Aging, Lifespan & Longevity

Genome-Wide Screens Reveal that Resveratrol Induces Replicative Stress in Human Cells.

13 hours 58 minutes ago
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Genome-Wide Screens Reveal that Resveratrol Induces Replicative Stress in Human Cells.

Mol Cell. 2020 Jul 31;:

Authors: Benslimane Y, Bertomeu T, Coulombe-Huntington J, McQuaid M, Sánchez-Osuna M, Papadopoli D, Avizonis D, Russo MST, Huard C, Topisirovic I, Wurtele H, Tyers M, Harrington L

Abstract
Resveratrol is a natural product associated with wide-ranging effects in animal and cellular models, including lifespan extension. To identify the genetic target of resveratrol in human cells, we conducted genome-wide CRISPR-Cas9 screens to pinpoint genes that confer sensitivity or resistance to resveratrol. An extensive network of DNA damage response and replicative stress genes exhibited genetic interactions with resveratrol and its analog pterostilbene. These genetic profiles showed similarity to the response to hydroxyurea, an inhibitor of ribonucleotide reductase that causes replicative stress. Resveratrol, pterostilbene, and hydroxyurea caused similar depletion of nucleotide pools, inhibition of replication fork progression, and induction of replicative stress. The ability of resveratrol to inhibit cell proliferation and S phase transit was independent of the histone deacetylase sirtuin 1, which has been implicated in lifespan extension by resveratrol. These results establish that a primary impact of resveratrol on human cell proliferation is the induction of low-level replicative stress.

PMID: 32755594 [PubMed - as supplied by publisher]

Anabolic-androgenic steroids and brain injury: miRNA evaluation in users compared to cocaine abusers and elderly people.

13 hours 58 minutes ago
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Anabolic-androgenic steroids and brain injury: miRNA evaluation in users compared to cocaine abusers and elderly people.

Aging (Albany NY). 2020 Aug 03;12:

Authors: Sessa F, Salerno M, Cipolloni L, Bertozzi G, Messina G, Mizio GD, Asmundo A, Pomara C

Abstract
Anabolic-androgenic steroids (AASs) can be used to treat both hormonal diseases and other pathologies characterized by muscle loss (aging, cancer, and AIDS). Even if the adverse effects related to the misuse of AASs have been well studied in different systems and apparatuses, knowledge about brain damage is poor.In this scenario, this experimental study aimed to analyze the role of several microRNAs (miRNAs) in brain damage after AAS misuse, to better comprehend the underlying mechanisms. The research hypothesis at the base of this experimental study is that the chronic use of AASs may be associated to brain damage with a dysregulation of these miRNAs. Moreover, miRNA expression values were compared among three different groups, "AAS" group, "Cocaine" group and "Aging" group, in order to define if AAS brain damage can be compared with the brain impairment linked to aging and/or cocaine assumption.This experimental study revealed that the tested miRNAs (hsa-miR-21-5p, hsa-miR-34a-5p, hsa-miR-124-5p, hsa-miR-132-3p, and hsa-miR-144-3p) were overexpressed in all enrolled groups. In the light of the presented results, the identification of specific circulating and/or tissue biomarkers is challenging for the scientific community. Further studies with larger samples are needed to confirm these interesting findings.

PMID: 32756006 [PubMed - as supplied by publisher]

The whale shark genome reveals how genomic and physiological properties scale with body size.

1 day 14 hours ago
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The whale shark genome reveals how genomic and physiological properties scale with body size.

