Aging and energetics’ ‘Top 40’ future research opportunities 2010-2013

Background: As part of a coordinated effort to expand our research activity at the interface of Aging and Energetics a team of investigators at The University of Alabama at Birmingham systematically assayed and catalogued the top research priorities identified in leading publications in that domain, believing the result would be useful to the scientific community at large. Objective: To identify research priorities and opportunities in the domain of aging and energetics as advocated in the 40 most cited papers related to aging and energetics in the last 4 years. Design: The investigators conducted a search for papers on aging and energetics in Scopus, ranked the resulting papers by number of times they were cited, and selected the ten most-cited papers in each of the four years that include 2010 to 2013, inclusive. Results: Ten research categories were identified from the 40 papers. These included: (1) Calorie restriction (CR) longevity response, (2) role of mTOR (mechanistic target of Rapamycin) and related factors in lifespan extension, (3) nutrient effects beyond energy (especially resveratrol, omega-3 fatty acids, and selected amino acids), 4) autophagy and increased longevity and health, (5) aging-associated predictors of chronic disease, (6) use and effects of mesenchymal stem cells (MSCs), (7) telomeres relative to aging and energetics, (8) accretion and effects of body fat, (9) the aging heart, and (10) mitochondria, reactive oxygen species, and cellular energetics. Conclusion: The field is rich with exciting opportunities to build upon our existing knowledge about the relations among aspects of aging and aspects of energetics and to better understand the mechanisms which connect them.

[1]  Caroline Tao,et al.  Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. , 2014, Cell metabolism.

[2]  Degui Zhi,et al.  The Bioenergetic Health Index: a new concept in mitochondrial translational research , 2014, Clinical science.

[3]  G. Kroemer,et al.  Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification , 2014, PLoS genetics.

[4]  Jianhua Zhang,et al.  Redox regulation of antioxidants, autophagy, and the response to stress: Implications for electrophile therapeutics , 2014, Free radical biology & medicine.

[5]  G. Juhász,et al.  Nucleocytosolic Depletion of the Energy Metabolite Acetyl-Coenzyme A Stimulates Autophagy and Prolongs Lifespan , 2014, Cell metabolism.

[6]  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.

[7]  S. Austad,et al.  Rapamycin extends life and health in C57BL/6 mice. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[8]  F. Booth,et al.  Combining metformin and aerobic exercise training in the treatment of type 2 diabetes and NAFLD in OLETF rats. , 2014, American journal of physiology. Endocrinology and metabolism.

[9]  W. Burhans,et al.  Reactive oxygen species, ageing and the hormesis police. , 2014, FEMS yeast research.

[10]  Philip A. Kramer,et al.  A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: Implications for their use as bioenergetic biomarkers , 2014, Redox biology.

[11]  Jianhua Zhang,et al.  Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease , 2013, Redox biology.

[12]  Brady Olsen,et al.  Molecular mechanisms underlying genotype‐dependent responses to dietary restriction , 2013, Aging cell.

[13]  S. Ballinger,et al.  Mitochondrial genetics and obesity: evolutionary adaptation and contemporary disease susceptibility. , 2013, Free radical biology & medicine.

[14]  S. Ballinger,et al.  Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload. , 2013, The Biochemical journal.

[15]  Jianhua Zhang,et al.  Cellular metabolic and autophagic pathways: traffic control by redox signaling. , 2013, Free radical biology & medicine.

[16]  P. Kapahi,et al.  High carbohydrate–low protein consumption maximizes Drosophila lifespan , 2013, Experimental Gerontology.

[17]  J. Pyo,et al.  Overexpression of Atg5 in mice activates autophagy and extends lifespan , 2013, Nature Communications.

[18]  R. Nixon,et al.  The role of autophagy in neurodegenerative disease , 2013, Nature Medicine.

[19]  T. Prolla,et al.  Dysregulation of Mitochondrial Quality Control Processes Contribute to Sarcopenia in a Mouse Model of Premature Aging , 2013, PloS one.

