Background:
Resistance training (RT) improves muscle strength and overall physical function in older adults. RT may be particularly important in the obese elderly who have compromised muscle ...function. Whether caloric restriction (CR) acts synergistically with RT to enhance function is unknown.
Objective:
As the primary goal of the Improving Muscle for Functional Independence Trial (I’M FIT), we determined the effects of adding CR for weight loss on muscle and physical function responses to RT in older overweight and obese adults.
Design:
I’M FIT was a 5-mo trial in 126 older (65–79 y) overweight and obese men and women who were randomly assigned to a progressive, 3-d/wk, moderate-intensity RT intervention with a weight-loss intervention (RT+CR) or without a weight-loss intervention (RT). The primary outcome was maximal knee extensor strength; secondary outcomes were muscle power and quality, overall physical function, and total body and thigh compositions.
Results:
Body mass decreased in the RT+CR group but not in the RT group. Fat mass, percentage of fat, and all thigh fat volumes decreased in both groups, but only the RT+CR group lost lean mass. Adjusted postintervention body- and thigh-composition measures were all lower with RT+CR except intermuscular adipose tissue (IMAT). Knee strength, power, and quality and the 4-m gait speed increased similarly in both groups. Adjusted postintervention means for a 400-m walk time and self-reported disability were better with RT+CR with no group differences in other functional measures, including knee strength. Participants with a lower percentage of fat and IMAT at baseline exhibited a greater improvement in the 400-m walk and knee strength and power.
Conclusions:
RT improved body composition (including reducing IMAT) and muscle strength and physical function in obese elderly, but those with higher initial adiposity experienced less improvement. The addition of CR during RT improves mobility and does not compromise other functional adaptations to RT. These findings support the incorporation of RT into obesity treatments for this population regardless of whether CR is part of the treatment. This trial was registered at
clinicaltrials.gov
as NCT01049698.
Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, ...which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research.
The structure and integrity of the ageing brain is interchangeably linked to physical health, and cardiometabolic risk factors (CMRs) are associated with dementia and other brain disorders. In this ...mixed cross‐sectional and longitudinal study (interval mean = 19.7 months), including 790 healthy individuals (mean age = 46.7 years, 53% women), we investigated CMRs and health indicators including anthropometric measures, lifestyle factors, and blood biomarkers in relation to brain structure using MRI‐based morphometry and diffusion tensor imaging (DTI). We performed tissue specific brain age prediction using machine learning and performed Bayesian multilevel modeling to assess changes in each CMR over time, their respective association with brain age gap (BAG), and their interaction effects with time and age on the tissue‐specific BAGs. The results showed credible associations between DTI‐based BAG and blood levels of phosphate and mean cell volume (MCV), and between T1‐based BAG and systolic blood pressure, smoking, pulse, and C‐reactive protein (CRP), indicating older‐appearing brains in people with higher cardiometabolic risk (smoking, higher blood pressure and pulse, low‐grade inflammation). Longitudinal evidence supported interactions between both BAGs and waist‐to‐hip ratio (WHR), and between DTI‐based BAG and systolic blood pressure and smoking, indicating accelerated ageing in people with higher cardiometabolic risk (smoking, higher blood pressure, and WHR). The results demonstrate that cardiometabolic risk factors are associated with brain ageing. While randomized controlled trials are needed to establish causality, our results indicate that public health initiatives and treatment strategies targeting modifiable cardiometabolic risk factors may also improve risk trajectories and delay brain ageing.
The structure and integrity of the ageing brain is interchangeably linked to physical health, and cardiometabolic risk factors (CMRs). We investigated CMRs and health indicators including anthropometric measures, lifestyle factors, and blood biomarkers in relation to brain structure using MRI‐based morphometry and diffusion tensor imaging (DTI). Tissue‐specific brain age prediction using machine learning revealed older‐appearing brains and accelerated ageing in people with higher cardiometabolic risk.
It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells ...that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.