Proc Natl Acad Sci U S A. 2020 Aug 04;:

Authors: Weber JA, Park SG, Luria V, Jeon S, Kim HM, Jeon Y, Bhak Y, Jun JH, Kim SW, Hong WH, Lee S, Cho YS, Karger A, Cain JW, Manica A, Kim S, Kim JH, Edwards JS, Bhak J, Church GM

Abstract
The endangered whale shark (Rhincodon typus) is the largest fish on Earth and a long-lived member of the ancient Elasmobranchii clade. To characterize the relationship between genome features and biological traits, we sequenced and assembled the genome of the whale shark and compared its genomic and physiological features to those of 83 animals and yeast. We examined the scaling relationships between body size, temperature, metabolic rates, and genomic features and found both general correlations across the animal kingdom and features specific to the whale shark genome. Among animals, increased lifespan is positively correlated to body size and metabolic rate. Several genomic traits also significantly correlated with body size, including intron and gene length. Our large-scale comparative genomic analysis uncovered general features of metazoan genome architecture: Guanine and cytosine (GC) content and codon adaptation index are negatively correlated, and neural connectivity genes are longer than average genes in most genomes. Focusing on the whale shark genome, we identified multiple features that significantly correlate with lifespan. Among these were very long gene length, due to introns being highly enriched in repetitive elements such as CR1-like long interspersed nuclear elements, and considerably longer neural genes of several types, including connectivity, activity, and neurodegeneration genes. The whale shark genome also has the second slowest evolutionary rate observed in vertebrates to date. Our comparative genomics approach uncovered multiple genetic features associated with body size, metabolic rate, and lifespan and showed that the whale shark is a promising model for studies of neural architecture and lifespan.

PMID: 32753383 [PubMed - as supplied by publisher]

Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice.

1 day 14 hours ago
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Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice.

Aging Cell. 2020 Aug 04;:e13208

Authors: Florian MC, Leins H, Gobs M, Han Y, Marka G, Soller K, Vollmer A, Sakk V, Nattamai KJ, Rayes A, Zhao X, Setchell K, Mulaw M, Wagner W, Zheng Y, Geiger H

Abstract
Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain-of-activity mouse model presents with a premature aging-like phenotype and with decreased lifespan. These data suggest a causal connection between elevated activity of Cdc42, aging, and reduced lifespan. Here, we demonstrate that systemic treatment of aged (75-week-old) female C57BL/6 mice with a Cdc42 activity-specific inhibitor (CASIN) for 4 consecutive days significantly extends average and maximum lifespan. Moreover, aged CASIN-treated animals displayed a youthful level of the aging-associated cytokines IL-1β, IL-1α, and INFγ in serum and a significantly younger epigenetic clock as based on DNA methylation levels in blood cells. Overall, our data show that systemic administration of CASIN to reduce Cdc42 activity in aged mice extends murine lifespan.

PMID: 32755011 [PubMed - as supplied by publisher]

Accelerated epigenetic aging as a risk factor for chronic obstructive pulmonary disease and decreased lung function in two prospective cohort studies.

2 days 15 hours ago
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Accelerated epigenetic aging as a risk factor for chronic obstructive pulmonary disease and decreased lung function in two prospective cohort studies.

Aging (Albany NY). 2020 Aug 03;12:

Authors: Breen M, Nwanaji-Enwerem JC, Karrasch S, Flexeder C, Schulz H, Waldenberger M, Kunze S, Ollert M, Weidinger S, Colicino E, Gao X, Wang C, Shen J, Just AC, Vokonas P, Sparrow D, Hou L, Schwartz JD, Baccarelli AA, Peters A, Ward-Caviness CK

Abstract
Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

PMID: 32747609 [PubMed - as supplied by publisher]

Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration.

2 days 15 hours ago
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Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration.

Aging Cell. 2020 Aug 04;:e13210

Authors: Sun L, Zhang J, Chen W, Chen Y, Zhang X, Yang M, Xiao M, Ma F, Yao Y, Ye M, Zhang Z, Chen K, Chen F, Ren Y, Ni S, Zhang X, Yan Z, Sun ZR, Zhou HM, Yang H, Xie S, Haque ME, Huang K, Yang Y

Abstract
How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co-expression analysis on human patient substantia nigra-specific microarray datasets to identify potential novel disease-related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin-remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent aging-dependent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Furthermore, down-regulation of SMARCA4 specifically in the dopaminergic neurons prevented shortening of life span caused by α-synuclein and LRRK2. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK-ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down-regulation of SMARCA4 or drug inhibition of MEK/ERK also mitigated mitochondrial defects in PINK1 (a PD-associated gene)-deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age-related disorders including PD.

