LAUSR

United Nations predicted that by 2050, about 16% of the world’s population will be over the age of 65[2]. Elderly people consuming high-fat or high-sugar diets have been associated with increased metabolic disturbances and allcause mortality [3, 4], while low calorie intake was one of the features of long-living populations [5]. In this paper, a team of scientists from multiple institutes developed a model of elderly heart failure by feeding non-human primate (NHP) cynomolgus monkeys a high-fat/high-sugar (HFSD) diet [1]. The study showed that a high-calorie diet disrupted metabolism and reduced heart function in older monkeys. The authors measured calcium sensitivity, actomyosin ATPase activity, and myofilament phosphorylation in dietinduced failing hearts of aged monkeys. These data are critical for elucidating the underlying mechanism of the reduced systolic function identified in these animals. The authors found that a gut-derived metabolite, trimethylamine N-oxide (TMAO), was significantly increased in aged monkeys fed with a HFSD. Elevated TMAO correlated with the severity of heart failure in humans, whereas addition of TMAO caused cardiac remodelling and ventricular dysfunction in experimental animals [6, 7]. The Editorial Team acknowledged the value of this exciting animal model of elderly heart failure, especially to explore the molecular mechanisms of elderly cardiac dysfunction upon high-fat diet administration[8]. Similar to humans in anatomy, physiology, metabolism, and genetics, NHPs have been used for decades to understand the pathogenesis of cardiovascular disease. Findings suggest that the biological effects of experimental diets on NHPs resemble those on humans [9]. Long-term calorie restriction studies in rhesus monkeys initiated in parallel by three primate research centers in the 1980s further support diet as a key factor in cardiac health [10]. However, the current understanding of the mechanism of diet-induced cardiac dysfunction in the elderly is mainly derived from rodent studies. To translate rodent research findings into clinical applications, we need NHP models that are more similar to the human condition in terms of physiology, anatomy, and genetics. The best paper of 2021 addresses this issue and provides a bridge for the translation of these findings to the clinics.