The 2 nd Annual Symposium of the Midwest Aging Consortium: The Future of Aging Research in the Midwestern United States.

While the average human lifespan continues to increase, there is little evidence that this is leading to a contemporaneous increase in "healthy years" experienced by our aging population. Consequently, many scientists focus their research on understanding the process of aging and trialing interventions that can promote healthspan. The 2021 Midwest Aging Consortium (MAC) consensus statement is to develop and further the understanding of aging and age-related disease using the wealth of expertise across universities in the Midwestern United States. This report summarizes the cutting-edge research covered in a virtual symposium held by a consortium of researchers in the Midwestern United States, spanning such topics as senescence biomarkers, serotonin induced DNA protection, immune system development, multi-system impacts of aging, neural decline following severe infection, the unique transcriptional impact of CR of different fat depots, the pivotal role of fasting in calorie restriction, the impact of peroxisome dysfunction, and the influence of early life trauma on health. The symposium speakers presented data from studies conducted in a variety of common laboratory animals as well as less-common species, including C. elegans, Drosophila, mice, rhesus macaques, elephants and humans. The consensus of the symposium speakers is that this consortium highlights the strength of aging research in the Midwestern United States as well as the benefits of a collaborative and diverse approach to geroscience.

[1]  N. LaRusso,et al.  An aged immune system drives senescence and ageing of solid organs , 2021, Nature.

[2]  M. Yandell,et al.  Elephant Genomes Reveal Accelerated Evolution in Mechanisms Underlying Disease Defenses , 2021, Molecular biology and evolution.

[3]  Deyang Yu,et al.  The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. , 2021, Cell metabolism.

[4]  Deyang Yu,et al.  Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice , 2020, Nature Aging.

[5]  G. Wong,et al.  Is exercise a senolytic medicine? A systematic review , 2020, Aging cell.

[6]  S. Kritchevsky,et al.  The Translational Geroscience Network: Supporting a New Paradigm to Alleviate Age-Related Chronic Disease , 2020, Innovation in Aging.

[7]  D. Baker,et al.  Cellular senescence in ageing: from mechanisms to therapeutic opportunities , 2020, Nature Reviews Molecular Cell Biology.

[8]  D. Lusseau,et al.  The effects of graded levels of calorie restriction: XVI. Metabolomic changes in the cerebellum indicate activation of hypothalamocerebellar connections driven by hunger responses. , 2020, The journals of gerontology. Series A, Biological sciences and medical sciences.

[9]  N. LeBrasseur,et al.  Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span. , 2020, Annual review of pharmacology and toxicology.

[10]  Brian R. Kotajarvi,et al.  The senescence-associated secretome as an indicator of age and medical risk. , 2020, JCI insight.

[11]  Maintaining a scientific community while social distancing , 2020, Translational Medicine of Aging.

[12]  M. Desco,et al.  T cells with dysfunctional mitochondria induce multimorbidity and premature senescence , 2020, Science.

[13]  R. de Cabo,et al.  Untangling Determinants of Enhanced Health and Lifespan through a Multi-omics Approach in Mice. , 2020, Cell metabolism.

[14]  S. Inouye,et al.  Delirium: a missing piece in the COVID-19 pandemic puzzle , 2020, Age and ageing.

[15]  L. Mao,et al.  Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. , 2020, JAMA neurology.

[16]  V. Prahlad,et al.  Global Transcriptome Changes That Accompany Alterations in Serotonin Levels in Caenorhabditis elegans , 2020, G3: Genes, Genomes, Genetics.

[17]  J. Weiner,et al.  Serotonin signaling by maternal neurons upon stress ensures progeny survival , 2020, bioRxiv.

[18]  R. de Cabo,et al.  A toolbox for the longitudinal assessment of healthspan in aging mice , 2020, Nature Protocols.

[19]  R. Colman,et al.  Molecular and Functional Networks Linked to Sarcopenia Prevention by Caloric Restriction in Rhesus Monkeys. , 2020, Cell systems.

[20]  V. Lummaa,et al.  Asian elephants exhibit post-reproductive lifespans , 2019, BMC Evolutionary Biology.

[21]  Andres Metspalu,et al.  A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals , 2019, Nature Communications.

[22]  S. Weinberg,et al.  Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function , 2019, Cell reports.

[23]  L. Partridge,et al.  Branched-chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control , 2019, Nature Metabolism.

[24]  D. Lusseau,et al.  The Effects of Graded Levels of Calorie Restriction: XIV. Global Metabolomics Screen Reveals Brown Adipose Tissue Changes in Amino Acids, Catecholamines, and Antioxidants After Short-Term Restriction in C57BL/6 Mice , 2019, The journals of gerontology. Series A, Biological sciences and medical sciences.

[25]  Evan Z. Macosko,et al.  Single‐Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell‐State Changes , 2019, Immunity.

[26]  R. de Cabo,et al.  Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories. , 2019, Cell metabolism.

[27]  M. Beibel,et al.  TORC1 inhibition enhances immune function and reduces infections in the elderly , 2018, Science Translational Medicine.