PMID: 32749068 [PubMed - as supplied by publisher]

Ubiquinol supplementation in elderly patients undergoing aortic valve replacement: biochemical and clinical aspects.

3 days 16 hours ago
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Ubiquinol supplementation in elderly patients undergoing aortic valve replacement: biochemical and clinical aspects.

Aging (Albany NY). 2020 Jul 31;12:

Authors: Orlando P, Sabbatinelli J, Silvestri S, Marcheggiani F, Cirilli I, Dludla PV, Molardi A, Nicolini F, Tiano L

Abstract
Epidemiological data show a rise in the mean age of patients affected by heart disease undergoing cardiac surgery. Senescent myocardium reduces the tolerance to ischemic stress and there are indications about age-associated deficit in post-operative cardiac performance. Coenzyme Q10 (CoQ10), and more specifically its reduced form ubiquinol (QH), improve several conditions related to bioenergetic deficit or increased exposure to oxidative stress. This trial (Eudra-CT 2009-015826-13) evaluated the clinical and biochemical effects of ubiquinol in 50 elderly patients affected by severe aortic stenosis undergoing aortic valve replacement and randomized to either placebo or 400 mg/day ubiquinol from 7 days before to 5 days after surgery. Plasma and cardiac tissue CoQ10 levels and oxidative status, circulating troponin I, CK-MB (primary endpoints), IL-6 and S100B were assessed. Moreover, main cardiac adverse effects, NYHA class, contractility and myocardial hypertrophy (secondary endpoints) were evaluated during a 6-month follow-up visit. Ubiquinol treatment counteracted the post-operative plasma CoQ10 decline (p<0.0001) and oxidation (p=0.038) and curbed the post-operative increase in troponin I (QH, 1.90 [1.47-2.48] ng/dL; placebo, 4.03 [2.45-6.63] ng/dL; p=0.007) related to cardiac surgery. Moreover, ubiquinol prevented the adverse outcomes that might have been associated with defective left ventricular ejection fraction recovery in elderly patients.

PMID: 32741773 [PubMed - as supplied by publisher]

Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD+ redox.

3 days 16 hours ago
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Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD+ redox.

Aging Cell. 2020 Aug 03;:e13206

Authors: Yang L, Lin X, Tang H, Fan Y, Zeng S, Jia L, Li Y, Shi Y, He S, Wang H, Hu Z, Gong X, Liang X, Yang Y, Liu X

Abstract
Mammals' aging is correlated with the accumulation of somatic heteroplasmic mitochondrial DNA (mtDNA) mutations. Whether and how aging accumulated mtDNA mutations modulate fertility remains unknown. Here, we analyzed oocyte quality of young (≤30 years old) and elder (≥38 years old) female patients and show the elder group had lower blastocyst formation rate and more mtDNA point mutations in oocytes. To test the causal role of mtDNA point mutations on infertility, we used polymerase gamma (POLG) mutator mice. We show that mtDNA mutation levels inversely correlate with fertility, interestingly mainly affecting not male but female fertility. mtDNA mutations decrease female mice's fertility by reducing ovarian primordial and mature follicles. Mechanistically, accumulation of mtDNA mutations decreases fertility by impairing oocyte's NADH/NAD+ redox state, which could be rescued by nicotinamide mononucleotide treatment. For the first time, we answer the fundamental question of the causal effect of age-accumulated mtDNA mutations on fertility and its sex dependence, and show its distinct metabolic controlling mechanism.

PMID: 32744417 [PubMed - as supplied by publisher]

Single molecule poly(A) tail-seq shows LARP4 opposes deadenylation through mRNA lifespan with most impact on short tails.

