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GeroScience

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https://www.readbyqxmd.com/read/30374935/report-nia-workshop-on-translating-genetic-variants-associated-with-longevity-into-drug-targets
#1
Nicholas J Schork, Nalini Raghavachari
To date, candidate gene and genome-wide association studies (GWAS) have led to the discovery of longevity-associated variants (LAVs) in genes such as FOXO3A and APOE. Unfortunately, translating variants into drug targets is challenging for any trait, and longevity is no exception. Interdisciplinary and integrative multi-omics approaches are needed to understand how LAVs affect longevity-related phenotypes at the molecular physiologic level in order to leverage their discovery to identify new drug targets. The NIA convened a workshop in August 2017 on emerging and novel in silico (i...
October 29, 2018: GeroScience
https://www.readbyqxmd.com/read/30345481/pacap-deficiency-as-a-model-of-aging
#2
REVIEW
D Reglodi, T Atlasz, E Szabo, A Jungling, A Tamas, T Juhasz, B D Fulop, A Bardosi
Dysregulation of neuropeptides may play an important role in aging-induced impairments. In the long list of neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) represents a highly effective cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. PACAP has neuro- and general cytoprotective effects due to anti-apoptotic, anti-inflammatory, and antioxidant actions. As PACAP is also a part of the endogenous protective machinery, it can be hypothesized that the decreased protective effects in lack of endogenous PACAP would accelerate age-related degeneration and PACAP knockout mice would display age-related degenerative signs earlier...
October 22, 2018: GeroScience
https://www.readbyqxmd.com/read/30338417/meta-analysis-identifies-mitochondrial-dna-sequence-variants-associated-with-walking-speed
#3
Todd M Manini, Thomas W Buford, John A Kairalla, Mary M McDermott, Carlos A Vaz Fragoso, Roger A Fielding, Fang-Chi Hsu, Neil Johannsen, Stephen Kritchevsky, Tamara B Harris, Anne B Newman, Steven R Cummings, Abby C King, Marco Pahor, Adam J Santanasto, Gregory J Tranah
Declines in walking speed are associated with a variety of poor health outcomes including disability, comorbidity, and mortality. While genetic factors are putative contributors to variability in walking, few genetic loci have been identified for this trait. We examined the role of mitochondrial genomic variation on walking speed by sequencing the entire mitochondrial DNA (mtDNA). Data were meta-analyzed from 1758 Lifestyle Interventions and Independence for Elders (LIFE) Study and replication data from 730 Health, Aging, and Body Composition (HABC) Study participants with baseline walking speed information...
October 18, 2018: GeroScience
https://www.readbyqxmd.com/read/30288646/repeated-valsalva-maneuvers-promote-symptomatic-manifestations-of-cerebral-microhemorrhages-implications-for-the-pathogenesis-of-vascular-cognitive-impairment-in-older-adults
#4
Zoltan Ungvari, Andriy Yabluchanskiy, Stefano Tarantini, Peter Toth, Angelia C Kirkpatrick, Anna Csiszar, Calin I Prodan
Multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds"), which are associated with rupture of small intracerebral vessels, have been recognized as an important cause for cognitive decline in older adults. Although recent studies demonstrate that CMHs are highly prevalent in patients 65 and older, many aspects of the pathogenesis and clinical significance of CMHs remain obscure. In this longitudinal observational study, a case of a 77-year-old man with multifocal CMHs is described, in whom the rupture of intracerebral vessels could be linked to repeatedly performing extended Valsalva maneuvers...
October 4, 2018: GeroScience
https://www.readbyqxmd.com/read/30151729/a-framework-for-selection-of-blood-based-biomarkers-for-geroscience-guided-clinical-trials-report-from-the-tame-biomarkers-workgroup
#5
REVIEW
Jamie N Justice, Luigi Ferrucci, Anne B Newman, Vanita R Aroda, Judy L Bahnson, Jasmin Divers, Mark A Espeland, Santica Marcovina, Michael N Pollak, Stephen B Kritchevsky, Nir Barzilai, George A Kuchel
Recent advances indicate that biological aging is a potentially modifiable driver of late-life function and chronic disease and have led to the development of geroscience-guided therapeutic trials such as TAME (Targeting Aging with MEtformin). TAME is a proposed randomized clinical trial using metformin to affect molecular aging pathways to slow the incidence of age-related multi-morbidity and functional decline. In trials focusing on clinical end-points (e.g., disease diagnosis or death), biomarkers help show that the intervention is affecting the underlying aging biology before sufficient clinical events have accumulated to test the study hypothesis...
