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John C Newman, Sofiya Milman, Shahrukh K Hashmi, Steve N Austad, James L Kirkland, Jeffrey B Halter, Nir Barzilai
Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use...
August 16, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Derek M Huffman, Jamie N Justice, Michael B Stout, James L Kirkland, Nir Barzilai, Steven N Austad
Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains...
August 16, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Jamie Justice, Jordan D Miller, John C Newman, Shahrukh K Hashmi, Jeffrey Halter, Steve N Austad, Nir Barzilai, James L Kirkland
Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions-a concept dubbed the "geroscience hypothesis." Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging...
August 16, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Felipe Sierra
No abstract text is available yet for this article.
August 16, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Christin E Burd, Matthew S Gill, Laura J Niedernhofer, Paul D Robbins, Steven N Austad, Nir Barzilai, James L Kirkland
Through the progress of basic science research, fundamental mechanisms that contribute to age-related decline are being described with increasing depth and detail. Although these efforts have identified new drug targets and compounds that extend life span in model organisms, clinical trials of therapeutics that target aging processes remain scarce. Progress in aging research is hindered by barriers associated with the translation of basic science discoveries into the clinic. This report summarizes discussions held at a 2014 Geroscience Network retreat focused on identifying hurdles that currently impede the preclinical development of drugs targeting fundamental aging processes...
August 16, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Alexander M Vaiserman, Oleh V Lushchak, Alexander K Koliada
Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness...
November 2016: Ageing Research Reviews
Simon C Johnson, Matt Kaeberlein
Experimental geroscience has identified rapamycin as a top candidate for promoting healthy aging and longevity in mammals. As multiple independent studies have successfully reproduced the lifespan and healthspan promoting effects of rapamycin, the focus has shifted to possible translational use. While a promising compound, clinical use of rapamycin is limited by concerns of side effects associated with the drug. Studies aimed at defining optimal dosage regimen, delivery route, and formulation will allow for benefits to be maximized while reducing side effects...
July 1, 2016: Oncotarget
Simon Melov
For decades, researchers in the biology of aging have focused on defining mechanisms that modulate aging by primarily studying a single metric, sometimes described as the "gold standard" lifespan. Increasingly, geroscience research is turning towards defining functional domains of aging such as the cardiovascular system, skeletal integrity, and metabolic health as being a more direct route to understand why tissues decline in function with age. Each model used in aging research has strengths and weaknesses, yet we know surprisingly little about how critical tissues decline in health with increasing age...
2016: F1000Research
Matt Kaeberlein, Kate E Creevy, Daniel E L Promislow
Studies of the basic biology of aging have identified several genetic and pharmacological interventions that appear to modulate the rate of aging in laboratory model organisms, but a barrier to further progress has been the challenge of moving beyond these laboratory discoveries to impact health and quality of life for people. The domestic dog, Canis familiaris, offers a unique opportunity for surmounting this barrier in the near future. In particular, companion dogs share our environment and play an important role in improving the quality of life for millions of people...
August 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Luigi Ferrucci, Rachel Cooper, Michelle Shardell, Eleanor M Simonsick, Jennifer A Schrack, Diana Kuh
Mobility is the most studied and most relevant physical ability affecting quality of life with strong prognostic value for disability and survival. Natural selection has built the "engine" of mobility with great robustness, redundancy, and functional reserve. Efficient patterns of mobility can be acquired during development even by children affected by severe impairments. Analogously, age-associated impairments in mobility-related physiological systems are compensated and overt limitations of mobility only occur when the severity can no longer be compensated...
September 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Felipe Sierra
Research on the biology of aging has accelerated rapidly in the last two decades. It is now at the point where translation of the findings into useful approaches to improve the health of the elderly population seems possible. In trying to fill that gap, a new field termed geroscience will be articulated here that attempts to identify the biological underpinnings for the age-dependency of most chronic diseases. Herein, I will review the major conceptual issues leading to the formulation of geroscience as a field, as well as give examples of current areas of inquiry in which basic aging biology research could lead to therapeutic approaches to address age-related chronic diseases, not one at a time, but most of them in unison...
