disease. _Circ. Res._ 122, 1259–1275 (2018). Article  CAS  PubMed  PubMed Central  Google Scholar  * Cappuccio,

F. P., Cooper, D., D.’Elia, L., Strazzullo, P. & Miller, M. A. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. _Eur. Heart

J_. 32, 1484–1492 (2011). Article  PubMed  Google Scholar  * Ikehara, S. et al. Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and

women: the JACC study. _Sleep_ 32, 295–301 (2009). Article  PubMed  PubMed Central  Google Scholar  * Pepin, J. L. et al. Hypertension and sleep: overview of a tight relationship. _Sleep

Med. Rev._ 18, 509–519 (2014). Article  PubMed  Google Scholar  * Gottlieb, D. J. et al. Association of usual sleep duration with hypertension: the Sleep Heart Health Study. _Sleep_ 29,

1009–1014 (2006). Article  PubMed  Google Scholar  * Guo, X. et al. Epidemiological evidence for the link between sleep duration and high blood pressure: a systematic review and

meta-analysis. _Sleep Med._ 14, 324–332 (2013). Article  PubMed  Google Scholar  * Wang, Q., Xi, B., Liu, M., Zhang, Y. & Fu, M. Short sleep duration is associated with hypertension risk

among adults: a systematic review and meta-analysis. _Hypertens. Res._ 35, 1012–1018 (2012). Article  PubMed  Google Scholar  * Wang, Y. et al. Relationship between duration of sleep and

hypertension in adults: a meta-analysis. _J. Clin. Sleep Med._ 11, 1047–1056 (2015). PubMed  PubMed Central  Google Scholar  * Meng, L., Zheng, Y. & Hui, R. The relationship of sleep

duration and insomnia to risk of hypertension incidence: a meta-analysis of prospective cohort studies. _Hypertens. Res._ 36, 985–995 (2013). Article  PubMed  PubMed Central  Google Scholar

  * Wu, X. et al. Association of self-reported sleep duration and hypertension: results of a Chinese prospective cohort study. _Clin. Exp. Hypertens._ 38, 514–519 (2016). Article  PubMed 

Google Scholar  * Kim, J. & Jo, I. Age-dependent association between sleep duration and hypertension in the adult Korean population. _Am. J. Hypertens._ 23, 1286–1291 (2010). Article 

PubMed  Google Scholar  * Fang, J. et al. Association of sleep duration and hypertension among US adults varies by age and sex. _Am. J. Hypertens._ 25, 335–341 (2012). Article  PubMed 

Google Scholar  * Stranges, S. et al. A population-based study of reduced sleep duration and hypertension: the strongest association may be in premenopausal women. _J. Hypertens._ 28,

896–902 (2010). Article  CAS  PubMed  Google Scholar  * Javaheri, S., Storfer-Isser, A., Rosen, C. L. & Redline, S. Sleep quality and elevated blood pressure in adolescents.

_Circulation_ 118, 1034–1040 (2008). Article  PubMed  PubMed Central  Google Scholar  * Ramos, A. R. et al. Sleep patterns and hypertension using actigraphy in the Hispanic Community Health

Study/Study of Latinos. _Chest_ 153, 87–93 (2018). Article  PubMed  Google Scholar  * Haack, M. et al. Increasing sleep duration to lower beat-to-beat blood pressure — a pilot study. _J.

Sleep Res._ 22, 295–304 (2013). Article  PubMed  Google Scholar  * Acar, G. et al. Acute sleep deprivation in healthy adults is associated with a reduction in left atrial early diastolic

strain rate. _Sleep Breath._ 17, 975–983 (2013). Article  PubMed  Google Scholar  * Cakici, M. et al. Negative effects of acute sleep deprivation on left ventricular functions and cardiac

repolarization in healthy young adults. _Pacing Clin. Electrophysiol._ 38, 713–722 (2015). Article  PubMed  Google Scholar  * Ozer, O. et al. Acute sleep deprivation is associated with

increased QT dispersion in healthy young adults. _Pacing Clin. Electrophysiol._ 31, 979–984 (2008). Article  PubMed  Google Scholar  * Miner, S. E. S. et al. Sleep disruption is associated

with increased ventricular ectopy and cardiac arrest in hospitalized adults. _Sleep_ 39, 927–935 (2016). Article  PubMed  PubMed Central  Google Scholar  * Ayas, N. T. et al. A prospective

study of sleep duration and coronary heart disease in women. _Arch. Intern. Med._ 163, 205–209 (2003). Article  PubMed  Google Scholar  * Chandola, T., Ferrie, J. E., Perski, A., Akbaraly,

T. & Marmot, M. G. The effect of short sleep duration on coronary heart disease risk is greatest among those with sleep disturbance: a prospective study from the Whitehall II cohort.

