Environments as hypotheses in human aging research.

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations.

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Human Aging Research

Plastic & Reconstructive Surgery ◽

10.1097/00006534-198909000-00031 ◽

1989 ◽

Vol 84 (3) ◽

pp. 537

Author(s):

Barbara Kent ◽

Robert Butler ◽

Ross Rudolph

Keyword(s):

Human Aging ◽

Aging Research

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Bring Back the Rat!

The Journals of Gerontology Series A ◽

10.1093/gerona/glz298 ◽

2020 ◽

Vol 75 (3) ◽

pp. 405-415 ◽

Cited By ~ 8

Author(s):

Christy S Carter ◽

Arlan Richardson ◽

Derek M Huffman ◽

Steven Austad

Keyword(s):

Complete Characterization ◽

Human Aging ◽

Aging Research ◽

Laboratory Rat ◽

Basic Biology ◽

Biology Of Aging ◽

And Behavior ◽

Compare And Contrast

Abstract As 2020 is “The Year of the Rat” in the Chinese astrological calendar, it seems an appropriate time to consider whether we should bring back the laboratory rat to front-and-center in research on the basic biology of mammalian aging. Beginning in the 1970s, aging research with rats became common, peaking in 1992 but then declined dramatically by 2018 as the mouse became preeminent. The purpose of this review is to highlight some of the historical contributions as well as current advantages of the rat as a mammalian model of human aging, because we suspect at least a generation of researchers is no longer aware of this history or these advantages. Herein, we compare and contrast the mouse and rat in the context of several biological domains relevant to their use as appropriate models of aging: phylogeny/domestication, longevity interventions, pathology/physiology, and behavior/cognition. It is not the goal of this review to give a complete characterization of the differences between mice and rats, but to provide important examples of why using rats as well as mice is important to advance our understanding of the biology of aging.

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Human Aging research Concepts and Techniques, 1988

Topics in Geriatric Rehabilitation ◽

10.1097/00013614-198904000-00012 ◽

1989 ◽

Vol 4 (3) ◽

pp. 70-71

Author(s):

Carole Bernstein Lewis

Keyword(s):

Human Aging ◽

Aging Research

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Biological Anthropology and Human Aging: Some Current Directions in Aging Research

Annual Review of Anthropology ◽

10.1146/annurev.an.22.100193.002143 ◽

1993 ◽

Vol 22 (1) ◽

pp. 395-423 ◽

Cited By ~ 18

Author(s):

Douglas E. Crews

Keyword(s):

Biological Anthropology ◽

Human Aging ◽

Aging Research

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Quantification of biological aging in young adults

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1506264112 ◽

2015 ◽

Vol 112 (30) ◽

pp. E4104-E4110 ◽

Cited By ~ 306

Author(s):

Daniel W. Belsky ◽

Avshalom Caspi ◽

Renate Houts ◽

Harvey J. Cohen ◽

David L. Corcoran ◽

...

Keyword(s):

Young Adults ◽

Brain Aging ◽

Multiple Organ ◽

Biological Aging ◽

Research Translation ◽

Human Aging ◽

Aging Research ◽

Cross Sectional ◽

Age Related ◽

Organ Systems

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

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