bims-longev 2023-02-19 papers

bims-longev

Biomed News

on Longevity

Issue of 2023‒02‒19
thirteen papers selected by
Andreea Nitescu

Mitophagy: A promising therapeutic target for neuroprotection during aging and age-related diseases.
Circular RNA Involvement in Aging and Longevity.
Reverse electron transfer is activated during aging and contributes to aging and age-related disease.
Effects of β-blockers on all-cause mortality in patients with diabetes and coronary heart disease: A systematic review and meta-analysis.
A Year at the Forefront of Proteostasis and Aging.
Ageotypes revisited: The brain and central nervous system dysfunction as a major nutritional and lifestyle target for healthy aging.
Contribution of Biological Age-Predictive Biomarkers to Nutrition Research: A Systematic Review of the Current Evidence and Implications for Future Research and Clinical Practice.
Transposable elements and their role in aging.
Young Exosome Bio-nanoparticles Restore Aging-Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity.
Mitochondrial miRNA as epigenomic signatures: Visualizing aging-associated heart diseases through a new lens.
Targeting IGF1R signaling for brain aging and Alzheimer's disease.
Are serum uric acid levels predictors of cardiovascular risk? An update.
Plasticity After Hearing Rehabilitation in the Aging Brain.

Br J Pharmacol. 2023 Feb 15.

Mitophagy: A promising therapeutic target for neuroprotection during aging and age-related diseases.

Ela Mishra, Mahendra Kumar Thakur.

  Mitochondria and mitochondria-mediated signaling pathways are known to control synaptic signaling as well as long-lasting changes in neuronal structure and function. Mitochondrial impairment is linked to synaptic dysfunction in normal aging and age-associated neurodegenerative ailments including Parkinson's disease (PD) and Alzheimer's disease (AD). Both proteolysis and mitophagy perform a major role in neuroprotection by maintaining a healthy mitochondrial population during aging. Mitophagy, a highly evolutionarily conserved cellular process, helps in the clearance of damaged mitochondria and thereby maintains the mitochondrial and metabolic balance, energy supply, neuronal survival, and neuronal health. Besides the maintenance of brain homeostasis, hippocampal mitophagy also helps in synapse formation, axonal development, dopamine release, and long-term depression. In contrast, defective mitophagy contributes to aging and age-related neurodegeneration by promoting the accumulation of damaged mitochondria leading to cellular dysfunction. Exercise, stress management, maintaining healthy mitochondrial dynamics, and administering natural or synthetic pharmacological compounds are some of the strategies used for neuroprotection during aging and age-related neurological diseases. The current review discusses the impact of defective mitophagy in aging and age-associated neurodegenerative conditions, the underlying molecular pathways, and potential therapies based on recently elucidated mitophagy-inducing strategies.

Keywords:  Aging; Mitochondrial dysfunction; Mitophagy; Neurodegeneration; Pharmacological compounds; Therapeutic interventions

DOI:  https://doi.org/10.1111/bph.16062
Curr Genomics. 2022 Nov 18. 23(5): 318-325

Circular RNA Involvement in Aging and Longevity.

Ruize Niu, Jia Liu.

  Background: Circular RNAs (circRNAs) are transcribed by RNA polymerase II and are mostly generated by the back-splicing of exons in the protein-coding gene. Massive circRNAs are reported to be differentially expressed in different species, implicating their prospects as aging biomarkers or regulators in the aging progression.Methods: The possible role of circRNAs in aging and longevity was reviewed by the query of circRNAs from literature reports related to tissue, organ or cellular senescence, and individual longevity.
Results: A number of circRNAs have been found to positively and negatively modulate aging and longevity through canonical aging pathways in the invertebrates Caenorhabditis elegans and Drosophila. Recent studies have also shown that circRNAs regulate age-related processes and pathologies such various mammalian tissues, as the brain, serum, heart, and muscle. Besides, three identified representative circRNAs (circSfl, circGRIA1, and circNF1-419) were elucidated to correlate with aging and longevity.
Conclusion: This review outlined the current studies of circRNAs in aging and longevity, highlighting the role of circRNAs as a biomarker of aging and as a regulator of longevity.

