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https://www.readbyqxmd.com/read/28610949/calorie-restriction-in-rodents-caveats-to-consider
#1
REVIEW
Donald K Ingram, Rafael de Cabo
The calorie restriction paradigm has provided one of the most widely used and most useful tools for investigating mechanisms of aging and longevity. By far, rodent models have been employed most often in these endeavors. Over decades of investigation, claims have been made that the paradigm produces the most robust demonstration that aging is malleable. In the current review of the rodent literature, we present arguments that question the robustness of the paradigm to increase lifespan and healthspan. Specifically, there are several questions to consider as follows: (1) At what age does CR no longer produce benefits? (2) Does CR attenuate cognitive decline? (3) Are there negative effects of CR, including effects on bone health, wound healing, and response to infection? (4) How important is schedule of feeding? (5) How long does CR need to be imposed to be effective? (6) How do genotype and gender influence CR? (7) What role does dietary composition play? Consideration of these questions produce many caveats that should guide future investigations to move the field forward...
June 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28585366/advances-in-therapeutic-approaches-to-extend-healthspan-a-perspective-from-the-2-nd-scripps-symposium-on-the-biology-of-aging
#2
Paul D Robbins, Laura J Niedernhofer
The 2(nd) Scripps Florida Symposium on The Biology of Aging entitled 'Advances in Therapeutic Approaches to Extend Healthspan' was held on January 22(nd) -25(th) , 2017 at The Scripps Research Institute in Jupiter, Florida. The meeting highlighted a variety of therapeutic approaches in animal models of aging that either are or soon will be in clinic trials. For example, drugs targeting senescent cells, metformin, rapalogs, NAD precursors, young plasma, mitochondrial-targeted free radical scavengers, stem cells, and stem cell factors all have shown significant preclinical efficacy...
June 6, 2017: Aging Cell
https://www.readbyqxmd.com/read/28575157/sex-differences-in-aging-genomic-instability
#3
Kathleen E Fischer, Nicole C Riddle
Aging is characterized by decreasing physiological integration, reduced function, loss of resilience and increased risk of death. Paradoxically, although women live longer, they suffer greater morbidity particularly late in life. These sex differences in human lifespan and healthspan are consistently observed in all countries and during every era for which reliable data exist. While these differences are ubiquitous in humans, evidence of sex differences in longevity and health for other species is more equivocal...
June 2, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28559281/uridine-monophosphate-synthetase-enables-eukaryotic-de-novo-nad-biosynthesis-from-quinolinic-acid
#4
Melanie R McReynolds, Wenqing Wang, Lauren M Holleran, Wendy Hanna-Rose
NAD+ biosynthesis is an attractive and promising therapeutic target for influencing healthspan and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD+ biosynthetic pathways. Here we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD+ biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD+ biosynthetic pathway...
May 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28556428/identification-of-tissue-specific-transcriptional-markers-of-caloric-restriction-in-the-mouse-and-their-use-to-evaluate-caloric-restriction-mimetics
#5
Jamie L Barger, James M Vann, Nicole L Cray, Thomas D Pugh, Angela Mastaloudis, Shelly N Hester, Steven M Wood, Michael A Newton, Richard Weindruch, Tomas A Prolla
Caloric restriction (CR) without malnutrition has been shown to retard several aspects of the aging process and to extend lifespan in different species. There is strong interest in the identification of CR mimetics (CRMs), compounds that mimic the beneficial effects of CR on lifespan and healthspan without restriction of energy intake. Identification of CRMs in mammals is currently inefficient due to the lack of screening tools. We have performed whole-genome transcriptional profiling of CR in seven mouse strains (C3H/HeJ, CBA/J, DBA/2J, B6C3F1/J, 129S1/SvImJ, C57BL/6J, and BALB/cJ) in white adipose tissue (WAT), gastrocnemius muscle, heart, and brain neocortex...
May 26, 2017: Aging Cell
https://www.readbyqxmd.com/read/28552719/regulation-of-longevity-by-fgf21-interaction-between-energy-metabolism-and-stress-responses
#6
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses...
May 25, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28551577/bioactive-growth-hormone-in-older-men-and-women-it-s-relationship-to-immune-markers-and-healthspan
#7
William J Kraemer, Mary J Kennett, Andrea M Mastro, Roger J McCarter, Connie J Rogers, William H DuPont, Shawn D Flanagan, William J Turbitt, Maren S Fragala, Emily M Post, Wesley C Hymer
OBJECTIVE: The consequences of age-related decline in the somatotropic axis of humans are complex and remain largely unresolved. We tested the hypothesis that hGH measurements of plasma by bioassay vs immunoassay from samples obtained from free-living, elderly individuals would reveal a dichotomy in GH activities that are correlated with the functional status of the donors, i.e. their healthspan. DESIGN: Forty-one men and women of advanced age (men: N=16, age, 80...