Aging results in the progressive accumulation of senescent cells in tissues that display loss of proliferative capacity and acquire a senescence-associated secretory phenotype (SASP). The tumor ...suppressor, p16
, which slows the progression of the cell cycle, is highly expressed in most senescent cells and the removal of p16-expressing cells has been shown to be beneficial to tissue health. Although much work has been done to assess the effects of cellular senescence on a variety of different organs, little is known about the effects on skeletal muscle and whether reducing cellular senescent load would provide a therapeutic benefit against age-related muscle functional decline. We hypothesized that whole-body ablation of p16-expressing cells in the advanced stages of life in mice would provide a therapeutic benefit to skeletal muscle structure and function. Treatment of transgenic p16-3MR mice with ganciclovir (GCV) from 20 to 26 months of age resulted in reduced p16 mRNA levels in muscle. At 26 months of age, the masses of tibialis anterior, extensor digitorum longus, gastrocnemius and quadriceps muscles were significantly larger in GCV-treated compared with vehicle-treated mice, but this effect was limited to male mice. Maximum isometric force for gastrocnemius muscles was also greater in GCV-treated male mice compared to controls. Further examination of muscles of GCV- and vehicle-treated mice showed fewer CD68-positive macrophages present in the tissue following GCV treatment. Plasma cytokine levels were also measured with only one, granulocyte colony stimulating factor (G-CSF), out of 22 chemokines analyzed was reduced in GCV-treated mice. These findings show that genetic ablation of p16
senescent cells provides moderate and sex specific therapeutic benefits to muscle mass and function.
Ageing in Place in Urban Environments considers together two major trends influencing economic and social life: population ageing on the one side and urbanisation on the other. Both have been ...identified as dominant demographic trends of the twenty-first century. Cities are where the majority of people of all ages now live and where they will spend their old age. Nevertheless, cities are typically imagined and structured with a younger, working-age population in mind while older people are rarely incorporated into the mainstream of thinking and planning around urban environments. Cities can contribute to vulnerability arising from high levels of population turnover, environmental problems, gentrification, and reduced availability of affordable housing. However, they can also provide innovative forms of support and services essential to promoting the quality of life of older people. Policies in Europe have emphasised the role of the local environment in promoting “ageing in place”, a term used to describe the goal of helping people to remain in their own homes and communities for as long as they wish. However, while this has been the dominant approach, the places in which older people are ageing have often proved to be challenging environments. The book explores the forces behind these developments and how older people have responded. Drawing upon approaches from social gerontology, urban studies, geography, and sociology, this book will be essential reading for researchers, policymakers, and practitioners searching for innovative ways to improve the lives of older people living in urban environments.
Catecholamine-induced lipolysis, the first step in the generation of energy substrates by the hydrolysis of triglycerides, declines with age. The defect in the mobilization of free fatty acids in the ...elderly is accompanied by increased visceral adiposity, lower exercise capacity, failure to maintain core body temperature during cold stress, and reduced ability to survive starvation. Although catecholamine signalling in adipocytes is normal in the elderly, how lipolysis is impaired in ageing remains unknown. Here we show that adipose tissue macrophages regulate the age-related reduction in adipocyte lipolysis in mice by lowering the bioavailability of noradrenaline. Unexpectedly, unbiased whole-transcriptome analyses of adipose macrophages revealed that ageing upregulates genes that control catecholamine degradation in an NLRP3 inflammasome-dependent manner. Deletion of NLRP3 in ageing restored catecholamine-induced lipolysis by downregulating growth differentiation factor-3 (GDF3) and monoamine oxidase A (MAOA) that is known to degrade noradrenaline. Consistent with this, deletion of GDF3 in inflammasome-activated macrophages improved lipolysis by decreasing levels of MAOA and caspase-1. Furthermore, inhibition of MAOA reversed the age-related reduction in noradrenaline concentration in adipose tissue, and restored lipolysis with increased levels of the key lipolytic enzymes adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Our study reveals that targeting neuro-immunometabolic signalling between the sympathetic nervous system and macrophages may offer new approaches to mitigate chronic inflammation-induced metabolic impairment and functional decline.
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