Keywords:  Aging; age-related diseases; biomarkers; circular RNA; longevity; microRNAs

DOI:  https://doi.org/10.2174/1389202923666220927110258
EMBO Rep. 2023 Feb 16. e55548

Reverse electron transfer is activated during aging and contributes to aging and age-related disease.

Suman Rimal, Ishaq Tantray, Yu Li, Tejinder Pal Khaket, Yanping Li, Sunil Bhurtel, Wen Li, Cici Zeng, Bingwei Lu.

  Mechanisms underlying the depletion of NAD+ and accumulation of reactive oxygen species (ROS) in aging and age-related disorders remain poorly defined. We show that reverse electron transfer (RET) at mitochondrial complex I, which causes increased ROS production and NAD+ to NADH conversion and thus lowered NAD+ /NADH ratio, is active during aging. Genetic or pharmacological inhibition of RET decreases ROS production and increases NAD+ /NADH ratio, extending the lifespan of normal flies. The lifespan-extending effect of RET inhibition is dependent on NAD+ -dependent Sirtuin, highlighting the importance of NAD+ /NADH rebalance, and on longevity-associated Foxo and autophagy pathways. RET and RET-induced ROS and NAD+ /NADH ratio changes are prominent in human induced pluripotent stem cell (iPSC) model and fly models of Alzheimer's disease (AD). Genetic or pharmacological inhibition of RET prevents the accumulation of faulty translation products resulting from inadequate ribosome-mediated quality control, rescues relevant disease phenotypes, and extends the lifespan of Drosophila and mouse AD models. Deregulated RET is therefore a conserved feature of aging, and inhibition of RET may open new therapeutic opportunities in the context of aging and age-related diseases including AD.

Keywords:  Alzheimer's disease; NAD+/NADH ratio; lifespan; mitochondrial complex I; reverse electron transport

DOI:  https://doi.org/10.15252/embr.202255548
Front Cell Dev Biol. 2023 ;11 1076107

Effects of β-blockers on all-cause mortality in patients with diabetes and coronary heart disease: A systematic review and meta-analysis.

Shiqi Chen, Panhui Tian, Dannya Estau, Zijian Li.

  Beta-blockers have been considered as an effective treatment in secondary prevention of coronary heart disease (CHD). However, there is still disputed whether β-blockers can increase all-cause mortality in patients with coronary heart disease and diabetes mellitus (DM). Here, our systematic review and meta-analysis is aiming to assess the effects of β-blockers on all-cause mortality in patients with coronary heart disease and diabetes mellitus. Four databases (PubMed, Embase, Cochrane Library and Web of Science) and other sources were searched to collect randomized controlled trials (RCTs) and cohort studies related to the treatment of β-blockers for coronary heart disease and diabetes mellitus patients. We further evaluated quality of evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Finally, a total of 16,188 records were identified, and four randomized controlled trials and six cohort studies (206,490 patients) were included. Random effects analysis revealed that β-blockers combined with routine treatment (RT) significantly decreased all-cause mortality in patients with coronary heart disease and diabetes mellitus compared with RT in control group (RR 0.59, 95% CI 0.47 to 0.75; p < 0.000 01; I2 = 72%). Subgroup analysis of all-cause mortality by the subtype of diabetes mellitus and definite MI patients (RR 0.54, 95% CI 0.45 to 0.65, p < 0.000 01, I2 = 29%) and the subtype of randomized controlled trials (RR 0.49, 95% CI 0.32 to 0.76, p = 0.001, I2 = 0%) indicated a relatively small heterogeneity and stable results. β-blockers application significantly reduced cardiovascular death as well (RR 0.56, 95% CI 0.42 to 0.74; p < 0.000 1; I2 = 0%). Our meta-analysis provided critical evidence of β-blockers treatment for patients with coronary heart disease (especially MI type) and diabetes mellitus, and discussed the advantages and potential metabolic risks for the clinical use of β-blockers. This study suggested that β-blockers application may improve all-cause mortality and cardiovascular death in coronary heart disease (especially MI type) and diabetes mellitus patients. However, given a small number of included studies, the aforementioned conclusion should be confirmed in a multi-center, large-scale, and strictly designed trial.