August 27, 2018: GeroScience
https://www.readbyqxmd.com/read/30136078/dna-methylation-associated-with-healthy-aging-of-elderly-twins
#6
Sangkyu Kim, Jennifer Wyckoff, Anne-T Morris, Annemarie Succop, Ally Avery, Glen E Duncan, S Michal Jazwinski
Variation in healthy aging and lifespan is ascribed more to various non-genetic factors than to inherited genetic determinants, and a major goal in aging research is to reveal the epigenetic basis of aging. One approach to this goal is to find genomic sites or regions where DNA methylation correlates with biological age. Using health data from 134 elderly twins, we calculated a frailty index as a quantitative indicator of biological age, and by applying the Infinium HumanMethylation450K BeadChip technology to their leukocyte DNA samples, we obtained quantitative DNA methylation data on genome-wide CpG sites...
August 22, 2018: GeroScience
https://www.readbyqxmd.com/read/30121784/thioredoxin-overexpression-in-both-the-cytosol-and-mitochondria-accelerates-age-related-disease-and-shortens-lifespan-in-male-c57bl-6-mice
#7
Geneva M Cunningham, Lisa C Flores, Madeline G Roman, Christie Cheng, Sara Dube, Colton Allen, Joseph M Valentine, Gene B Hubbard, Yidong Bai, Thomas L Saunders, Yuji Ikeno
To investigate the role of increased levels of thioredoxin (Trx) in both the cytosol (Trx1) and mitochondria (Trx2) on aging, we have conducted a study to examine survival and age-related diseases using male mice overexpressing Trx1 and Trx2 (TXNTg × TXN2Tg). Our study demonstrated that the upregulation of Trx in both the cytosol and mitochondria in male TXNTg × TXN2Tg C57BL/6 mice resulted in a significantly shorter lifespan compared to wild-type (WT) mice. Cross-sectional pathology data showed a slightly higher incidence of neoplastic diseases in TXNTg × TXN2Tg mice than WT mice...
August 18, 2018: GeroScience
https://www.readbyqxmd.com/read/30143938/selected-abstracts-from-the-american-aging-association-47th-annual-meeting-improving-resilience-to-delay-aging-philadelphia-2018
#8
(no author information available yet)
No abstract text is available yet for this article.
August 2018: GeroScience
https://www.readbyqxmd.com/read/30099673/effects-of-long-term-dietary-administration-of-estrogen-receptor-beta-agonist-diarylpropionitrile-on-ovariectomized-female-icr-cd-1-mice
#9
Sherry A Said, Rachel Isedowo, Christilynn Guerin, Navreek N Nar, Leesa Lillie, Shawn Bukovac, Jonathan J Simone, Matthew R Green, Cheryl M McCormick, Jeffrey A Stuart
Diarylpropionitrile (DPN) is an estrogen receptor-β-specific agonist that has been linked to neuroprotection, preserving cognitive function with age, the suppression of anxiety-like behaviors, inhibition of cancer growth, and other positive properties. We hypothesized that DPN may have pro-longevity properties. DPN was administered via feed at a dose corresponding to approximately 3 mg/kg/day to ovariectomized female mice beginning at 7 months of age. Mice were followed for the duration of their lifespans while monitoring body mass, aspects of behavior, learning, memory, and frailty...
August 2018: GeroScience
https://www.readbyqxmd.com/read/30088182/the-high-degree-of-cystathionine-%C3%AE-synthase-cbs-activation-by-s-adenosylmethionine-sam-may-explain-naked-mole-rat-s-distinct-methionine-metabolite-profile-compared-to-mouse
#10
LETTER
https://www.readbyqxmd.com/read/30084059/how-healthy-is-the-healthspan-concept
#11
EDITORIAL
Matt Kaeberlein
No abstract text is available yet for this article.
