Aging is a major risk factor contributing to pathophysiological changes in the heart, yet its intrinsic mechanisms have been largely unexplored in primates. In this study, we investigated the hypertrophic and senescence phenotypes in the hearts of aged cynomolgus monkeys as well as the transcriptomic and proteomic landscapes of young and aged primate hearts. SIRT2 was identified as a key protein decreased in aged monkey hearts, and engineered SIRT2 deficiency in human pluripotent stem cell-derived cardiomyocytes recapitulated key senescence features of primate heart aging. Further investigations revealed that loss of SIRT2 in human cardiomyocytes led to the hyperacetylation of STAT3, which transcriptionally activated CDKN2B and, in turn, triggered cardiomyocyte degeneration. Intra-myocardial injection of lentiviruses expressing SIRT2 ameliorated age-related cardiac dysfunction in mice. Taken together, our study provides valuable resources for decoding primate cardiac aging and identifies the SIRT2-STAT3-CDKN2B regulatory axis as a potential therapeutic target against human cardiac aging and aging-related cardiovascular diseases.

BACKGROUND:The brain-heart axis is an intra- and bidirectional complex that links central nervous system dysfunction and cardiac dysfunction. In recent decades, brain-derived neurotrophic factor (BDNF) has emerged as a strategic molecule involved in both brain and cardiovascular disease (CVD). This systematic review of systematic reviews aimed to (1) identify and summarize the evidence for the BDNF genotype and BDNF concentration in CVD risk assessment, (2) evaluate the evidence for the use of BDNF as a biomarker of CVD recovery, and (3) evaluate rehabilitation approaches that can restore BDNF concentration. METHODS:A comprehensive search strategy was developed using PRISMA. The risk of bias was assessed via ROBIS. RESULTS:Seven studies were identified, most of which aimed to evaluate the role of BDNF in stroke patients. Only two systematic reviews examined the association of BDNF concentration and polymorphism in CVDs other than stroke. CONCLUSIONS:The overall evidence showed that BDNF plays a fundamental role in assessing the risk of CVD occurrence, because lower BDNF concentrations and rs6265 polymorphism are often associated with CVD. Nevertheless, much work remains to be carried out in current research to investigate how BDNF is modulated in different cardiovascular diseases and in different populations.

Brain microstates are defined as states with quasi-stable scalp activity topography and have been widely studied in literature. Whether those states are brain-specific or extend to the body level is unknown yet. We investigate the extension of cortical microstates to the peripheral autonomic nerve, specifically at the brain-heart axis level as a functional state of the central autonomic network. To achieve this, we combined Electroencephalographic (EEG) and heart rate variability (HRV) series from 36 healthy volunteers undergoing a cognitive workload elicitation after a resting state. Our results showed the existence of microstates at the functional brain-heart axis with spatio-temporal and quasi-stable states that exclusively pertained to the efferent direction from the brain to the heart. Some of the identified microstates are specific for neural or cardiovascular frequency bands, while others topographies are recurrent over the EEG and HRV spectra. Furthermore, some of the identified brain-heart microstates were associated with specific experimental conditions, while others were nonspecific to tasks. Our findings support the hypothesis that EEG microstates extend to the brain-heart axis level and may be exploited in future neuroscience and clinical research.