June 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28498894/the-intersection-of-aging-biology-and-the-pathobiology-of-lung-diseases-a-joint-nhlbi-nia-workshop
#8
Gr Scott Budinger, Ronald A Kohanski, Weiniu Gan, Michael S Kobor, Luis A Amaral, Mary Armanios, Karl T Kelsey, Annie Pardo, Rubin Tuder, Fernando Macian, Navdeep Chandel, Douglas Vaughan, Mauricio Rojas, Ana L Mora, Elizabeth Kovacs, Steven R Duncan, Toren Finkel, Augustine Choi, Oliver Eickelberg, Danica Chen, Alvar Agusti, Moises Selman, William E Balch, Paula Busse, Anning Lin, Richard Morimoto, Jacob I Sznajder, Victor J Thannickal
Death from chronic lung disease is increasing and Chronic Obstructive Pulmonary Disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide population ages. Chronic lung diseases are associated with substantial morbidity, frequently resulting in exercise limiting dyspnea, immobilization and isolation. Therefore, effective strategies to prevent or treat lung disease are likely to increase healthspan as well as lifespan...
May 12, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28484723/interleukin-7-and-immunosenescence
#9
REVIEW
Vanloan Nguyen, Andrew Mendelsohn, James W Larrick
The age of an individual is an important, independent risk factor for many of the most common diseases afflicting modern societies. Interleukin-7 (IL-7) plays a central, critical role in the homeostasis of the immune system. Recent studies support a critical role for IL-7 in the maintenance of a vigorous healthspan. We describe the role of IL-7 and its receptor in immunosenescence, the aging of the immune system. An understanding of the role that IL-7 plays in aging may permit parsimonious preventative or therapeutic solutions for diverse conditions...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28471941/basic-science-and-pathogenesis-of-ageing-with-hiv-potential-mechanisms-and-biomarkers
#10
Claire Lagathu, Andrea Cossarizza, Véronique Béréziat, Milena Nasi, Jacqueline Capeau, Marcello Pinti
: The increased prevalence of age-related comorbidities and mortality is worrisome in ageing HIV-infected patients. Here, we aim to analyse the different ageing mechanisms with regard to HIV infection. Ageing results from the time-dependent accumulation of random cellular damage. Epigenetic modifications and mitochondrial DNA haplogroups modulate ageing. In antiretroviral treatment-controlled patients, epigenetic clock appears to be advanced, and some haplogroups are associated with HIV infection severity. Telomere shortening is enhanced in HIV-infected patients because of HIV and some nucleoside analogue reverse transcriptase inhibitors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28461251/mitophagy-and-age-related-pathologies-development-of-new-therapeutics-by-targeting-mitochondrial-turnover
#11
REVIEW
Konstantinos Palikaras, Ioanna Daskalaki, Maria Markaki, Nektarios Tavernarakis
Mitochondria are highly dynamic and semi-autonomous organelles, essential for many fundamental cellular processes, including energy production, metabolite synthesis, ion homeostasis, lipid metabolism and initiation of apoptotic cell death. Proper mitochondrial physiology is a prerequisite for health and survival. Generation of new and removal of damaged or unwanted mitochondria are tightly controlled processes that need to be accurately coordinated for the maintenance of mitochondrial and cellular homeostasis...
April 28, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28457986/metabolome-analysis-of-effect-of-aspirin-on-drosophila-lifespan-extension
#12
Chaochun Song, Chenxing Zhu, Qi Wu, Jiancheng Qi, Yue Gao, Zhichao Zhang, Uma Gaur, Deying Yang, Xiaolan Fan, Mingyao Yang
Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin-treated flies...
September 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28449241/autophagy-compensates-impaired-energy-metabolism-in-clpxp-deficient-podospora-anserina-strains-and-extends-healthspan
#13
Laura Knuppertz, Heinz D Osiewacz
The degradation of nonfunctional mitochondrial proteins is of fundamental relevance for maintenance of cellular homeostasis. The heteromeric CLPXP protein complex in the mitochondrial matrix is part of this process. In the fungal aging model Podospora anserina, ablation of CLPXP leads to an increase in healthy lifespan. Here, we report that this counterintuitive increase depends on a functional autophagy machinery. In PaClpXP mutants, autophagy is involved in energy conservation and the compensation of impairments in respiration...
April 27, 2017: Aging Cell
https://www.readbyqxmd.com/read/28448551/characterization-of-physiological-defects-in-adult-sirt6-mice
#14
Victoria Peshti, Alexey Obolensky, Liat Nahum, Yariv Kanfi, Moran Rathaus, Maytal Avraham, Simon Tinman, Fredrick W Alt, Eyal Banin, Haim Y Cohen
The NAD+-dependent SIRT6 deacetylase was shown to be a major regulator of lifespan and healthspan. Mice deficient for SIRT6 develop a premature aging phenotype and metabolic defects, and die before four weeks of age. Thus, the effect of SIRT6 deficiency in adult mice is unknown. Here we show that SIRT6-/- mice in mixed 129/SvJ/BALB/c background reach adulthood, allowing examination of SIRT6-related metabolic and developmental phenotypes in adult mice. In this mixed background, at 200 days of age, more than 80% of the female knock-out mice were alive whereas only 10% of male knock-out mice survived...