Keywords:  all-cause mortality; beta-blockers; coronary heart disease; diabetes mellitus; systematic review

DOI:  https://doi.org/10.3389/fcell.2023.1076107
Biol Open. 2023 Feb 15. pii: bio059750. [Epub ahead of print]12(2):

A Year at the Forefront of Proteostasis and Aging.

Maximilian A Thompson, Evandro A De-Souza.

  During aging, animals experience a decline in proteostasis activity, including loss of stress-response activation, culminating in the accumulation of misfolded proteins and toxic aggregates, which are causal in the onset of some chronic diseases. Finding genetic and pharmaceutical treatments that can increase organismal proteostasis and lengthen life is an ongoing goal of current research. The regulation of stress responses by cell non-autonomous mechanisms appears to be a potent way to impact organismal healthspan. In this Review, we cover recent findings in the intersection of proteostasis and aging, with a special focus on articles and preprints published between November 2021 and October 2022. A significant number of papers published during this time increased our understanding of how cells communicate with each other during proteotoxic stress. Finally, we also draw attention to emerging datasets that can be explored to generate new hypotheses that explain age-related proteostasis collapse.

Keywords:  Cell non-autonomous response; Heat shock response; Longevity; Protein homeostasis; UPR

DOI:  https://doi.org/10.1242/bio.059750
Maturitas. 2023 Feb 06. pii: S0378-5122(23)00022-1. [Epub ahead of print]170 51-57

Ageotypes revisited: The brain and central nervous system dysfunction as a major nutritional and lifestyle target for healthy aging.

Maria G Grammatikopoulou, Efstathios Skoufas, Spyridon Kanellakis, Despina Sanoudou, Georgios A Pavlopoulos, Aristides G Eliopoulos, Kalliopi K Gkouskou.

  Undeniably, biological age can significantly differ between individuals of similar chronological age. Longitudinal, deep multi-omic profiling has recently enabled the identification of individuals with distinct aging phenotypes, termed 'ageotypes'. This effort has provided a plethora of data and new insights into the diverse molecular mechanisms presumed to drive aging. Translational opportunities stemming from this knowledge continue to evolve, providing an opportunity for the provision of nutritional interventions aiming to decelerate the aging process. In this framework, the contemporary ageotypes classification was revisited via in silico analyses, with the brain and nervous system being identified as the primary targets of age-related biomolecules, acting through inflammatory and metabolic pathways. Nutritional and lifestyle factors affecting these pathways in the brain and central nervous system that could help guide personalized recommendations for the attainment of healthy aging are discussed.

Keywords:  Bioinformatics; Brain; CNS; Genetics; Inflammaging; Nutriomics; Nutrition; Omics; ageotype; in silico

DOI:  https://doi.org/10.1016/j.maturitas.2023.01.013
Adv Nutr. 2022 Sep;pii: S2161-8313(23)00049-2. [Epub ahead of print]13(5): 1930-1946

Contribution of Biological Age-Predictive Biomarkers to Nutrition Research: A Systematic Review of the Current Evidence and Implications for Future Research and Clinical Practice.

George Siopis, Judi Porter.

