Abstract-Aging is a major risk factor for hypertension and cardiovascular disease. Accumulating evidence suggests that telomere length is a marker for biological aging of the cardiovascular system. Telomere length is determined by genetic and environmental factors. Studies in different racial populations are required to determine the prognostic value of telomere length in hypertension and cardiovascular diseases. The main objective of this study was to investigate the association between leukocyte telomere length and the risk and prognosis of hypertension in a Chinese population. A ging is a major risk factor for hypertension. Epidemiological studies have suggested that, relative to normotensive subjects, hypertensive subjects are at higher risk for the development of cardiovascular and cerebrovascular diseases than normotensive subjects. However, there is wide variation in the occurrence and manifestation of cardiovascular and cerebrovascular diseases in hypertensive patients, even in individuals with the same risk factor profiles. The reason for this interindividual variation is largely unknown but may be reflective of the variation in the rate of biological aging. 1 Telomere shortening represents one molecular mechanism that appears to contribute to cellular and organismal aging. Telomeres are specialized structures located at the ends of eukaryotic chromosomes. The main function of telomeres is to cap the chromosomal ends and to maintain genome stability and integrity. 2 When telomeres reach a critical short length, they lose capping function at the chromosomal ends, resulting in activation of DNA damage checkpoints. These checkpoints limit cell survival by induction of senescence or apoptosis. Telomere shortening limits the life span of human cells in culture 3 and occurs in various tissues during human aging. 4 Studies in mouse models have demonstrated a crucial role of telomere shortening in the impairment of the stem cell during organismal aging. 5,6 Studies in telomerase-deficient mice have also shown a direct link between telomere shortening and hypertension. 7 In humans, telomere shortening and cellular senescence have also been correlated with atherosclerosis and cardiovascular aging. 8 -10 Indeed, epidemiological studies have suggested that age-dependent telomere shortening could be used as a marker for essential hypertension 11,12 and related diseases or syndromes, such as insulin resistance, 13 diabetes mellitus, 14 obesity, 15 atherosclerosis, 16,17 coronary artery disease, 18,19 myocardial infarction, 20 and renal dysfunction. 21 Telomere length is determined by genetic 22-24 and environmental factors. [25][26][27][28] Differences in leukocyte telomere length have been observed between blacks and whites. 29 In addition,

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The reward of pain relief caused by acupuncture has been found to be clinically significant. However, the molecular mechanisms underlying acupuncture-induced reward of pain relief in chronic pain remain unclear and have not been analyzed in suitable preclinical models. Here, we investigated whether acupuncture could potentially induce the reward of pain relief and orexin neuronal signaling in the lateral hypothalamus (LH) and exhibit a possible role in electroacupuncture (EA)-induced reward in spared nerve injury (SNI) rats. Therefore, by using conditioned place preference (CPP) paradigm, we noticed that EA induced the preference for cues associated with EA-induced pain relief in the early, but not late, phase of chronic pain. These observations were different from the immediate antihyperalgesic effects of EA. c-Fos/orexin double labeling revealed that EA stimulation on 14 days but not on 28 days after SNI modeling activated greater numbers of c-Fos positive orexin neurons in the LH after the CPP test. Moreover, the administration of an orexin-A antagonist in the LH significantly blocked the reward effects of pain relief induced by EA. Furthermore, by using cholera toxin b subunit combined with c-Fos detection, we found that the orexin circuit from the LH to the nucleus accumbens (NAc) shell was significantly activated after EA induced CPP. Microinjection of the orexin antagonist into the NAc shell substantially attenuated the CPP induced by EA. Intravenous injection of low-dose orexin-A together with EA resulted in significantly greater antihyperalgesia effects and CPP scores. Together, these findings clearly demonstrated that LH orexin signaling could potentially play a critical role in the reward effects of pain relief induced by acupuncture. The observations of the present study extended our understanding of orexin signaling in the LH and its role in EA-induced reward, providing new insights into the mechanisms of acupuncture analgesia.