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Adam R Konopka, Benjamin F Miller
The anti-hyperglycemic medication metformin has potential to be the first drug tested to slow aging in humans. While the Targeting Aging with Metformin (TAME) proposal and other small-scale clinical trials have the potential to support aging as a treatment indication, we propose that the goals of the TAME trial might not be entirely consistent with the Geroscience goal of extending healthspan. There is expanding epidemiological support for the health benefits of metformin in individuals already diagnosed with overt chronic disease...
February 12, 2019: GeroScience
Bethany Grimmig, Charles Hudson, Lauren Moss, Melinda Peters, Meena Subbarayan, Edwin J Weeber, Paula C Bickford
The incidence of neurodegenerative disorders and cognitive impairment is increasing. Rising prevalence of age-related medical conditions is associated with a dramatic economic burden; therefore, developing strategies to manage these health concerns is of great public health interest. Nutritionally based interventions have shown promise in treatment of these age-associated conditions. Astaxanthin is a carotenoid with reputed neuroprotective properties in the context of disease and injury, while emerging evidence suggests that astaxanthin may also have additional biological activities relating to neurogenesis and synaptic plasticity...
February 9, 2019: GeroScience
Roee Holtzer, Rebecca Kraut, Meltem Izzetoglu, Kenny Ye
Neural inefficiency is inferred when higher brain activations are associated with similar or worse performance. Improved neural efficiency is achieved when task-related brain activations are reduced after practice. No information is available on the effect of fear-of-falling (FOF) on brain activation during walking. We hypothesized that the presence of FOF would be associated with neural inefficiency and with a delay in improving neural efficiency during dual-task walking. Task conditions included single-task walk (STW), Alpha (cognitive interference), and dual-task walk (DTW)...
February 9, 2019: GeroScience
Marissa J Schafer, Nathan K LeBrasseur
Growth differentiation factor 11 (GDF11) is a transforming growth factor β (TGFβ) protein that regulates aspects of central nervous system (CNS) formation and health throughout the lifespan. During development, GDF11 influences CNS patterning and the genesis, differentiation, maturation, and activity of new cells, which may be primarily dependent on local production and action. In the aged brain, exogenous, peripherally delivered GDF11 may enhance neurogenesis and angiogenesis, as well as improve neuropathological outcomes...
February 7, 2019: GeroScience
Yue Dong, Michelle A Digman, Gregory J Brewer
Nicotinamide adenine dinucleotide (reduced form: NADH) serves as a vital redox-energy currency for reduction-oxidation homeostasis and fulfilling energetic demands. While NADH exists as free and bound forms, only free NADH is utilized for complex I to power oxidative phosphorylation, especially important in neurons. Here, we studied how much free NADH remains available for energy production in mitochondria of old living neurons. We hypothesize that free NADH in neurons from old mice is lower than the levels in young mice and even lower in neurons from the 3xTg-AD Alzheimer's disease (AD) mouse model...
February 6, 2019: GeroScience
Angelia C Kirkpatrick, Julie A Stoner, Fabiola Donna-Ferreira, George C Malatinszky, Leslie D Guthery, James Scott, Calin I Prodan
As data on prevalence and etiology of dementia in American Indians are limited, we sought to determine rates and patterns of memory loss among American Indian veterans with vascular risk factors. Sixty consecutive outpatient American Indian veterans with a mean age of 64 years (range 50-86), without prior dementia or mild cognitive impairment (MCI), and with ≥ 2 vascular risk factors were enrolled. The Montreal Cognitive Assessment (MoCA) and the Beck Depression Inventory-II were used to screen for cognitive impairment and depression...
February 6, 2019: GeroScience
Lisa Liendl, Johannes Grillari, Markus Schosserer
Due to our aging population, understanding of the underlying molecular mechanisms constantly gains more and more importance. Senescent cells, defined by being irreversibly growth arrested and associated with a specific gene expression and secretory pattern, accumulate with age and thus contribute to several age-related diseases. However, their specific detection, especially in vivo, is still a major challenge. Raman microspectroscopy is able to record biochemical fingerprints of cells and tissues, allowing a distinction between different cellular states, or between healthy and cancer tissue...
February 4, 2019: GeroScience
Walter Arancio
Repetitive DNA sequences represent about half of the human genome. They have a central role in human biology, especially neurobiology, but are notoriously difficult to study. The purpose of this study was to quantify the transcription from repetitive sequences in a progerin-expressing cellular model of neuronal aging. Progerin is a nuclear protein causative of the Hutchinson-Gilford progeria syndrome that is also incrementally expressed during the normal aging process. A dedicated pipeline of analysis allowed to quantify transcripts containing repetitive sequences from RNAseq datasets oblivious of their genomic localization, tolerating a sufficient degree of mutational noise, all with low computational requirements...
January 8, 2019: GeroScience
Tracy L Habermehl, Kate C Parkinson, Gene B Hubbard, Yuji Ikeno, Jennifer I Engelmeyer, Björn Schumacher, Jeffrey B Mason
Cardiovascular disease, rare in premenopausal women, increases sharply at menopause and is typically accompanied by chronic inflammation. Previous work in our laboratory demonstrated that replacing senescent ovaries in post-reproductive mice with young, actively cycling ovaries restored many health benefits, including decreased cardiomyopathy and restoration of immune function. Our objective here was to determine if depletion of germ cells from young transplanted ovaries would alter the ovarian-dependent extension of life and health span...
December 13, 2018: GeroScience
Priya Balasubramanian, Delton Hall, Madhan Subramanian
Chronic sympathetic nervous system overactivity is a hallmark of aging and obesity and contributes to the development of cardiovascular diseases including hypertension and heart failure. The cause of this chronic sympathoexcitation in aging and obesity is multifactorial and centrally mediated. In this mini-review, we have provided an overview of the key and emerging central mechanisms contributing to the pathogenesis of sympathoexcitation in obesity and healthy aging, specifically focusing on hypertension. A clear understanding of these mechanisms will pave way for targeting the sympathetic nervous system for the treatment of cardiovascular diseases in obesity and aging...
December 5, 2018: GeroScience
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...
December 2018: GeroScience
Gabor A Fulop, Tamas Kiss, Stefano Tarantini, Priya Balasubramanian, Andriy Yabluchanskiy, Eszter Farkas, Ferenc Bari, Zoltan Ungvari, Anna Csiszar
Aging-induced pro-inflammatory phenotypic alterations of the cerebral vasculature critically contribute to the pathogenesis of vascular cognitive impairment. Cellular senescence is a fundamental aging process that promotes inflammation; however, its role in cerebrovascular aging remains unexplored. The present study was undertaken to test the hypothesis that advanced aging promotes cellular senescence in the cerebral vasculature. We found that in cerebral arteries of 24-month-old mice, expression of molecular markers of senescence (p16INK4a , p21) is upregulated as compared to that in young controls...
November 23, 2018: GeroScience
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
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
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
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
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
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
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No abstract text is available yet for this article.
August 2018: GeroScience
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
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