3 days 16 hours ago
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Single molecule poly(A) tail-seq shows LARP4 opposes deadenylation through mRNA lifespan with most impact on short tails.

Elife. 2020 Aug 03;9:

Authors: Mattijssen S, Iben JR, Li T, Coon SL, Maraia RJ

Abstract
La-related protein 4 (LARP4) directly binds both poly(A) and poly(A)-binding protein (PABP). LARP4 was shown to promote poly(A) tail (PAT) lengthening and stabilization of individual mRNAs presumably by protection from deadenylation (Mattijssen et al., 2017). We developed a nucleotide resolution transcriptome-wide, single molecule SM-PAT-seq method. This revealed LARP4 effects on a wide range of PAT lengths for human mRNAs and mouse mRNAs from LARP4 knockout (KO) and control cells. LARP4 effects are clear on long PAT mRNAs but become more prominent at 30-75 nucleotides. We also analyzed time courses of PAT decay transcriptome-wide and for ~200 immune response mRNAs. This demonstrated accelerated deadenylation in KO cells on PATs <75 nucleotides and phasing features consistent with greater PABP dissociation in the absence of LARP4. Thus, LARP4 shapes PAT profiles throughout mRNA lifespan and with impact on mRNA decay at short lengths known to sensitize PABP dissociation in response to deadenylation machinery.

PMID: 32744499 [PubMed - as supplied by publisher]

Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis.

3 days 16 hours ago

Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis.

Aging (Albany NY). 2020 Aug 03;12:

Authors: Varela-Eirín M, Carpintero-Fernández P, Sánchez-Temprano A, Varela-Vázquez A, Paíno CL, Casado-Díaz A, Continente AC, Mato V, Fonseca E, Kandouz M, Blanco A, Caeiro JR, Mayán MD

Abstract
Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our in vitro results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease.

PMID: 32745074 [PubMed - as supplied by publisher]

A HIERARCHICAL MODEL FOR THE CONTROL OF EPIGENETIC AGING IN MAMMALS.

4 days 17 hours ago

A HIERARCHICAL MODEL FOR THE CONTROL OF EPIGENETIC AGING IN MAMMALS.

Ageing Res Rev. 2020 Jul 30;:101134

Authors: Lehmann M, Canatelli-Mallat M, Chiavellini P, Goya RG

Abstract
Regulatory mechanisms range from a single level of control in simple metazoans to multi-level hierarchical control networks in higher animals. Organismal regulation encompasses homeostatic and circadian networks that are interconnected, with no documented exceptions. The epigenetic clock is a highly accurate biomarker of age in humans, defined by a mathematical algorithm based on the methylation of a subset of age-related CpG sites on DNA. Experimental evidence suggests the existence of an underlying regulatory mechanism. By analogy with other integrative systems as the neuroendocrine-immune network and the circadian clocks, a hierarchical organization in the control of the ticking rate of the epigenetic clock is hypothesized here. The hierarchical organization of the neuroendocrine, immune and circadian systems is briefly reviewed. This is followed by a brief review of the epigenetic clock at cell level. Finally, different lines of indirect evidence, consistent with the existence of a central pacemaker controlling the ticking rate of the epigenetic clock at organismal level are discussed. The concluding remarks put the hierarchical model proposed for the control of the clock into an evolutionary perspective. Within this perspective, the present hypothesis is intended as a conceptual outline based on designs consistently favored by evolution in higher animals.

PMID: 32739456 [PubMed - as supplied by publisher]

Rapid senescence-like response after acute injury.

4 days 17 hours ago

Rapid senescence-like response after acute injury.