  The global population is living longer; however, not everyone ages at the same rate with regard to their physical and cognitive abilities and their vulnerability to certain diseases and death. This review aimed to synthesize the contribution of biological age-predictive biomarkers to nutrition research and highlight the implications for future research and clinical practice. MEDLINE, CINAHL, and Cochrane CENTRAL were systematically searched on 30 September 2021 for randomized controlled trials and cross-sectional studies examining the association between nutrition and biological age in older adults reporting on genetic, clinical, or molecular biomarkers of biological aging. Cochrane's ROB 2 and ROBINS-I were used to assess the quality of included studies. Synthesis was undertaken narratively. Of 1245 records identified from the search, 13 studies from 8 countries and territories, involving 5043 participants, were included. Seven studies assessed associations between nutrient food intake and telomere attrition, reporting protective effects for branched-chain amino acids, calcium and vitamin D, and a diet of a lower inflammatory index; whereas they found shorter telomeres in people consuming more processed foods and arachidonic acid and other proinflammatory compounds. Five studies examined the associations between plasma nutrition biomarkers and cognitive function, and found a protective effect for HDL cholesterol, lycopene, carotenoids, ω-3 and ω-6 fatty acids, and vitamins B, C, D, and E; whereas trans fatty acids and fibrinogen correlated with a decline in cognitive function. One study used Horvath's clock and reported the epigenetic rejuvenation effect of a Mediterranean diet. In conclusion, biological aging was negatively associated with an anti-inflammatory diet. However, a few studies did not control for the confounding effect of other lifestyle factors. Future research should address this and also assess the synergistic effect of different nutrients, their combinations, and evaluate their dose-response relations. Nutrition practice can incorporate updated screening procedures for older people that include relevant biological aging nutrition markers, leading to anti-aging precision nutrition therapy. The methodology of this systematic review was registered in PROSPERO (CRD42021288122).

Keywords:  aging; cognitive function; diet; dietetics; epigenetics; geriatrics; gerontology; nutritional epidemiology; telomere length

DOI:  https://doi.org/10.1093/advances/nmac060
Ageing Res Rev. 2023 Feb 10. pii: S1568-1637(23)00040-5. [Epub ahead of print]86 101881

Transposable elements and their role in aging.

Elena Yushkova, Alexey Moskalev.

  Transposable elements (TEs) are an important part of eukaryotic genomes. The role of somatic transposition in aging, carcinogenesis, and other age-related diseases has been determined. This review discusses the fundamental properties of TEs and their complex interactions with cellular processes, which are crucial for understanding the diverse effects of their activity on the genetics and epigenetics of the organism. The interactions of TEs with recombination, replication, repair, and chromosomal regulation; the ability of TEs to maintain a balance between their own activity and repression, the involvement of TEs in the creation of new or alternative genes, the expression of coding/non-coding RNA, and the role in DNA damage and modification of regulatory networks are reviewed. The contribution of the derepressed TEs to age-dependent effects in individual cells/tissues in different organisms was assessed. Conflicting information about TE activity under stress as well as theories of aging mechanisms related to TEs is discussed. On the one hand, transposition activity in response to stressors can lead to organisms acquiring adaptive innovations of great importance for evolution at the population level. On the other hand, the TE expression can cause decreased longevity and stress tolerance at the individual level. The specific features of TE effects on aging processes in germline and soma and the ways of their regulation in cells are highlighted. Recent results considering somatic mutations in normal human and animal tissues are indicated, with the emphasis on their possible functional consequences. In the context of aging, the correlation between somatic TE activation and age-related changes in the number of proteins required for heterochromatin maintenance and longevity regulation was analyzed. One of the original features of this review is a discussion of not only effects based on the TEs insertions and the associated consequences for the germline cell dynamics and somatic genome, but also the differences between transposon- and retrotransposon-mediated structural genome changes and possible phenotypic characteristics associated with aging and various age-related pathologies. Based on the analysis of published data, a hypothesis about the influence of the species-specific features of number, composition, and distribution of TEs on aging dynamics of different animal genomes was formulated.