[20]  Robert W. Williams,et al.  Mitonuclear protein imbalance as a conserved longevity mechanism , 2013, Nature.

[21]  M. Platzer,et al.  Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension. , 2013, Molecular metabolism.

[22]  Philip A. Kramer,et al.  Methods for defining distinct bioenergetic profiles in platelets, lymphocytes, monocytes, and neutrophils, and the oxidative burst from human blood , 2013, Laboratory Investigation.

[23]  R. Kineman,et al.  Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity? , 2013, The Journal of endocrinology.

[24]  T. Kadowaki,et al.  Adiponectin receptor as a key player in healthy longevity and obesity-related diseases. , 2013, Cell metabolism.

[25]  S. Ballinger,et al.  Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics. , 2013, Biochemical Society transactions.

[26]  E. Benjamin,et al.  Electrocardiographic PR Interval and Adverse Outcomes in Older Adults: The Health, Aging, and Body Composition Study , 2013, Circulation. Arrhythmia and electrophysiology.

[27]  J. Graff,et al.  Adenosine nucleotide biosynthesis and AMPK regulate adult life span and mediate the longevity benefit of caloric restriction in flies. , 2013, Cell metabolism.

[28]  J. Mitchell,et al.  Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR. , 2013, The Biochemical journal.

[29]  J. Lancaster,et al.  Integration of cellular bioenergetics with mitochondrial quality control and autophagy , 2012, Biological chemistry.

[30]  T. Shioi,et al.  Aging as a substrate of heart failure. , 2012, Journal of cardiology.

[31]  David B. Allison,et al.  Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study , 2012, Nature.

[32]  F. Booth,et al.  Physical activity opposes coronary vascular dysfunction induced during high fat feeding in mice , 2012, The Journal of physiology.

[33]  D. Rubinsztein,et al.  Autophagy modulation as a potential therapeutic target for diverse diseases , 2012, Nature Reviews Drug Discovery.

[34]  F. Booth,et al.  Integrative and Translational Physiology : Integrative Aspects of Energy Homeostasis and Metabolic Diseases Potential clinical translation of juvenile rodent inactivity models to study the onset of childhood obesity , 2012 .

[35]  Shinichi Nakagawa,et al.  The effect of resveratrol on longevity across species: a meta-analysis , 2012, Biology Letters.

[36]  M. Blasco,et al.  Beyond average: potential for measurement of short telomeres , 2012, Aging.

[37]  C. Annweiler,et al.  Nutrient Biomarker Patterns, Cognitive Function, and Mri Measures of Brain Aging , 2012, Neurology.

[38]  W. Swindell Dietary restriction in rats and mice: A meta-analysis and review of the evidence for genotype-dependent effects on lifespan , 2012, Ageing Research Reviews.

[39]  A. Benetos,et al.  “Is obesity linked to aging?” Adipose tissue and the role of telomeres , 2012, Ageing Research Reviews.

[40]  Dudley Lamming,et al.  Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity , 2012, Science.

[41]  R. Weindruch,et al.  The caloric restriction paradigm: Implications for healthy human aging , 2012, American journal of human biology : the official journal of the Human Biology Council.

[42]  J. Handa,et al.  Glycation‐altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age‐related disease (in nondiabetics) , 2012, Aging cell.

[43]  Y. Lu,et al.  Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. , 2012, Bone.

[44]  E. Napoli,et al.  Evaluation of senescence in mesenchymal stem cells isolated from equine bone marrow, adipose tissue, and umbilical cord tissue. , 2012, Stem cells and development.

[45]  Jürgen Bereiter-Hahn,et al.  Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan , 2012, Autophagy.

[46]  T. Buder,et al.  Aging Changes of the Midfacial Fat Compartments: A Computed Tomographic Study , 2012, Plastic and reconstructive surgery.

