David E. Harrison

Universal transcriptomic hallmarks of mammalian ageing and mortality

Alexander Tyshkovskiy, Daria Kholdina, Maria Davitadze, Adrian Molière et autres

, yet the underlying molecular mechanisms of this modulation remain unclear. Here we integrate more than 11,000 transcriptomes from more than 25 tissues across 4 mammals (mouse, rat, macaque and human) to develop accurate, interpretable rodent and multi-species biomarkers of chronological age …

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Dynamics of genetic and somatic trade-offs in ageing and mortality

Danny Arends, David G. Ashbrook, Suheeta Roy, Lu Lu et autres

DNA variants modulate mortality risks across an entire lifespan but their dynamic age-dependent effects have not been resolved in any species for either sex. Here we mapped variants that shape mortality using an actuarial approach, starting with a base population of 6,438 …

Dynamics of genetic and somatic trade-offs in ageing and mortality

Danny Arends, David G. Ashbrook, Suheeta Roy, Lu Lu et autres

DNA variants modulate mortality risks across an entire lifespan but their dynamic age-dependent effects have not been resolved in any species for either sex. Here we mapped variants that shape mortality using an actuarial approach, starting with a base population of 6,438 …

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Astaxanthin, meclizine, mitoglitazone, pioglitazone, alpha-ketoglutarate, mifepristone, methotrexate, and atorvastatin-telmisartan do not increase lifespan in UM-HET3 mice

Ron Korstanje, Randy Strong, Adam B. Salmon, Molly A. Bogue et autres

The Interventions Testing Program (ITP) evaluated eleven compounds in genetically heterogeneous UM-HET3 mice to assess their potential to extend lifespan. These interventions included both novel agents and previously tested compounds administered at novel doses or starting ages. Despite prior evidence suggesting lifespan …

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Analysis of lifespan across diversity outbred mouse studies identifies multiple longevity-associated loci

Martin N. Mullis, Kevin M. Wright, Anil Raj, Daniel M. Gatti et autres

Lifespan is an integrative phenotype whose genetic architecture is likely to highlight multiple processes with high impact on health and aging. Here, we conducted a genetic mega-analysis of longevity in Diversity Outbred (DO) mice that included 2,444 animals from 3 independently conducted …

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Age associated changes in behavioral and memory functions in genetically heterogeneous mice UM‐HET3

Harpreet Kaur, Bretton Badenoch, Peter C. Reifsnyder, Kristen M.S. O’Connell et autres

Abstract Background Previous studies have documented age‐related changes in behavior and cognitive functions and investigated the molecular changes in aging brain using inbred mouse strains such as C57BL/6, BALB/c etc. In this study using a genetically heterogenous mouse population (UM‐HET3) we investigated …

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Analysis of lifespan across Diversity Outbred mouse studies identifies multiple longevity-associated loci

Martin N. Mullis, Kevin M. Wright, Anil Raj, Daniel M. Gatti et autres

Lifespan is an integrative phenotype whose genetic architecture is likely to highlight multiple processes with high impact on health and aging. Here, we conduct a genetic meta-analysis of longevity in Diversity Outbred (DO) mice that includes 2,444 animals from three independently conducted …

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Low Utilization of Circulating Glucose after Food Withdrawal in Snell Dwarf Mice

Natasha L. Brooks, David E. Harrison, Carl F. Raetzsch, Simon Klebanov et autres

Glucose metabolism is altered in long-lived people and mice. Although it is clear that there is an association between altered glucose metabolism and longevity, it is not known whether this link is causal or not. Our current hypothesis is that decreased fasting …

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Histone modifications change with age, dietary restriction and rapamycin treatment in mouse brain

Hong Qian, Robin P. Ertl, Gang Greg Wang, Clinton M. Astle et autres

The risk of developing neurodegenerative disorders such as Alzheimer's disease (AD) increases dramatically with age. Understanding the underlying mechanisms of brain aging is crucial for developing preventative and/or therapeutic approaches for age-associated neurological diseases. Recently, it has been suggested that epigenetic factors, …

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Dietary Glycine Supplementation Extends Lifespan of Genetically Heterogeneous Mice

Joel Brind, Richard A. Miller, Randy Strong, David E. Harrison et autres

Preliminary experiments suggested lifespan extension by glycine supplementation (GlyS) without the growth inhibition seen with methionine restriction in Fisher 344 rats. This suggested that the benefit GlyS, rather than owing to increased methionine clearance (as was originally envisioned), was attributable to increased …

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Heritability of in vitro phenotypes exhibited by murine adipose-derived stromal cells

Zixuan Jiang, David E. Harrison, Makayla E. Parsons, Susan McClatchy et autres

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List of Contributors

Rolf Bodmer, Rochelle Buffenstein, Cheng Hao, Ying-Ann Chiao et autres