Keywords:  Age-related pathologies; Aging; Derepression; Germline cells; Somatic genome; Transposable elements; Transpositions

DOI:  https://doi.org/10.1016/j.arr.2023.101881
Adv Mater. 2023 Feb 13. e2211602

Young Exosome Bio-nanoparticles Restore Aging-Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity.

Shanshan Jin, Yu Wang, Xiaolan Wu, Zixin Li, Lisha Zhu, Yuting Niu, Yongsheng Zhou, Yan Liu.

  Aging impairs tendon stem cell function and homeostasis, however, effective treatments for aging-induced tendon diseases are lacking. Exosomes are naturally derived nanoparticles that contain bioactive molecules, and therefore, have attracted great interests in tissue engineering and regenerative medicine. In this study, we show that young exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED-Exos) possess abundant anti-aging signals. These young bio-nanoparticles can alleviate the aging phenotypes of aged tendon stem/progenitor cells (AT-SCs) and maintain their tenogenic capacity. Mechanistically, SHED-Exos modulate histone methylation and inhibit nuclear factor-κB to reverse AT-SC aging. In a naturally aging mouse model, systemic administration of SHED-Exo bio-nanoparticles retards tendon degeneration. Interestingly, local delivery of SHED-Exos-loaded microspheres confers anti-aging phenotypes, including reduced senescent cells and decreased ectopic bone formation, and thereby functionally and structurally rescuing endogenous tendon regeneration and repair capacity in aged rats. Overall, SHED-Exos, as natural bioactive nanoparticles, have promising translational and therapeutic potential for aging-related diseases. This article is protected by copyright. All rights reserved.

Keywords:  Exosome nanoparticles; hydrogel microspheres; senescence; tendon regeneration; tendon stem/progenitor cell

DOI:  https://doi.org/10.1002/adma.202211602
Ageing Res Rev. 2023 Feb 11. pii: S1568-1637(23)00041-7. [Epub ahead of print]86 101882

Mitochondrial miRNA as epigenomic signatures: Visualizing aging-associated heart diseases through a new lens.

Jasvinder Singh Bhatti, Naina Khullar, Rajesh Vijayvergiya, Umashanker Navik, Gurjit Kaur Bhatti, P Hemachandra Reddy.

  Aging bears many hard knocks, but heart disorders earn a particular allusion, being the most widespread. Cardiovascular diseases (CVDs) are becoming the biggest concern to mankind due to sundry health conditions directly or indirectly related to heart-linked abnormalities. Scientists know that mitochondria play a critical role in the pathophysiology of cardiac diseases. Both environment and genetics play an essential role in modulating and controlling mitochondrial functions. Even a minor abnormality may prove detrimental to heart function. Advanced age combined with an unhealthy lifestyle can cause most cardiomyocytes to be replaced by fibrotic tissue which upsets the conducting system and leads to arrhythmias. An aging heart encounters far more heart-associated comorbidities than a young heart. Many state-of-the-art technologies and procedures are already being used to prevent and treat heart attacks worldwide. However, it remains a mystery when this heart bomb would explode because it lacks an alarm. This calls for a novel and effective strategy for timely diagnosis and a sure-fire treatment. This review article provides a comprehensive overture of prospective potentials of mitochondrial miRNAs that predict complicated and interconnected pathways concerning heart ailments and signature compilations of relevant miRNAs as biomarkers to plot the role of miRNAs in epigenomics. This article suggests that analysis of DNA methylation patterns in age-associated heart diseases may determine age-impelled biomarkers of heart disease.

Keywords:  Cardiovascular diseases; Epigenomics; Fibrosis; Mitochondrial miRNA

DOI:  https://doi.org/10.1016/j.arr.2023.101882
Aging Pathobiol Ther. 2022 ;4(4): 129-131

Targeting IGF1R signaling for brain aging and Alzheimer's disease.

Joo Young Park, Martin Darvas, Warren Ladiges.

