bims-minfam 2022-09-18 papers

J Physiol. 2022 Sep 16.

Drugs, clocks and exercise in aging: hype and hope, facts and fiction.

Aging is a biological process that is linked to a functional decline, ultimately resulting in death. Large interindividual differences exist in terms of life- and healthspan, representing life expectancy and the number of years spent in the absence of major diseases, respectively. The genetic and molecular mechanisms that are involved in the regulation of the aging process, and those that render age the main risk factor for many diseases are still poorly understood. Nevertheless, a growing number of compounds have been put forward to affect this process. However, for scientists and laypeople alike, it is difficult to separate facts from fiction, and hype from hope. In this review, we discuss the currently pursued pharmacological anti-aging approaches. These are compared to non-pharmacological interventions, some of which confer powerful effects on health and well-being, in particular an active lifestyle and exercise. Moreover, functional parameters and biological clocks as well as other molecular marks are compared in terms of predictive power of morbidity and mortality. Then, conceptual aspects and roadblocks in the development of anti-aging drugs are outlined. Finally, an overview on current and future strategies to mitigate age-related pathologies and the extension of life- and healthspan is provided. Abstract figure legend Modulation of the human aging process. Aging leads to a functional decline with increased frailty and morbidity, ultimately resulting in death. This process is affected by the genetic setup, epigenetic predisposition, and random events, leading to large interindividual differences in regard to health, well-being and life expectancy. Exercise, diet and other lifestyle-based interventions as well as societal measures can help to maximize the chance for healthy aging. Proposed drugs, cellular, epigenetic, and other non-pharmacological approaches such as caloric restriction await validation for safe and efficacious application in human geroprotection. This article is protected by copyright. All rights reserved.

Keywords: aging; exercise; healthspan; lifespan; longevity; rapamycin; rejuvenation; reprogramming; senolytics

DOI: https://doi.org/10.1113/JP282887

J Am Heart Assoc. 2022 Sep 14. e020735

Correction to: Age-Dependent Relationship of Hypertension Subtypes With Incident Heart Failure.

DOI: https://doi.org/10.1161/JAHA.121.020735

Lancet Healthy Longev. 2021 Nov;pii: S2666-7568(21)00184-7. [Epub ahead of print]2(11): e736-e745

Frailty assessment in the care of older people with haematological malignancies.

Valentin Goede, Nina Rosa Neuendorff, Ralf-Joachim Schulz, Ana-Isabel Hormigo, Francisco Javier Martinez-Peromingo, Raul Cordoba.

Frailty, defined as an age-related state of increased vulnerability to acute stressors, is a major challenge in the care of older people with haematological malignancies. Growing evidence from multiple studies suggests that a systematic evaluation of frailty in these patients by use of appropriate assessment tools might help clinicians to make appropriate treatment decisions and initiate frailty interventions. Here, we summarise current knowledge on the origin, decision relevance, assessment methods, and possible treatments of frailty in older people with haematological malignancies. Practical advice is provided on how to care for those with frailty and blood cancer.

DOI: https://doi.org/10.1016/S2666-7568(21)00184-7

Nat Commun. 2022 Sep 12. 13(1): 5350

Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease.

Age-related changes to the genome-wide DNA methylation (DNAm) pattern observed in blood are well-documented. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study (CHS) participants, with replication in 2655 Atherosclerosis Risk in Communities (ARIC) Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations associated with these two leading CHIP genes may promote the risk for CAD.

DOI: https://doi.org/10.1038/s41467-022-33093-3