[47]  Jianhua Zhang,et al.  Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling , 2011, The Biochemical journal.

[48]  J. Kaye,et al.  Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging , 2011, Neurology.

[49]  Edward G Lakatta,et al.  Aging-associated cardiovascular changes and their relationship to heart failure. , 2012, Heart failure clinics.

[50]  V. Conti,et al.  Role of sirtuins, calorie restriction and physical activity in aging. , 2012, Frontiers in bioscience.

[51]  E. Dazert,et al.  mTOR signaling in disease. , 2011, Current opinion in cell biology.

[52]  R. Bloomer,et al.  Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings , 2011, Nutrition journal.

[53]  Mark T Gladwin,et al.  Oxidases and peroxidases in cardiovascular and lung disease: new concepts in reactive oxygen species signaling. , 2011, Free radical biology & medicine.

[54]  D. Rubinsztein,et al.  Autophagy and Aging , 2011, Cell.

[55]  Alexander M. Wolf,et al.  Caloric Restriction Primes Mitochondria for Ischemic Stress by Deacetylating Specific Mitochondrial Proteins of the Electron Transport Chain , 2011, Circulation research.

[56]  Chen-Yu Liao,et al.  Fat maintenance is a predictor of the murine lifespan response to dietary restriction , 2011, Aging cell.

[57]  S. Rubin,et al.  Cumulative Inflammatory Load Is Associated with Short Leukocyte Telomere Length in the Health, Aging and Body Composition Study , 2011, PloS one.

[58]  L. Partridge,et al.  A longer and healthier life with TOR down-regulation: genetics and drugs. , 2011, Biochemical Society transactions.

[59]  A. Boyle,et al.  The aging heart and post-infarction left ventricular remodeling. , 2011, Journal of the American College of Cardiology.

[60]  E. Greer,et al.  The Genetic Network of Life-Span Extension by Dietary Restriction , 2011 .

[61]  J. Kemnitz Calorie restriction and aging in nonhuman primates. , 2011, ILAR journal.

[62]  M. Mattson,et al.  Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. , 2010, Antioxidants & redox signaling.

[63]  M. Jensen,et al.  Fat tissue, aging, and cellular senescence , 2010, Aging cell.

[64]  Chen-Yu Liao,et al.  Genetic dissection of dietary restriction in mice supports the metabolic efficiency model of life extension , 2010, Experimental Gerontology.

[65]  Nektarios Tavernarakis,et al.  Can autophagy promote longevity? , 2010, Nature Cell Biology.

[66]  A. Fodor,et al.  Strain screen and haplotype association mapping of wheel running in inbred mouse strains. , 2010, Journal of applied physiology.

[67]  W. Burhans,et al.  Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H2O2 and superoxide dismutase activity , 2010, Proceedings of the National Academy of Sciences.

[68]  A. Reichert,et al.  Impaired quality control of mitochondria: Aging from a new perspective , 2010, Experimental Gerontology.

[69]  Robert W. Williams,et al.  Metabolic Networks of Longevity , 2010, Cell.

[70]  F. Kronenberg,et al.  Telomere length and risk of incident cancer and cancer mortality. , 2010, JAMA.

[71]  Di Chen,et al.  With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. , 2010, Cell metabolism.

[72]  Yongmei Liu,et al.  Inflammatory Markers and Incident Heart Failure Risk in Older Adults: The Health, Aging, and Body Composition Study , 2009 .

[73]  R. Sellers,et al.  Pathophysiology of Cyclooxygenases in Cardiovascular Homeostasis , 2010, Veterinary pathology.

[74]  A. Salmon,et al.  Update on the oxidative stress theory of aging: does oxidative stress play a role in aging or healthy aging? , 2010, Free radical biology & medicine.

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

[76]  M. Blagosklonny Calorie restriction: Decelerating mTOR-driven aging from cells to organisms (including humans) , 2010, Cell cycle.