  The role of IGF1R signaling in the brain and its relationship to aging and neurological dysfunction is controversial. Because it was shown that low IGF1R activity consistently improved myocardial bioenergetics and function in hearts from aging mice, but not hearts from young mice, it was of interest to investigate this relationship in brain aging. We used CRISPR technology to develop a mouse model with targeted replacement of mouse IGF1R with the equivalent of the human R407H (IGF1RR407H) variant enriched in centenarians with a reduction in IGF1R protein activity. Middle-aged mice show improved cognitive performance thus possibly modeling IGF1R signaling in the aging brain, similar to what was reported in the aging heart. Because Alzheimer's disease (AD) is an age-related disease, specific IGF1RR407H pathways could be therapeutic targets in mice with AAV vector-based AD as well as for overall brain aging.

Keywords:  Alzheimer’s disease; IGF1R signaling; IGF1RR407H variant; brain aging; cognition

DOI:  https://doi.org/10.31491/apt.2022.12.103
Curr Opin Cardiol. 2023 Jan 31.

Are serum uric acid levels predictors of cardiovascular risk? An update.

Michael Georgoulis, Dimitri P Mikhailidis, Demosthenes B Panagiotakos.

PURPOSE OF REVIEW: The aim of this review was to update the evidence regarding the link between serum uric acid and cardiovascular risk, as well as the role of nutrition in the prevention and management of hyperuricaemia.RECENT FINDINGS: The review focuses on recent epidemiological evidence concerning the role of elevated serum uric acid levels in cardiovascular risk prediction. The dietary prevention and management of hyperuricaemia is also discussed with an emphasis on the adoption of prudent dietary patterns.
SUMMARY: There is evidence supporting that elevated serum uric acid levels are positively associated with cardiovascular disease risk and might represent a useful additional marker for risk stratification. The association of serum uric acid with all-cause and cardiovascular mortality seems to be U-shaped, suggesting that both very low and very high serum uric acid levels might be detrimental for survival, the former being mediated by malnutrition. Apart from medication, the dietary management of hyperuricaemia should focus on the adoption of a prudent dietary pattern, such as the Mediterranean diet, which can both prevent gout and mitigate cardiometabolic risk.

DOI: https://doi.org/10.1097/HCO.0000000000001029
Trends Hear. 2023 Jan-Dec;27:27 23312165231156412

Plasticity After Hearing Rehabilitation in the Aging Brain.

Diane S Lazard, Keith B Doelling, Luc H Arnal.

  Age-related hearing loss, presbycusis, is an unavoidable sensory degradation, often associated with the progressive decline of cognitive and social functions, and dementia. It is generally considered a natural consequence of the inner-ear deterioration. However, presbycusis arguably conflates a wide array of peripheral and central impairments. Although hearing rehabilitation maintains the integrity and activity of auditory networks and can prevent or revert maladaptive plasticity, the extent of such neural plastic changes in the aging brain is poorly appreciated. By reanalyzing a large-scale dataset of more than 2200 cochlear implant users (CI) and assessing the improvement in speech perception from 6 to 24 months of use, we show that, although rehabilitation improves speech understanding on average, age at implantation only minimally affects speech scores at 6 months but has a pejorative effect at 24 months post implantation. Furthermore, older subjects (>67 years old) were significantly more likely to degrade their performances after 2 years of CI use than the younger patients for each year increase in age. Secondary analysis reveals three possible plasticity trajectories after auditory rehabilitation to account for these disparities: Awakening, reversal of deafness-specific changes; Counteracting, stabilization of additional cognitive impairments; or Decline, independent pejorative processes that hearing rehabilitation cannot prevent. The role of complementary behavioral interventions needs to be considered to potentiate the (re)activation of auditory brain networks.

Keywords:  aging; auditory loss; cochlear implant; cognitive decline; presbycusis

DOI:  https://doi.org/10.1177/23312165231156412