[28]  D. Allison,et al.  Senolytics Improve Physical Function and Increase Lifespan in Old Age , 2018, Nature Medicine.

[29]  Paul D Hutchins,et al.  Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys. , 2018, Cell metabolism.

[30]  B. Schumacher,et al.  DNA damage responses and p53 in the aging process. , 2018, Blood.

[31]  Peng-Yuan Yang,et al.  Sensing and Transmitting Intracellular Amino Acid Signals through Reversible Lysine Aminoacylations. , 2018, Cell metabolism.

[32]  S. A. Arriola Apelo,et al.  Restoration of metabolic health by decreased consumption of branched‐chain amino acids , 2017, The Journal of physiology.

[33]  C. Green,et al.  Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System. , 2017, Cell metabolism.

[34]  B. Winblad,et al.  The worldwide costs of dementia 2015 and comparisons with 2010 , 2017, Alzheimer's & Dementia.

[35]  R. Kohanski,et al.  Geroscience and the trans-NIH Geroscience Interest Group, GSIG , 2017, GeroScience.

[36]  S. A. Arriola Apelo,et al.  Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. , 2016, Cell reports.

[37]  C. Pieper,et al.  Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans , 2016, Aging.

[38]  L. Ferrucci,et al.  Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. , 2016, Cell metabolism.

[39]  R. de Cabo,et al.  Measures of Healthspan as Indices of Aging in Mice-A Recommendation. , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[40]  J. Rabinowitz,et al.  A branched chain amino acid metabolite drives vascular transport of fat and causes insulin resistance , 2016, Nature Medicine.

[41]  Shane T. Jensen,et al.  Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans. , 2015, JAMA.

[42]  Simon R. Goodyear,et al.  The effects of graded levels of calorie restriction: I. impact of short term calorie and protein restriction on body composition in the C57BL/6 mouse , 2015, Oncotarget.

[43]  J. Praestgaard,et al.  mTOR inhibition improves immune function in the elderly , 2014, Science Translational Medicine.

[44]  C. Semenkovich,et al.  Peroxisomes: a nexus for lipid metabolism and cellular signaling. , 2014, Cell metabolism.

[45]  Richard G Melvin,et al.  The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. , 2014, Cell metabolism.

[46]  M. Levine,et al.  Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. , 2014, Cell metabolism.

[47]  K. Langa,et al.  Functional disability, cognitive impairment, and depression after hospitalization for pneumonia. , 2013, The American journal of medicine.

[48]  C. Weyand,et al.  Understanding immunosenescence to improve responses to vaccines , 2013, Nature Immunology.

[49]  Paco Martorell,et al.  Monetary costs of dementia in the United States. , 2013, The New England journal of medicine.

[50]  K. Langa,et al.  Long-term cognitive impairment and functional disability among survivors of severe sepsis. , 2010, JAMA.

[51]  G. Bernard,et al.  Delirium as a predictor of long-term cognitive impairment in survivors of critical illness , 2010, Critical care medicine.

[52]  Linda Partridge,et al.  Extending Healthy Life Span—From Yeast to Humans , 2010, Science.

[53]  R. Weindruch,et al.  Metabolic reprogramming, caloric restriction and aging , 2010, Trends in Endocrinology & Metabolism.

[54]  D. van der A,et al.  Dietary Intake of Total, Animal, and Vegetable Protein and Risk of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL Study , 2009, Diabetes Care.

[55]  N. Sharpless,et al.  Expression of p16INK4a in peripheral blood T‐cells is a biomarker of human aging , 2009, Aging cell.

[56]  Y. Huang,et al.  Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1β and anti-inflammatory IL-10 cytokines , 2009, Brain, Behavior, and Immunity.

[57]  N. Larsson,et al.  Mitochondrial dysfunction as a cause of ageing , 2008, Journal of internal medicine.

[58]  Suresh I. S. Rattan,et al.  Hormesis in aging , 2008, Ageing Research Reviews.

[59]  R. Slotow,et al.  Modelling the effect of age-specific mortality on elephant Loxodonta africana populations: can natural mortality provide regulation? , 2008, Oryx.

[60]  B. McEwen,et al.  Microglia derived from aging mice exhibit an altered inflammatory profile , 2007, Glia.

[61]  Jing Chen,et al.  Exaggerated neuroinflammation and sickness behavior in aged mice after activation of the peripheral innate immune system , 2005 .

[62]  R. S. Sohal,et al.  Genotype and age influence the effect of caloric intake on mortality in mice , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[63]  M. Grabenbauer,et al.  Mitochondrial alterations caused by defective peroxisomal biogenesis in a mouse model for Zellweger syndrome (PEX5 knockout mouse). , 2001, The American journal of pathology.

[64]  J. Whitsett,et al.  GM-CSF regulates protein and lipid catabolism by alveolar macrophages. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[65]  C M McCay,et al.  The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. , 1935, Nutrition.

[66]  Denham Harman,et al.  The Biologic Clock: The Mitochondria? , 1972, Journal of the American Geriatrics Society.

[67]  L. Hayflick,et al.  The serial cultivation of human diploid cell strains. , 1961, Experimental cell research.