August 2018: GeroScience
https://www.readbyqxmd.com/read/30074132/a-novel-high-throughput-assay-for-respiration-in-isolated-brain-microvessels-reveals-impaired-mitochondrial-function-in-the-aged-mice
#12
Venkata N Sure, Siva S V P Sakamuri, Jared A Sperling, Wesley R Evans, Ivan Merdzo, Ricardo Mostany, Walter L Murfee, David W Busija, Prasad V G Katakam
Cerebral blood flow (CBF) is uniquely regulated by the anatomical design of the cerebral vasculature as well as through neurovascular coupling. The process of directing the CBF to meet the energy demands of neuronal activity is referred to as neurovascular coupling. Microvasculature in the brain constitutes the critical component of the neurovascular coupling. Mitochondria provide the majority of ATP to meet the high-energy demand of the brain. Impairment of mitochondrial function plays a central role in several age-related diseases such as hypertension, ischemic brain injury, Alzheimer's disease, and Parkinson disease...
August 2018: GeroScience
https://www.readbyqxmd.com/read/30054861/a-pyridoindole-antioxidant-sme1ec2-regulates-contractility-relaxation-ability-cation-channel-activity-and-protein-carbonyl-modifications-in-the-aorta-of-young-and-old-rats-with-or-without-diabetes-mellitus
#13
Arzu Şakul, Nuray Arı, Ruzenna Sotnikova, Gülgün Ozansoy, Çimen Karasu
We studied the effects of treatment with SMe1EC, a hexahydropyridoindole antioxidant, on vascular reactivity, endothelial function, and oxidonitrosative stress level of thoracic aorta in young and old rats with or without diabetes mellitus. The rats were grouped as young control (YC 3 months old), old control (OC 15 months old), young diabetic (YD), old diabetic (OD), young control treated (YCT), old control treated (OCT), young diabetic treated (YDT), and old diabetic treated (ODT). Diabetes was induced by streptozotocin injection and subsequently SMe1EC2 (10 mg/kg/day, p...
August 2018: GeroScience
https://www.readbyqxmd.com/read/29934733/the-association-between-relevant-comorbidities-and-dementia-in-patients-with-atrial-fibrillation
#14
Per Wändell, Axel C Carlsson, Jan Sundquist, Kristina Sundquist
Risk of dementia is increased in patients with atrial fibrillation (AF). We aimed to study associations between relevant comorbidities and prevalent as well as incident dementia in AF patients. Study population included all adults (n = 12,283) ≥ 45 years diagnosed with AF at 75 primary care centers in Sweden 2001-2007. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (95% CI) for associations between comorbidities and prevalent dementia. In a subsample (n = 12,096), (excluding patients with dementia diagnosed before AF onset), Cox regression was used to estimate hazard ratios (HR) with 95% CIs for association between comorbidities, and incident dementia, after adjustment for age, socioeconomic factors and anticoagulant treatment...
June 22, 2018: GeroScience
https://www.readbyqxmd.com/read/29931650/rapamycin-increases-oxidative-metabolism-and-enhances-metabolic-flexibility-in-human-cardiac-fibroblasts
#15
Timothy Nacarelli, Ashley Azar, Oya Altinok, Zulfiya Orynbayeva, Christian Sell
Inhibition of mTOR signaling using rapamycin has been shown to increase lifespan and healthspan in multiple model organisms; however, the precise mechanisms for the beneficial effects of rapamycin remain uncertain. We have previously reported that rapamycin delays senescence in human cells and that enhanced mitochondrial biogenesis and protection from mitochondrial stress is one component of the benefit provided by rapamycin treatment. Here, using two models of senescence, replicative senescence and senescence induced by the presence of the Hutchinson-Gilford progeria lamin A mutation, we report that senescence is accompanied by elevated glycolysis and increased oxidative phosphorylation, which are both reduced by rapamycin...