Aging Cell. 2020 Aug 02;:e13201

Authors: Chu X, Wen J, Raju RP

Abstract
Cellular senescence is a state of irreversible growth arrest. Short-term programmed senescence such as in embryonic development and slowly progressing senescence as in aging are both well described. However, acute senescence in living organisms is not well understood. We hypothesized that hemorrhagic shock injury (HI) caused by whole body hypoxia and nutrient deprivation, resulting in organ dysfunction due to severe blood loss, could lead to acute senescence in vivo. Our experiments, for the first time, demonstrate a rapidly emerged, senolytics-responsive, senescence-like response in the rat liver in less than five hr following hemorrhagic shock. We conclude that the senescence, or pseudosenescence, observed is necessary to maintain tissue homeostasis following the injury.

PMID: 32741083 [PubMed - as supplied by publisher]

CD8+ T cells are increased in the subventricular zone with physiological and pathological aging.

4 days 17 hours ago

CD8+ T cells are increased in the subventricular zone with physiological and pathological aging.

Aging Cell. 2020 Aug 01;:e13198

Authors: Moreno-Valladares M, Moreno-Cugnon L, Silva TM, Garcés JP, Saenz-Antoñanzas A, Álvarez-Satta M, Matheu A

Abstract
Age-related cognitive decline and neurodegenerative diseases are associated with less functional neurogenic niches. It has been recently shown that aged subventricular zone (SVZ) suffers an infiltration of T cells, which affects neural stem cell activity in mice. Whether this occurs in human neurogenic niches or to which extent T-cell infiltration is also taking place in neurodegenerative diseases remains unknown. In this work, we studied the presence of T cells in both human neurogenic niches in young and old individuals. There was a significant increase in the number of CD3+ and CD8+ T cells in the SVZ of elderly individuals, which was not detected in the dentate gyrus. Moreover, we also found CD3+ and CD8+ T cells in the SVZ of individuals with neurodegenerative diseases. However, T-cell count was similar when compared non-neuropathological elderly with disease diagnosed patients. Our study reveals the infiltration of T cells in old human brains, particularly in the SVZ under non-pathological conditions and also in neurodegenerative contexts.

PMID: 32741087 [PubMed - as supplied by publisher]

Wild chimpanzees exhibit humanlike aging of glucocorticoid regulation.

6 days 20 hours ago
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Wild chimpanzees exhibit humanlike aging of glucocorticoid regulation.

Proc Natl Acad Sci U S A. 2020 04 14;117(15):8424-8430

Authors: Emery Thompson M, Fox SA, Berghänel A, Sabbi KH, Phillips-Garcia S, Enigk DK, Otali E, Machanda ZP, Wrangham RW, Muller MN

Abstract
Cortisol, a key product of the stress response, has critical influences on degenerative aging in humans. In turn, cortisol production is affected by senescence of the hypothalamic-pituitary-adrenal (HPA) axis, leading to progressive dysregulation and increased cortisol exposure. These processes have been studied extensively in industrialized settings, but few comparative data are available from humans and closely related species living in natural environments, where stressors are very different. Here, we examine age-related changes in urinary cortisol in a 20-y longitudinal study of wild chimpanzees (n = 59 adults) in the Kanyawara community of Kibale National Park, Uganda. We tested for three key features of HPA aging identified in many human studies: increased average levels, a blunted diurnal rhythm, and enhanced response to stressors. Using linear mixed models, we found that aging was associated with a blunting of the diurnal rhythm and a significant linear increase in cortisol, even after controlling for changes in dominance rank. These effects did not differ by sex. Aging did not increase sensitivity to energetic stress or social status. Female chimpanzees experienced their highest levels of cortisol during cycling (versus lactation), and this effect increased with age. Male chimpanzees experienced their highest levels when exposed to sexually attractive females, but this effect was diminished by age. Our results indicate that chimpanzees share some key features of HPA aging with humans. These findings suggest that impairments of HPA regulation are intrinsic to the aging process in hominids and are side effects neither of extended human life span nor of atypical environments.

PMID: 32229565 [PubMed - indexed for MEDLINE]

Paraventricular hypothalamus mediates diurnal rhythm of metabolism.

6 days 20 hours ago
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Paraventricular hypothalamus mediates diurnal rhythm of metabolism.

