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Basic Science of Aging: Immediate Applications of Aging Research to Medicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 3935

Special Issue Editor

Dr. Shin Murakami

E-Mail Website
Guest Editor
Department of Foundational Biomedical Sciences, College of Osteopathic Medicine, Touro University California, Vallejo, CA, USA
Interests: biology of aging; gerontology; geriatrics; stress resistance; dementia; age-related comorbidities; risk assessment; artificial intelligence; systems biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The focus of this Special Issue is on developing our understanding of genetics and systems’ biological mechanisms regarding aging and health. The objective is to advocate basic scientific research that emphasizes a molecular understanding of aging, with potential immediate application to medicine and the community.

Aging causes vulnerability to age-related comorbidities, including hypertension, diabetes, cardiovascular diseases and more recently COVID-19 severity, among others. A wide variety of genetic, nutritional and pharmacological interventions have been known to promote health and increase lifespans in the model systems. However, how these interventions can be applied to medicine has yet to be adequately explored. A collection of heritable knowledge with potential immediate impacts on medicine is expected to provide effective ways to promote health spans. Partial starvation, for example, “Hara Hachi Bun Me (Eat until 80% full)”, is an ancient intervention for health. Metformin, a classic diabetes drug, is under a clinical trial known as the TAME (Targeting Aging with Metformin) trial, (Barzilai et al., 2016). The angiotensin-converting enzyme (ACE) gene is a first-line drug target for the treatment of hypertension, while ACE inhibitors can extend lifespans in the model systems (Le et al., 2021). This Special Issue also emphasizes the systems biology of the genes involved in life-extending interventions, as well as biological processes including lipid metabolism, inflammation and protein-degrading mechanisms, among others. These genes may be involved in multiple neurological problems such as amyotrophic lateral sclerosis, Multiple Sclerosis, Parkinson's disease, and schizophrenia (Vahdati Nia et al., 2017). We would also like to invite a collection of biomedical knowledge toward the middle-life crisis theory of aging, which explains the transition from young to old. 

Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016 Jun 14;23(6):1060-1065. doi: 10.1016/j.cmet.2016.05.011. PMID: 27304507; PMCID: PMC5943638. https://pubmed.ncbi.nlm.nih.gov/27304507/

Le D, Brown L, Malik K, Murakami S. Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging. Int J Mol Sci. 2021 Dec 7;22(24):13178. doi: 10.3390/ijms222413178. PMID: 34947975; PMCID: PMC8707689. https://pubmed.ncbi.nlm.nih.gov/34947975/

Vahdati Nia B, Kang C, Tran MG, Lee D, Murakami S. Meta Analysis of Human AlzGene Database: Benefits and Limitations of Using C. elegans for the Study of Alzheimer's Disease and Co-morbid Conditions. Front Genet. 2017 May 12;8:55. doi: 10.3389/fgene.2017.00055. PMID: 28553317; PMCID: PMC5427079. https://pubmed.ncbi.nlm.nih.gov/28553317/

Prof. Dr. Shin Murakami
Guest Editor

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Keywords

  • model systems
  • humans
  • genes
  • miRNA
  • systematic review and meta-analysis
  • genome-wide association studies (GWAS)
  • molecular mechanisms
  • dyslipidemia
  • hypertension

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Published Papers (2 papers)

