Journal of Genetics and Genomics

Targeting Ageing to Decrease Complex Non-Communicable Human Diseases

Jing-Dong J. Han, John R. Speakman

2014, 41(9): 457-458. doi: 10.1016/j.jgg.2014.09.002

Abstract (63) HTML PDF (0)

Abstract:

Rapamycin and Ageing: When, for How Long, and How Much?

Matt Kaeberlein

2014, 41(9): 459-463. doi: 10.1016/j.jgg.2014.06.009

Abstract (96) HTML PDF (2)

Abstract:

Circulating miRNAs in Ageing and Ageing-Related Diseases

Hwa Jin Jung, Yousin Suh

2014, 41(9): 465-472. doi: 10.1016/j.jgg.2014.07.003

Abstract (80) HTML PDF (2)

Abstract:
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ageing. Recently, extracellular miRNAs have been discovered in the bloodstream and bodily fluids. These miRNAs are shown to be secreted and circulating in microvesicles (MVs), or in complex with other factors such as RNA-binding proteins and high-density lipoprotein (HDL) particles. These cell-free, circulating miRNAs can be taken into and function as negative regulators of target genes in recipient cells. Here we review the biogenesis and uptake of circulating miRNAs as well as their profiles in ageing and ageing-related diseases. We discuss the emerging role of circulating miRNAs as biomarkers and therapeutic targets.

Towards Understanding RNA-Mediated Neurological Disorders

Ranhui Duan, Sumeet Sharma, Qiuping Xia, Kathryn Garber, Peng Jin

2014, 41(9): 473-484. doi: 10.1016/j.jgg.2014.08.003

Abstract (87) HTML PDF (0)

Abstract:
RNA-mediated mechanisms of disease pathogenesis in neurological disorders have been recognized in the context of certain repeat expansion disorders. This RNA-initiated neurodegeneration may play a more pervasive role in disease pathology beyond the classic dynamic mutation disorders. Here, we review the mechanisms of RNA toxicity and aberrant RNA processing that have been implicated in ageing-related neurological disorders. We focus on diseases with aberrant sequestration of RNA-binding proteins, bi-directional transcription, aberrant translation of repeat expansion RNA transcripts (repeat-associated non-ATG (RAN) translation), and the formation of pathological RNA:DNA secondary structure (R-loop). It is likely that repeat expansion disorders arise from common mechanisms caused by the repeat expansion mutations. However, the context of the repeat expansion determines the specific molecular consequences, leading to clinically distinct disorders.

Endothelial Cell Senescence and Age-Related Vascular Diseases

Xiao-Li Tian, Yang Li

2014, 41(9): 485-495. doi: 10.1016/j.jgg.2014.08.001

Abstract (95) HTML PDF (3)

Abstract:
Advanced age is an independent risk factor for ageing-related complex diseases, such as coronary artery disease, stroke, and hypertension, which are common but life threatening and related to the ageing-associated vascular dysfunction. On the other hand, patients with progeria syndromes suffer from serious atherosclerosis, suggesting that the impaired vascular functions may be critical to organismal ageing, or vice versa. However, it remains largely unknown how vascular cells, particularly endothelial cell, become senescent and how the senescence impairs the vascular functions and contributes to the age-related vascular diseases over time. Here, we review the recent progress on the characteristics of vascular ageing and endothelial cell senescence in vitro and in vivo, evaluate how genetic and environmental factors as well as autophagy and stem cell influence endothelial cell senescence and how the senescence contributes to the age-related vascular phenotypes, such as atherosclerosis and increased vascular stiffness, and explore the possibility whether we can delay the age-related vascular diseases through the control of vascular ageing.

Lifespan Modulation in Mice and the Confounding Effects of Genetic Background

Lorna Mulvey, Amy Sinclair, Colin Selman

2014, 41(9): 497-503. doi: 10.1016/j.jgg.2014.06.002

Abstract (69) HTML PDF (0)

Abstract:
We are currently in the midst of a revolution in ageing research, with several dietary, genetic and pharmacological interventions now known to modulate ageing in model organisms. Excitingly, these interventions also appear to have beneficial effects on late-life health. For example, dietary restriction (DR) has been shown to slow the incidence of age-associated cardiovascular disease, metabolic disease, cancer and brain ageing in non-human primates and has been shown to improve a range of health indices in humans. While the idea that DR's ability to extend lifespan is often thought of as being universal, studies in a range of organisms, including yeast, mice and monkeys, suggest that this may not actually be the case. The precise reasons underlying these differential effects of DR on lifespan are currently unclear, but genetic background may be an important factor in how an individual responds to DR. Similarly, recent findings also suggest that the responsiveness of mice to specific genetic or pharmacological interventions that modulate ageing may again be influenced by genetic background. Consequently, while there is a clear driver to develop interventions to improve late-life health and vitality, understanding precisely how these act in response to particular genotypes is critical if we are to translate these findings to humans. We will consider of the role of genetic background in the efficacy of various lifespan interventions and discuss potential routes of utilising genetic heterogeneity to further understand how particular interventions modulate lifespan and healthspan.

Using Doubly-Labeled Water to Measure Energy Expenditure in an Important Small Ectotherm Drosophila melanogaster

Matthew D.W. Piper, Colin Selman, John R. Speakman, Linda Partridge

2014, 41(9): 505-512. doi: 10.1016/j.jgg.2014.07.004

Abstract (69) HTML PDF (0)

Abstract:
Energy expenditure is a key variable in the study of ageing, and the fruit fly Drosophila melanogaster is a model organism that has been used to make step changes in our understanding of the ageing process. Standard methods for measurement of energy expenditure involve placing individuals in metabolic chambers where their oxygen consumption and CO₂ production can be quantified. These measurements require separating individuals from any social context, and may only poorly reflect the environment in which the animals normally live. The doubly-labeled water (DLW) method is an isotope-based technique for measuring energy expenditure which overcomes these problems. However, technical challenges mean that the smallest animals this method has been previously applied to weighed 50–200 mg. We overcame these technical challenges to measure energy demands inDrosophila weighing 0.78 mg. Mass-specific energy expenditure varied between 43 and 65 mW·g⁻¹. These estimates are considerably higher than estimates using indirect calorimetry of Drosophila in small metabolic chambers (around 18 mW·g⁻¹). The methodology we have established extends downwards by three orders of magnitude the size of animals that can be measured using DLW. This approach may be of considerable value in future ageing research attempting to understand the genetic and genomic basis of ageing.

2014 Vol. 41, No. 9