_Sleep_ 33, 739–744 (2010). Article  PubMed  PubMed Central  Google Scholar  * Liu, Y., Wheaton, A. G., Chapman, D. P. & Croft, J. B. Sleep duration and chronic diseases among US adults

age 45 years and older: evidence from the 2010 Behavioral Risk Factor Surveillance System. _Sleep_ 36, 1421–1427 (2013). Article  PubMed  PubMed Central  Google Scholar  * King, C. R. et al.

Short sleep duration and incident coronary artery calcification. _JAMA_ 300, 2859–2866 (2008). Article  CAS  PubMed  PubMed Central  Google Scholar  * Barger, L. K. et al. Short sleep

duration, obstructive sleep apnea, shiftwork, and the risk of adverse cardiovascular events in patients after an acute coronary syndrome. _J. Am. Heart Assoc._ 6, e006959 (2017). Article 

PubMed  PubMed Central  Google Scholar  * McHill, A. W. & Wright, K. P. J. Role of sleep and circadian disruption on energy expenditure and in metabolic predisposition to human obesity

and metabolic disease. _Obes. Rev._ 18 (Suppl. 1), 15–24 (2017). Article  PubMed  Google Scholar  * Rafalson, L., Donahue, R. P. & Trevisan, M. Short sleep duration is associated with

the development of impaired fasting glucose: the Western New York Health study. _Ann. Epidemiol._ 20, 883–889 (2010). Article  PubMed  PubMed Central  Google Scholar  * Spiegel, K., Tasali,

E., Leproult, R. & Van Cauter, E. Effects of poor and short sleep on glucose metabolism and obesity risk. _Nat. Rev. Endocrinol._ 5, 253–261 (2009). Article  CAS  PubMed  PubMed Central

  Google Scholar  * Cohen, D. A. et al. Uncovering residual effects of chronic sleep loss on human performance. _Sci. Transl. Med._ 2, 14ra3 (2010). Article  PubMed  PubMed Central  Google

Scholar  * Buxton, O. M. et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. _Sci. Transl. Med_. 4, 129ra43 (2012). Article 

PubMed  PubMed Central  Google Scholar  * Broussard, J. L., Ehrmann, D. A., Van Cauter, E., Tasali, E. & Brady, M. J. Impaired insulin signaling in human adipocytes after experimental

sleep restriction: a randomized, crossover study. _Ann. Intern. Med._ 157, 549–557 (2012). Article  PubMed  PubMed Central  Google Scholar  * Cappuccio, F. P. & Miller, M. A. Sleep and

cardio-metabolic disease. _Curr. Cardiol. Rep._ 19, 110 (2017). Article  PubMed  PubMed Central  Google Scholar  * Al Khatib, H. K., Harding, S. V., Darzi, J. & Pot, G. K. The effects of

partial sleep deprivation on energy balance: a systematic review and meta-analysis. _Eur. J. Clin. Nutr._ 71, 614–624 (2017). Article  CAS  PubMed  Google Scholar  * Nuyujukian, D. S. et

al. Sleep duration and diabetes risk in American Indian and Alaska Native participants of a lifestyle intervention project. _Sleep_ 39, 1919–1926 (2016). Article  PubMed  PubMed Central 

Google Scholar  * Heianza, Y. et al. Role of sleep duration as a risk factor for Type 2 diabetes among adults of different ages in Japan: the Niigata Wellness study. _Diabet. Med._ 31,

1363–1367 (2014). Article  CAS  PubMed  Google Scholar  * Beihl, D. A., Liese, A. D. & Haffner, S. M. Sleep duration as a risk factor for incident type 2 diabetes in a multiethnic

cohort. _Ann. Epidemiol._ 19, 351–357 (2009). Article  PubMed  Google Scholar  * Bromley, L. E., Booth, J. N. 3rd, Kilkus, J. M., Imperial, J. G. & Penev, P. D. Sleep restriction

decreases the physical activity of adults at risk for type 2 diabetes. _Sleep_ 35, 977–984 (2012). Article  PubMed  PubMed Central  Google Scholar  * Booth, J. N. et al. Reduced physical

activity in adults at risk for type 2 diabetes who curtail their sleep. _Obesity_ 20, 278–284 (2012). Article  PubMed  Google Scholar  * Leproult, R., Deliens, G., Gilson, M. & Peigneux,