2017: PloS One
https://www.readbyqxmd.com/read/28447066/neuronal-functions-of-foxo-daf-16
#15
REVIEW
Sun Y Kim, Ashley E Webb
The FOXO family of transcription factors plays a conserved role in longevity and tissue homeostasis across species. In the mammalian nervous system, emerging evidence has implicated FOXOs in cognitive performance, stem cell maintenance, regeneration, and protection against stress. Much of what we know about neuronal functions of FOXO emerged from recent studies in C. elegans. Similar to mammalian FOXO, the worm FOXO ortholog, called DAF-16, regulates learning and memory, regeneration, and stress resistance in neurons...
March 31, 2017: Nutrition and Healthy Aging
https://www.readbyqxmd.com/read/28427536/health-risks-of-food-oxidation
#16
Mario Estévez, Zhuqing Li, Olugbenga P Soladoye, Thomas Van-Hecke
The impact of dietary habits on our health is indisputable. Consumer's concern on aging and age-related diseases challenges scientists to underline the potential role of food on the extension and guarantee of lifespan and healthspan. While some dietary components and habits are generally regarded as beneficial for our health, some others are being found to exert potential toxic effects and hence, contribute to the onset of particular health disorders. Among the latter, lipid and protein oxidation products formed during food production, storage, processing, and culinary preparation have been recently identified as potentially harmful to humans...
2017: Advances in Food and Nutrition Research
https://www.readbyqxmd.com/read/28425851/altered-structure-and-function-of-adipose-tissue-in-long-lived-mice-with-growth-hormone-related-mutations
#17
Justin Darcy, Samuel McFadden, Andrzej Bartke
A major focus of biogerontology is elucidating the role(s) of the endocrine system in aging and the accumulation of age-related diseases. Endocrine control of mammalian longevity was first reported in Ames dwarf (Prop1(df)) mice, which are long-lived due to a recessive Prop1 loss-of-function mutation resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone, and prolactin. Following this report, several other GH-related mutants with altered longevity have been described including long-lived Snell dwarf and growth hormone receptor knockout mice, and short-lived GH overexpressing transgenic mice...
April 3, 2017: Adipocyte
https://www.readbyqxmd.com/read/28409331/igf-1-has-sexually-dimorphic-pleiotropic-and-time-dependent-effects-on-healthspan-pathology-and-lifespan
#18
Nicole M Ashpole, Sreemathi Logan, Andriy Yabluchanskiy, Matthew C Mitschelen, Han Yan, Julie A Farley, Erik L Hodges, Zoltan Ungvari, Anna Csiszar, Sixia Chen, Constantin Georgescu, Gene B Hubbard, Yuji Ikeno, William E Sonntag
Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated...
April 2017: GeroScience
https://www.readbyqxmd.com/read/28401731/impact-of-early-personal-history-characteristics-on-the-pace-of-aging-implications-for-clinical-trials-of-therapies-to-slow-aging-and-extend-healthspan
#19
Daniel W Belsky, Avshalom Caspi, Harvey J Cohen, William E Kraus, Sandhya Ramrakha, Richie Poulton, Terrie E Moffitt
Therapies to extend healthspan are poised to move from laboratory animal models to human clinical trials. Translation from mouse to human will entail challenges, among them the multifactorial heterogeneity of human aging. To inform clinical trials about this heterogeneity, we report how humans' pace of biological aging relates to personal-history characteristics. Because geroprotective therapies must be delivered by midlife to prevent age-related disease onset, we studied young-adult members of the Dunedin Study 1972-73 birth cohort (n = 954)...
April 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/28401650/caenorhabditis-elegans-orthologs-of-human-genes-differentially-expressed-with-age-are-enriched-for-determinants-of-longevity
#20
George L Sutphin, Grant Backer, Susan Sheehan, Shannon Bean, Caroline Corban, Teresa Liu, Marjolein J Peters, Joyce B J van Meurs, Joanne M Murabito, Andrew D Johnson, Ron Korstanje
We report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes selected based on orthology to human genes differentially expressed with age. We find substantial enrichment in genes for which knockdown increased lifespan. This enrichment is markedly higher than published genomewide longevity screens in C. elegans and similar to screens that preselected candidates based on longevity-correlated metrics (e.g., stress resistance). Of the 50 genes that affected lifespan, 46 were previously unreported...
April 12, 2017: Aging Cell
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