June 21, 2018: GeroScience
https://www.readbyqxmd.com/read/29916025/short-term-weight-loss-reverses-obesity-induced-microvascular-endothelial-dysfunction
#16
Tamas Csipo, Gabor A Fulop, Agnes Lipecz, Stefano Tarantini, Tamas Kiss, Priya Balasubramanian, Anna Csiszar, Zoltan Ungvari, Andriy Yabluchanskiy
Obesity is one of the major risk factors for cardiovascular diseases and its prevalence is increasing in all age groups, with the biggest impact observed in middle-aged and older adults. A critical mechanism by which obesity promotes vascular pathologies in these patients involves impairment of endothelial function. While endothelial dysfunction in large vessels promotes atherogenesis, obesity-induced microvascular endothelial dysfunction impairs organ perfusion and thereby is causally related to the pathogenesis of ischemic heart disease, chronic kidney disease, intermittent claudication, exercise intolerance, and exacerbates cognitive decline in aging...
June 18, 2018: GeroScience
https://www.readbyqxmd.com/read/29968229/factors-that-positively-or-negatively-mediate-the-effects-of-age-on-working-memory-across-the-adult-life-span
#17
Selene Cansino, Frine Torres-Trejo, Cinthya Estrada-Manilla, Joyce Graciela Martínez-Galindo, Evelia Hernández-Ramos, Mariana Ayala-Hernández, Tania Gómez-Fernández, María Dolores Ramírez-González, Silvia Ruiz-Velasco
Working memory abilities significantly decrease with advancing age; hence, the search for factors that may increase or mitigate this decline is critical. Several factors have been identified that influence working memory; however, their effects have been mainly assessed separately and rarely together with other factors in the same sample. We examined 120 variables to search for factors that jointly act as mediators of working memory decay across the adult life span. A sample of 1652 healthy adults was assessed in spatial and verbal working memory domains...
June 2018: GeroScience
https://www.readbyqxmd.com/read/29961239/physiological-determinants-of-walking-effort-in-older-adults-should-they-be-targets-for-physical-activity-intervention
#18
Dain P LaRoche, Edward L Melanson, Morgan P Baumgartner, Breanna M Bozzuto, Victoria M Libby, Brittany N Marshall
Older adults do not get enough physical activity increasing risk for chronic disease and loss of physical function. The purpose of this study was to determine whether neuromuscular, metabolic, and cardiorespiratory indicators of walking effort explain daily activity in community-dwelling older adults. Sixteen women and fourteen men, 78 ± 8 years, performed a steady-state walk on a treadmill at 1.25 m s-1 while muscle activation, heart rate, lactate, respiratory exchange ratio, oxygen consumption (VO2 ), ventilation, and rating of perceived exertion (RPE) were recorded as markers of Walking Effort...
June 2018: GeroScience
https://www.readbyqxmd.com/read/29948868/the-potential-of-non-myeloablative-heterochronous-autologous-hematopoietic-stem-cell-transplantation-for-extending-a-healthy-life-span
#19
REVIEW
Primož Rožman
Aging is a complex multifactorial process, a prominent component being the senescence of the immune system. Consequently, immune-related diseases develop, including atherosclerosis, cancer, and life-threatening infections, which impact on health and longevity. Rejuvenating the aged immune system could mitigate these diseases, thereby contributing to longevity and health. Currently, an appealing option for rejuvenating the immune system is heterochronous autologous hematopoietic stem cell transplantation (haHSCT), where healthy autologous bone marrow/peripheral blood stem cells are collected during the youth of an individual, cryopreserved, and re-infused when he or she has reached an older age...
June 2018: GeroScience
https://www.readbyqxmd.com/read/29869736/composition-and-richness-of-the-serum-microbiome-differ-by-age-and-link-to-systemic-inflammation
#20
Thomas W Buford, Christy S Carter, William J VanDerPol, Dongquan Chen, Elliot J Lefkowitz, Peter Eipers, Casey D Morrow, Marcas M Bamman
Advanced age has been associated with alterations to the microbiome within the intestinal tract as well as intestinal permeability (i.e., "leaky gut"). Prior studies suggest that intestinal permeability may contribute to increases in systemic inflammation-an aging hallmark-possibly via microorganisms entering the circulation. Yet, no studies exist describing the state of the circulating microbiome among older persons. To compare microbiota profiles in serum between healthy young (20-35 years, n = 24) and older adults (60-75 years, n = 24) as well as associations between differential microbial populations and prominent indices of age-related inflammation...
June 2018: GeroScience
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