P. Beneficial impact of sleep extension on fasting insulin sensitivity in adults with habitual sleep restriction. _Sleep_ 38, 707–715 (2015). Article  PubMed  PubMed Central  Google Scholar

  * Krueger, P. M., Reither, E. N., Peppard, P. E., Burger, A. E. & Hale, L. Cumulative exposure to short sleep and body mass outcomes: a prospective study. _J. Sleep Res._ 24, 629–638

(2015). Article  PubMed  PubMed Central  Google Scholar  * Li, L., Zhang, S., Huang, Y. & Chen, K. Sleep duration and obesity in children: a systematic review and meta-analysis of

prospective cohort studies. _J. Paediatr. Child Health_ 53, 378–385 (2017). Article  PubMed  Google Scholar  * Morrissey, B. et al. Sleep duration and risk of obesity among a sample of

Victorian school children. _BMC Publ_. _Health_ 16, 245 (2016). Google Scholar  * Halal, C. S. E. et al. Short sleep duration in the first years of life and obesity/overweight at age 4

years: a birth cohort study. _J. Pediatr._ 168, 99–103.e3 (2016). Article  PubMed  PubMed Central  Google Scholar  * Martinez, S. M. et al. Is it time for bed? Short sleep duration increases

risk of obesity in Mexican American children. _Sleep Med._ 15, 1484–1489 (2014). Article  PubMed  PubMed Central  Google Scholar  * Taveras, E. M., Gillman, M. W., Pena, M.-M., Redline, S.

& Rifas-Shiman, S. L. Chronic sleep curtailment and adiposity. _Pediatrics_ 133, 1013–1022 (2014). Article  PubMed  PubMed Central  Google Scholar  * Martinez, S. M. et al. Short sleep

duration is associated with eating more carbohydrates and less dietary fat in Mexican American children. _Sleep_ 40, zsw057 (2017). Article  Google Scholar  * Beebe, D. W. et al. Dietary

intake following experimentally restricted sleep in adolescents. _Sleep_ 36, 827–834 (2013). Article  PubMed  PubMed Central  Google Scholar  * Mullins, E. N. et al. Acute sleep restriction

increases dietary intake in preschool-age children. _J. Sleep Res._ 26, 48–54 (2017). Article  PubMed  Google Scholar  * Garaulet, M. et al. Short sleep duration is associated with increased

obesity markers in European adolescents: effect of physical activity and dietary habits. The HELENA study. _Int. J. Obes._ 35, 1308–1317 (2011). Article  CAS  Google Scholar  * Wang, F. et

al. Sleep duration and overweight/obesity in preschool-aged children: a prospective study of up to 48,922 children of the Jiaxing birth cohort. _Sleep_ 39, 2013–2019 (2016). Article  PubMed

  PubMed Central  Google Scholar  * Cespedes, E. M. et al. Chronic insufficient sleep and diet quality: contributors to childhood obesity. _Obesity_ 24, 184–190 (2016). Article  PubMed 

Google Scholar  * Kobayashi, D., Takahashi, O., Deshpande, G. A., Shimbo, T. & Fukui, T. Association between weight gain, obesity, and sleep duration: a large-scale 3-year cohort study.

_Sleep Breath._ 16, 829–833 (2012). Article  PubMed  Google Scholar  * Haghighatdoost, F., Karimi, G., Esmaillzadeh, A. & Azadbakht, L. Sleep deprivation is associated with lower diet

quality indices and higher rate of general and central obesity among young female students in Iran. _Nutrition_ 28, 1146–1150 (2012). Article  PubMed  Google Scholar  * Sun, W. et al. Sleep

duration associated with body mass index among Chinese adults. _Sleep Med._ 16, 612–616 (2015). Article  PubMed  Google Scholar  * Kim, K., Shin, D., Jung, G.-U., Lee, D. & Park, S. M.

Association between sleep duration, fat mass, lean mass and obesity in Korean adults: the fourth and fifth Korea National Health and Nutrition Examination surveys. _J. Sleep Res._ 26,

453–460 (2017). Article  PubMed  Google Scholar  * Theorell-Haglow, J., Berglund, L., Berne, C. & Lindberg, E. Both habitual short sleepers and long sleepers are at greater risk of

obesity: a population-based 10-year follow-up in women. _Sleep Med._ 15, 1204–1211 (2014). Article  PubMed  Google Scholar  * Sperry, S. D., Scully, I. D., Gramzow, R. H. & Jorgensen, R.