[77]  Chen-Yu Liao,et al.  Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening , 2010, Aging cell.

[78]  C. Leeuwenburgh,et al.  Skeletal muscle autophagy and apoptosis during aging: Effects of calorie restriction and life-long exercise , 2010, Experimental Gerontology.

[79]  M. Zamboni,et al.  Aging and Regional Differences in Fat Cell Progenitors – A Mini-Review , 2010, Gerontology.

[80]  Nektarios Tavernarakis,et al.  Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy , 2010, Cell Death and Disease.

[81]  Yan Li,et al.  Mice deficient in both Mn superoxide dismutase and glutathione peroxidase-1 have increased oxidative damage and a greater incidence of pathology but no reduction in longevity. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[82]  Linda Partridge,et al.  Amino acid imbalance explains extension of lifespan by dietary restriction in Drosophila , 2009, Nature.

[83]  A. Bokov,et al.  Is the oxidative stress theory of aging dead? , 2009, Biochimica et biophysica acta.

[84]  Robert Ross,et al.  Age-related changes in total and regional fat distribution , 2009, Ageing Research Reviews.

[85]  Tibor Vellai,et al.  The regulation of aging: does autophagy underlie longevity? , 2009, Trends in cell biology.

[86]  P. Treuting,et al.  Lifespan extension in genetically modified mice , 2009, Aging cell.

[87]  Marco Pahor,et al.  Rapamycin fed late in life extends lifespan in genetically heterogeneous mice , 2009, Nature.

[88]  R. Nussbaum,et al.  Parkinson Phenotype in Aged PINK1-Deficient Mice Is Accompanied by Progressive Mitochondrial Dysfunction in Absence of Neurodegeneration , 2009, PloS one.

[89]  Yasuo Ohashi,et al.  Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. , 2009, JAMA.

[90]  M. Komatsu,et al.  Mitochondrial dysfunction and oxidative stress mediate the physiological impairment induced by the disruption of autophagy , 2009, Aging.

[91]  N. Barzilai,et al.  Biological approaches to mechanistically understand the healthy life span extension achieved by calorie restriction and modulation of hormones. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[92]  Michael P. Murphy,et al.  How mitochondria produce reactive oxygen species , 2008, The Biochemical journal.

[93]  C. Epstein,et al.  The overexpression of major antioxidant enzymes does not extend the lifespan of mice , 2008, Aging cell.

[94]  T. Vellai Autophagy genes and ageing , 2009, Cell Death and Differentiation.

[95]  Abraham Aviv,et al.  The epidemiology of human telomeres: faults and promises. , 2008, The journals of gerontology. Series A, Biological sciences and medical sciences.

[96]  Jie Shen,et al.  Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress , 2008, Proceedings of the National Academy of Sciences.

[97]  N. Barzilai,et al.  Visceral adipose tissue modulates mammalian longevity , 2008, Aging cell.

[98]  G. Taffet,et al.  Aging-related defects are associated with adverse cardiac remodeling in a mouse model of reperfused myocardial infarction. , 2008, Journal of the American College of Cardiology.

[99]  M. Kaeberlein,et al.  Dietary restriction by bacterial deprivation increases life span in wild-derived nematodes , 2008, Experimental Gerontology.

[100]  Daniel J. Klionsky,et al.  Autophagy fights disease through cellular self-digestion , 2008, Nature.

[101]  T. Vellai,et al.  Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans , 2008, Autophagy.

[102]  T. P. Neufeld,et al.  Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. , 2007, Genes & development.

[103]  S. Moncada,et al.  Nitric oxide and mitochondrial signaling: from physiology to pathophysiology. , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[104]  G. Shulman,et al.  Obesity-associated improvements in metabolic profile through expansion of adipose tissue. , 2007, The Journal of clinical investigation.

[105]  M. Stumvoll,et al.  Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. , 2007, The Journal of clinical endocrinology and metabolism.

