Journal of Internal Medicine最新文献

The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers to the number of years an individual can live in good health. From a gerontological viewpoint, the mission is to extend the life spent in good health, promoting well-being and minimizing the impact of aging-related diseases to slow the aging process. Biologically, aging is a malleable process characterized by an intra- and inter-individual heterogeneous and dynamic balance between accumulating damage and repair mechanisms. Cellular senescence is a key component of this process, with senescent cells accumulating in different tissues and organs, leading to aging and age-related disease susceptibility over time. Removing senescent cells from the body or slowing down the burden rate has been proposed as an efficient way to reduce age-dependent deterioration. In animal models, senotherapeutic molecules can extend life expectancy and lifespan by either senolytic or senomorphic activity. Much research shows that dietary and physical activity-driven lifestyle interventions protect against senescence. This narrative review aims to summarize the current knowledge on targeting senescent cells to reduce the risk of age-related disease in animal models and their translational potential for humans. We focused on studies that have examined the potential role of senotherapeutics in slowing the aging process and modifying age-related disease burdens. The review concludes with a general discussion of the mechanisms underlying this unique trajectory and its implications for future research.

The emergence of the planetary health approach was highlighted by the report of The Rockefeller Foundation-Lancet Commission on Planetary Health in 2015 and changed how we comprehend human well-being. The report advocates integrating the health of other living beings and Earth's natural systems as intrinsic components of human health. Drawing on over three decades of experience in respiratory epidemiology and environmental health, this article outlines how my perspective on human health underwent a transformative shift upon reading the abovementioned report. The planetary health approach offers a lens through which human health issues and potential solutions can be understood within the context of the Anthropocene. It addresses the pressing existential challenges arising from humanity's transgression of planetary limits. Embracing the planetary health paradigm within the field of health sciences can catalyze transformative changes essential for cultivating a sustainable and equitable future.

Pharmacogenomics is the examination of how genetic variation influences drug metabolism and response, in terms of both efficacy and safety. In cardiovascular disease, patient-specific diplotypes determine phenotypes, thereby influencing the efficacy and safety of drug treatments, including statins, antiarrhythmics, anticoagulants and antiplatelets. Notably, polymorphisms in key genes, such as CYP2C9, CYP2C19, VKORC1 and SLCO1B1, significantly impact the outcomes of treatment with clopidogrel, warfarin and simvastatin. Furthermore, the CYP2C19 polymorphism influences the pharmacokinetics and safety of the novel hypertrophic cardiomyopathy inhibitor, mavacamten. In this review, we critically assess the clinical application of pharmacogenomics in cardiovascular disease and delineate present and future utilization of pharmacogenomics. This includes insights into identifying missing heritability, the integration of whole genome sequencing and the application of polygenic risk scores to enhance the precision of personalized drug therapy. Our discussion encompasses health economic analyses that underscore the cost benefits associated with pre-emptive genotyping for warfarin and clopidogrel treatments, albeit acknowledging the need for further research in this area. In summary, we contend that cardiovascular pharmacogenomic analyses are underpinned by a wealth of evidence, and implementation is already occurring for some of these gene–drug pairs, but as with any area of medicine, we need to continually gather more information to optimize the use of pharmacogenomics in clinical practice.

The Journal of Internal Medicine acknowledges the valuable contribution of the five individuals who in 2023 acted as external editors to make manuscript decisions when there was an internal conflict of interest.

The Editors

Asplund, Kjell

Borén, Jan

Cederholm, Tommy

de Faire, Ulf

Wiklund, Olov

Demographers have studied the Japanese mortality pattern since Japan became the most longevous population worldwide, half a century ago. Nutrition and lifestyle were considered by epidemiologists, gerontologists and other scientists as the most important reasons explaining the Japanese superiority. In Okinawa, the mortality pattern is even more exceptional, but few demographers have pointed out this exception. Other scientists proposed different explanations – for example some genetic characteristics, less salt and more animal protein in the food, a mild climate, a higher level of activity, a better consideration of the oldest in the population and, globally speaking, a more traditional lifestyle. At the end of the 1980s, lower improvements of mortality among young adults were identified in Okinawa. In 2002, Okinawa fell from the 4th to the 26th place in the ranking of the 47 Japanese prefectures by male life expectancy. This has been considered by the population of Okinawa as a ‘shock’. Our in-depth analysis of available life tables and associated mortality rates proves that the population of Okinawa is divided into two groups of generations: those born before World War II and those born after. The older generations clearly experience a highly favourable mortality pattern, whereas the younger generations show mortality levels that are definitively higher compared to mainland Japan. This contribution considers which factors may explain such a situation, including the plausible invalidation of the age of some oldest in the population. We plea for in-depth demographic age validation that will enhance all scientific findings so far and boost the exceptional longevity in Okinawa.