S. Sleep Duration and waist circumference in adults: a meta-analysis. _Sleep_ 38, 1269–1276 (2015). Article  PubMed  PubMed Central  Google Scholar  * Chaput, J.-P., McNeil, J., Despres,

J.-P., Bouchard, C. & Tremblay, A. Short sleep duration as a risk factor for the development of the metabolic syndrome in adults. _Prev. Med._ 57, 872–877 (2013). Article  PubMed  Google

Scholar  * Thomson, C. A. et al. Relationship between sleep quality and quantity and weight loss in women participating in a weight-loss intervention trial. _Obesity_ 20, 1419–1425 (2012).

Article  PubMed  Google Scholar  * Chaput, J.-P. & Dutil, C. Lack of sleep as a contributor to obesity in adolescents: impacts on eating and activity behaviors. _Int. J. Behav. Nutr.

Phys. Act._ 13, 103 (2016). Article  PubMed  PubMed Central  Google Scholar  * Tasali, E., Chapotot, F., Wroblewski, K. & Schoeller, D. The effects of extended bedtimes on sleep duration

and food desire in overweight young adults: a home-based intervention. _Appetite_ 80, 220–224 (2014). Article  PubMed  PubMed Central  Google Scholar  * Lucassen, E. A. et al. Sleep

extension improves neurocognitive functions in chronically sleep-deprived obese individuals. _PLOS ONE_ 9, e84832 (2014). Article  PubMed  PubMed Central  CAS  Google Scholar  * Scheer, F.

A. J. L., Van Montfrans, G. A., Van Someren, E. J. W., Mairuhu, G. & Buijs, R. M. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension.

_Hypertension_ 43, 192–197 (2004). Article  CAS  PubMed  Google Scholar  * Grossman, E. et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. _Am. J. Med._

119, 898–902 (2006). Article  CAS  PubMed  Google Scholar  * Sateia, M. J. International classification of sleep disorders - third edition. _Chest_ 146, 1387–1394 (2014). Article  PubMed 

Google Scholar  Download references ACKNOWLEDGEMENTS REVIEWER INFORMATION _Nature Reviews Cardiology_ thanks M. A. Grandner, O. Oldenburg and the other anonymous reviewer(s) for their

contribution to the peer review of this work. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Internal Medicine, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico and

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy Eleonora Tobaldini, Elisa M. Fiorelli, Monica Solbiati, Giorgio Costantino & Nicola Montano *

Child Neuropsychiatry Unit, IRCCS Istituto Giannina Gaslini, DINOGMI, University of Genoa, Genoa, Italy Lino Nobili Authors * Eleonora Tobaldini View author publications You can also search

for this author inPubMed Google Scholar * Elisa M. Fiorelli View author publications You can also search for this author inPubMed Google Scholar * Monica Solbiati View author publications

You can also search for this author inPubMed Google Scholar * Giorgio Costantino View author publications You can also search for this author inPubMed Google Scholar * Lino Nobili View

author publications You can also search for this author inPubMed Google Scholar * Nicola Montano View author publications You can also search for this author inPubMed Google Scholar

CONTRIBUTIONS E.T., E.M.F., and N.M. researched data for the article and wrote the manuscript. E.T., M.S., G.C., L.N., and N.M. discussed the content of the article, and E.M.F., M.S., G.C.,

L.N., and N.M. reviewed and edited it before submission. CORRESPONDING AUTHOR Correspondence to Nicola Montano. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing

interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. GLOSSARY *

Actigraphy A method for noninvasive monitoring of rest and activity cycles in humans via a wrist-worn device; although actigraphy is not the gold standard for diagnosing a sleep disorder, it

is a useful research tool because data can be recorded inexpensively and in a natural sleep environment. * Polysomnography A type of sleep study, based on the simultaneous recording of

several biological functions during sleep (electrocardiogram, respiration, brain activity, muscles, and ocular movements); in clinical practice, polysomnography is the gold-standard

technique for recording sleep and diagnosing sleep disorders. * Non-dipper profile In ambulatory blood-pressure monitoring, a non-dipper profile is characterized by the absence of a

physiological fall in blood pressure during night time compared with daytime. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Tobaldini, E., Fiorelli,

E.M., Solbiati, M. _et al._ Short sleep duration and cardiometabolic risk: from pathophysiology to clinical evidence. _Nat Rev Cardiol_ 16, 213–224 (2019).

https://doi.org/10.1038/s41569-018-0109-6 Download citation * Published: 08 November 2018 * Issue Date: April 2019 * DOI: https://doi.org/10.1038/s41569-018-0109-6 SHARE THIS ARTICLE Anyone

you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the

Springer Nature SharedIt content-sharing initiative