Nat Commun. 2020 Jul 30;11(1):3794

Authors: Kim ER, Xu Y, Cassidy RM, Lu Y, Yang Y, Tian J, Li DP, Van Drunen R, Ribas-Latre A, Cai ZL, Xue M, Arenkiel BR, Eckel-Mahan K, Xu Y, Tong Q

Abstract
Defective rhythmic metabolism is associated with high-fat high-caloric diet (HFD) feeding, ageing and obesity; however, the neural basis underlying HFD effects on diurnal metabolism remains elusive. Here we show that deletion of BMAL1, a core clock gene, in paraventricular hypothalamic (PVH) neurons reduces diurnal rhythmicity in metabolism, causes obesity and diminishes PVH neuron activation in response to fast-refeeding. Animal models mimicking deficiency in PVH neuron responsiveness, achieved through clamping PVH neuron activity at high or low levels, both show obesity and reduced diurnal rhythmicity in metabolism. Interestingly, the PVH exhibits BMAL1-controlled rhythmic expression of GABA-A receptor γ2 subunit, and dampening rhythmicity of GABAergic input to the PVH reduces diurnal rhythmicity in metabolism and causes obesity. Finally, BMAL1 deletion blunts PVH neuron responses to external stressors, an effect mimicked by HFD feeding. Thus, BMAL1-driven PVH neuron responsiveness in dynamic activity changes involving rhythmic GABAergic neurotransmission mediates diurnal rhythmicity in metabolism and is implicated in diet-induced obesity.

PMID: 32732906 [PubMed - in process]

Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages.

6 days 20 hours ago
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Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages.

Nat Commun. 2020 Jul 30;11(1):3820

Authors: Hirata T, Arai Y, Yuasa S, Abe Y, Takayama M, Sasaki T, Kunitomi A, Inagaki H, Endo M, Morinaga J, Yoshimura K, Adachi T, Oike Y, Takebayashi T, Okano H, Hirose N

Abstract
Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105-109 years), 288 centenarians (100-104 years), and 531 very old people (85-99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity.

PMID: 32732919 [PubMed - in process]

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Aging, Lifespan & Longevity
NCBI: db=pubmed; Term=(Rejuvenation[Title/Abstract] OR Rejuvenate[Title/Abstract] OR Senescent[Title/Abstract] OR Senescence[Title/Abstract] OR Aging[Title/Abstract] OR Ageing[Title/Abstract] OR Lifespan[Title/Abstract] OR Longevity[Title/Abstract] OR Alzheimer[Title/Abstract]) AND ("Nature"[Journal] OR "Science (New York, N.Y.)"[Journal] OR "Cell"[Journal] OR "The New England Journal Of Medicine"[Journal] OR "Lancet"[Journal] OR "Nature Reviews Molecular Cell Biology"[Journal] OR "Nature Medicine"[Journal] OR "Nature Communications"[Journal] OR "Cell Stem Cell"[Journal] OR "Cell Metabolism"[Journal] OR "Nature Neuroscience"[Journal] OR "Nature Cell Biology"[Journal] OR "Molecular Cell"[Journal] OR "Nature Chemical Biology"[Journal] OR "Genome Biology"[Journal] OR "Plos Medicine"[Journal] OR "Nucleic Acids Research"[Journal] OR "Autophagy"[Journal] OR "Embo J."[Journal] OR "Genome Research"[Journal] OR "Developmental Cell"[Journal] OR "Genes & Development"[Journal] OR "Proceedings Of The National Academy Of Sciences Of The United States Of America"[Journal] OR "Plos Biology"[Journal] OR "Ageing Research Reviews"[Journal] OR "The Journal Of Cell Biology"[Journal] OR "Molecular and cellular biology"[Journal] OR "Aging Cell"[Journal] OR "Elife"[Journal] OR "Aging"[Journal]) AND ("2020/01/01"[Date - Publication] : "3000"[Date - Publication])
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