April 2016: Cold Spring Harbor Perspectives in Medicine
L Harkema, S A Youssef, A de Bruin
Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging...
March 2016: Veterinary Pathology
P M Treuting, J M Snyder, Y Ikeno, P N Schofield, J M Ward, J P Sundberg
Pathology is a discipline of medicine that adds great benefit to aging studies of rodents by integrating in vivo, biochemical, and molecular data. It is not possible to diagnose systemic illness, comorbidities, and proximate causes of death in aging studies without the morphologic context provided by histopathology. To date, many rodent aging studies do not utilize end points supported by systematic necropsy and histopathology, which leaves studies incomplete, contradictory, and difficult to interpret. As in traditional toxicity studies, if the effect of a drug, dietary treatment, or altered gene expression on aging is to be studied, systematic pathology analysis must be included to determine the causes of age-related illness, moribundity, and death...
March 2016: Veterinary Pathology
Matt Kaeberlein, Peter S Rabinovitch, George M Martin
Age is the greatest risk factor for nearly every major cause of mortality in developed nations. Despite this, most biomedical research focuses on individual disease processes without much consideration for the relationships between aging and disease. Recent discoveries in the field of geroscience, which aims to explain biological mechanisms of aging, have provided insights into molecular processes that underlie biological aging and, perhaps more importantly, potential interventions to delay aging and promote healthy longevity...
December 4, 2015: Science
Brian K Kennedy, Shelley L Berger, Anne Brunet, Judith Campisi, Ana Maria Cuervo, Elissa S Epel, Claudio Franceschi, Gordon J Lithgow, Richard I Morimoto, Jeffrey E Pessin, Thomas A Rando, Arlan Richardson, Eric E Schadt, Tony Wyss-Coray, Felipe Sierra
Mammalian aging can be delayed with genetic, dietary, and pharmacologic approaches. Given that the elderly population is dramatically increasing and that aging is the greatest risk factor for a majority of chronic diseases driving both morbidity and mortality, it is critical to expand geroscience research directed at extending human healthspan.
November 6, 2014: Cell
Douglas R Seals, Simon Melov
Among individuals, biological aging leads to cellular and organismal dysfunction and an increased risk of chronic degenerative diseases and disability. This sequence of events in combination with the projected increases in the number of older adults will result in a worldwide healthcare burden with dire consequences. Superimposed on this setting are the adults now reaching traditional retirement ages--the baby boomers--a group that wishes to remain active, productive and physically and cognitively fit as they grow older...
September 2014: Aging
Claudio Franceschi, Judith Campisi
Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people...
June 2014: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Christopher B Newgard, Jeffrey E Pessin
The NIH Summit, Advances in Geroscience: Impact on Health Span and Chronic Disease, discusses several aspects of cellular degeneration that underlie susceptibility to chronic aging-associated diseases, morbidity, and mortality. In particular, the session on Metabolism focuses on the interrelationship between signal transduction, intermediary metabolism, and metabolic products and byproducts that contribute to pathophysiologic phenotypes and detrimental effects that occur during the aging process, thus leading to susceptibility to disease...
June 2014: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
John B Burch, Alison Deckhut Augustine, Leslie A Frieden, Evan Hadley, T Kevin Howcroft, Ron Johnson, Partap S Khalsa, Ronald A Kohanski, Xiao Ling Li, Francesca Macchiarini, George Niederehe, Young S Oh, Aaron C Pawlyk, Henry Rodriguez, Julia H Rowland, Grace L Shen, Felipe Sierra, Bradley C Wise
Population aging is unprecedented, without parallel in human history, and the 21st century will witness even more rapid aging than did the century just past. Improvements in public health and medicine are having a profound effect on population demographics worldwide. By 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60 ( Although we can reasonably expect to live longer today than past generations did, the age-related disease burden we will have to confront has not changed...
June 2014: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
T Kevin Howcroft, Judith Campisi, Germaine Buck Louis, Martyn T Smith, Bradley Wise, Tony Wyss-Coray, Alison Deckhut Augustine, Janet E McElhaney, Ron Kohanski, Felipe Sierra
The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation inAge-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan...
January 2013: Aging
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