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14 pages, 5522 KiB  
Article
Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals
by Lingxuan Li and Shin Murakami
Int. J. Mol. Sci. 2023, 24(4), 3411; https://doi.org/10.3390/ijms24043411 - 8 Feb 2023
Cited by 3 | Viewed by 1521
Abstract
Current research on the angiotensin-converting-enzyme (ACE) gene has yielded controversial results on whether different ACE polymorphisms are linked with human longevity. ACE polymorphisms are a risk factor for Alzheimer’s disease and age-onset diseases that may contribute to the mortality of older [...] Read more.
Current research on the angiotensin-converting-enzyme (ACE) gene has yielded controversial results on whether different ACE polymorphisms are linked with human longevity. ACE polymorphisms are a risk factor for Alzheimer’s disease and age-onset diseases that may contribute to the mortality of older people. Our goal is to consolidate existing studies, using artificial intelligence-assisted software to come to a more precise understanding of the role of the ACE gene in human longevity. The I (insertion) and D (deletion) polymorphisms in the intron are correlated with the levels of circulating ACE; homozygous D (DD) is high, and homozygous I (II) is low. Here, we performed a detailed meta-analysis of the I and D polymorphisms using centenarians (100+ years old), long-lived subjects (85+ years old), and control groups. ACE genotype distribution was analyzed across a total of 2054 centenarians and 12,074 controls, as well as 1367 long-lived subjects between the ages of 85–99, using the inverse variance and random effects methods. The ACE DD genotype was found to be favored in centenarians (OR: 1.41 (95% CI: 1.19–1.67), p < 0.0001) with a heterogeneity of 32%, and the II genotype slightly favored the control groups (OR: 0.81 (95% CI: 0.66–0.98), p = 0.03) with a heterogeneity of 28%, corroborating results from previous meta-analyses. Novel to our meta-analysis, the ID genotype was found to be favored in control groups (OR: 0.86 (95% CI: 0.76–0.97), p = 0.01) with a heterogeneity of 0%. The long-lived group showed a similar positive association between the DD genotype and longevity (OR: 1.34 (95% CI: 1.21–1.48), p < 0.0001) and a negative association between the II genotype and longevity (OR: 0.79 (95% CI: 0.70–0.88), p < 0.0001). The long-lived ID genotype did not show significant findings (OR: 0.93 (95% CI: 0.84–1.02), p = 0.79). In conclusion, the results suggest a significant positive association of the DD genotype with human longevity. However, despite the previous study, the results do not confirm a positive association of the ID genotype with human longevity. We suggest a few important paradoxical implications: (1) inhibition of ACE can increase longevity in model systems from nematodes to mammals, seemingly opposite to the finding in humans; (2) exceptional longevity associated with homozygous DD is also associated with age-related diseases with higher mortality risks in homozygous DD. We discuss ACE, longevity, and age-related diseases. Full article
(This article belongs to the Special Issue Basic Science of Aging: Immediate Applications of Aging Research to Medicine)
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17 pages, 4327 KiB  
Article
Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses
by Lulu Tan, Xiakeerzhati Xiaohalati, Feng Liu, Jia Liu, Haoyu Fu, Yang Zhang, Jinbo Gao, Kaixiong Tao, Guobin Wang, Lin Wang and Zheng Wang
Int. J. Mol. Sci. 2023, 24(2), 1516; https://doi.org/10.3390/ijms24021516 - 12 Jan 2023
Cited by 2 | Viewed by 2075
Abstract
Colorectal cancer (CRC) is critically related to aging and severely threatens human lives. To better explore the effects of aging on CRC progression and therapy outcome, a reliable aging subtypes identification of CRC is urgently desired. Here, 28 aging-related genes associated with the [...] Read more.
Colorectal cancer (CRC) is critically related to aging and severely threatens human lives. To better explore the effects of aging on CRC progression and therapy outcome, a reliable aging subtypes identification of CRC is urgently desired. Here, 28 aging-related genes associated with the CRC prognosis were selected by univariate Cox analyses. Based on these 28 genes, CRC patients were divided into the aging subtype and young subtype by non-negative matrix factorization clustering. Aging subtype and young subtype of CRC were identified with distinct molecular features and clinical prognosis. The aging subtype was characterized by upregulation of senescence-associated secretory phenotype, higher frequencies of TP53 and immune checkpoint molecules, and high sensitivity to protein kinase and angiogenesis inhibitors. Furthermore, 14 genes were selected by LASSO penalized Cox regression analyses for aging-related risk signature construction. The constructed aging risk signature exhibited good prediction and the nomogram showed robust discrimination power over the traditional CRC staging system. In conclusion, this study successfully established aging subtype and young subtype of CRC, which is helpful to identify patients with aging characteristics to evaluate prognosis and treatment outcomes. Introducing aging-based subtypes into clinical concern and patient prognostication provides new opportunities for personalized CRC treatment. Full article
(This article belongs to the Special Issue Basic Science of Aging: Immediate Applications of Aging Research to Medicine)
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