[106]  S. Pletcher,et al.  Regulation of Drosophila Life Span by Olfaction and Food-Derived Odors , 2007, Science.

[107]  R. Kronmal,et al.  Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. , 2006, American journal of epidemiology.

[108]  S. Austad,et al.  Does caloric restriction extend life in wild mice? , 2006, Aging cell.

[109]  M. Beal,et al.  Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases , 2006, Nature.

[110]  R. DePinho,et al.  Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a , 2006, Nature.

[111]  M. Mattson,et al.  Ageing and neuronal vulnerability , 2006, Nature Reviews Neuroscience.

[112]  S. Moncada,et al.  The discovery of nitric oxide and its role in vascular biology , 2006, British journal of pharmacology.

[113]  T. Vellai,et al.  Inactivation of the Autophagy Gene bec-1 Triggers Apoptotic Cell Death in C. elegans , 2005, Current Biology.

[114]  M. Emond,et al.  Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria , 2005, Science.

[115]  A. Aviv,et al.  Rise in Insulin Resistance Is Associated With Escalated Telomere Attrition , 2005, Circulation.

[116]  Merry L Lindsey,et al.  Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function. , 2005, Cardiovascular research.

[117]  M. Smith-Wheelock,et al.  Methionine‐deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF‐I and insulin levels, and increases hepatocyte MIF levels and stress resistance , 2005, Aging cell.

[118]  A. Serretti,et al.  Genetics and drugs. , 2007, FDA consumer.

[119]  K. Davies,et al.  Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and 'aggresomes' during oxidative stress, aging, and disease. , 2004, The international journal of biochemistry & cell biology.

[120]  N. Avadhani,et al.  Mitochondrial signaling: the retrograde response. , 2004, Molecular cell.

[121]  J. McMurray,et al.  Targeted Anticytokine Therapy in Patients With Chronic Heart Failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL) , 2004, Circulation.

[122]  E. Lakatta Age-associated Cardiovascular Changes in Health: Impact on Cardiovascular Disease in Older Persons , 2004, Heart Failure Reviews.

[123]  C. Epstein,et al.  Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. , 2003, Physiological genomics.

[124]  Edward J Masoro,et al.  Subfield history: caloric restriction, slowing aging, and extending life. , 2003, Science of aging knowledge environment : SAGE KE.

[125]  Linda Partridge,et al.  Life history response of Mediterranean fruit flies to dietary restriction , 2002, Aging cell.

[126]  Xiao Man Yang,et al.  Aging is associated with resistance to effects of leptin on fat distribution and insulin action. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[127]  Xiao Man Yang,et al.  Leptin resistance during aging is independent of fat mass. , 2002, Diabetes.

[128]  P. Wilson,et al.  Obesity, diabetes, and risk of cardiovascular disease in the elderly. , 2002, The American journal of geriatric cardiology.

[129]  N. Holbrook,et al.  Oxidants, oxidative stress and the biology of ageing , 2000, Nature.

[130]  J. Kampert,et al.  Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. , 1999, JAMA.

[131]  Wei Chen,et al.  Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat. , 1998, The Journal of clinical investigation.

[132]  J. A. Zimmerman,et al.  Low methionine ingestion by rats extends life span. , 1993, The Journal of nutrition.

[133]  Edward L. Schneider,et al.  Handbook of the Biology of Aging , 1990 .

[134]  Richard Weindruch,et al.  The Retardation of Aging and Disease by Dietary Restriction , 1988 .

[135]  P. Segall,et al.  Low tryptophan diets delay reproductive aging , 1983, Mechanisms of Ageing and Development.

[136]  R Roberts,et al.  Deleterious effects of methylprednisolone in patients with myocardial infarction. , 1976, Circulation.

[137]  T. B. Osborne,et al.  THE EFFECT OF RETARDATION OF GROWTH UPON THE BREEDING PERIOD AND DURATION OF LIFE OF RATS. , 1917, Science.