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Review
. 2024 Mar 28:5:1373741.
doi: 10.3389/fragi.2024.1373741. eCollection 2024.

Decoding the secrets of longevity: unraveling nutraceutical and miRNA-Mediated aging pathways and therapeutic strategies

Rania M Salama  1 , Nermin Eissa  2 , Ahmed S Doghish  3   4 , Ahmed I Abulsoud  4   5 , Nourhan M Abdelmaksoud  5 , Osama A Mohammed  6 , Sherif S Abdel Mageed  7 , Samar F Darwish  7
Affiliations
Review

Decoding the secrets of longevity: unraveling nutraceutical and miRNA-Mediated aging pathways and therapeutic strategies

Rania M Salama et al. Front Aging. .

Abstract

MicroRNAs (miRNAs) are short RNA molecules that are not involved in coding for proteins. They have a significant function in regulating gene expression after the process of transcription. Their participation in several biological processes has rendered them appealing subjects for investigating age-related disorders. Increasing data indicates that miRNAs can be influenced by dietary variables, such as macronutrients, micronutrients, trace minerals, and nutraceuticals. This review examines the influence of dietary factors and nutraceuticals on the regulation of miRNA in relation to the process of aging. We examine the present comprehension of miRNA disruption in age-related illnesses and emphasize the possibility of dietary manipulation as a means of prevention or treatment. Consolidating animal and human research is essential to validate the significance of dietary miRNA control in living organisms, despite the abundance of information already provided by several studies. This review elucidates the complex interaction among miRNAs, nutrition, and aging, offering valuable insights into promising areas for further research and potential therapies for age-related disorders.

Keywords: age-related diseases; aging; miRNAs; nutraceuticals; nutrition.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
An overview of canonical and non-canonical pathways in miRNA biogenesis. In the canonical pathway, RNA Pol II transcribes the miRNA gene, and the microprocessor complex (Drosha and DGCR8) processes it to form a pre-miRNA. The non-canonical route is Drosha/DGCR8-independent and produces pre-miRNA directly from the entire intron. Both pathways converge as pre-miRNA is exported to the cytoplasm by EXP 5 and Ran-GTP. In the cytoplasm, Dicer processes pre-miRNA into a smaller double-stranded miRNA, which undergoes further cleavage to create a miRNA duplex. The duplex binds to Ago to form the RISC. The Ago-bound miRNA duplex unwinds, selecting either the 5p or 3p strand for the mature RISC complex. Ago, argonaute1; DGCR8, DiGeorge Critical Region 8; Dicer, an endoribonuclease enzyme that in humans is encoded by the DICER1 gene; Drosha, double-stranded RNA-specific endoribonuclease; EXP 5, Exportin-5; miRNA, microRNA; Ran, RAS-related nuclear protein; RISC, RNA-induced silencing complex; RNA Pol II, RNA polymerase II; TRBP, transactivation response element RNA-binding protein.
FIGURE 2
FIGURE 2
miRNA dysregulation in age-related diseases. Neurodegenerative and age-related disorders, including Alzheimer’s disease, cardiovascular conditions (hypertension, heart failure, and atherosclerosis), osteoarthritis, osteoporosis, and macular degeneration, are strongly associated with miRNA dysregulation. MicroRNAs are involved in disease etiology and may be biomarkers and therapeutic targets. Furthermore, miRNA dysregulation is crucial to understanding age-related diseases’ biological processes as well as personalized therapy. ACE: angiotensin-converting enzyme; ALK, anaplastic lymphoma kinase; AMPKs: AMP-activated protein kinases; BAI3, brain angiogenesis Inhibitor-3; ch, cholesterol; ECs, endothelial cells; HDL-C, high-density lipoprotein cholesterol; LDL, low-density lipoprotein; MACF1, Microtubule Actin Crosslinking Factor 1; miRNA, microRNA; NF-κB: nuclear factor kappa beta; RYK, receptor-like tyrosine kinase; TLR4: Toll-like receptor 4.
FIGURE 3
FIGURE 3
Nutritional factors and nutraceuticals’ role in miRNA regulation. The illustration depicts how nutrients and nutraceuticals modulate miRNAs in aging processes. MiRNA expression is influenced by macronutrients such as carbohydrates and fatty acids, as well as micronutrients like selenium and zinc, which impact aging and age-related diseases. Flavonoids and polyphenols in olive oil and grape seeds influence miRNA function in the fight against aging. Nutraceuticals, such as pistachios and probiotics, also affect miRNA expression, suggesting promising treatments for age-related diseases.
FIGURE 4
FIGURE 4
Molecular mechanisms underlying miRNA-mediated regulation of aging processes. This figure illustrates the molecular basis of miRNA-mediated control over aging, with a focus on nutrition-sensing pathways and aging-related signaling networks. Across various species, miRNAs play a crucial role in regulating lifespan and key aging mechanisms. Lifespan and age-related processes are governed by AMPK, Sirtuins, and the Insulin/IGF-1 signaling pathways. The interconnection between cell metabolism, stress response, and longevity is established through nutrient-sensing mechanisms such as mTOR and the IGF1/PI3K/AKT pathway. Diet affects miRNA modulation, highlighting the complex link between nutrition, molecular aging pathways, and lifespan regulation. A comprehensive understanding of the complex interplay between miRNAs and nutrient-sensing pathways can shed light on the causes of aging and identify potential drug targets. AGE, advanced glycation end products; Akt, protein kinase B; AMP, adenosine monophosphate; AMPKs, AMP-activated protein kinases; BDNF, brain-derived neurotrophic factor; ER, estrogen receptor; FOXO, Forkhead box protein O; HSP, heat shock protein; IGF-1, insulin-like growth factor-1; IGFR, insulin-like growth factor receptor; IRS, insulin receptor substrate; mTOR, mammalian target of rapamycin; mTORC, mTOR complex; NF-κB, nuclear factor kappa beta; PDK1, 3-phosphoinositide-dependent kinase 1; PGC1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PI3K, phosphoinositide-3-kinase; PIP2, phosphatidylinositol (4,5)-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; PRAS40, proline-rich Akt substrate of 40 kDa; PTEN, Phosphatase and Tensin Homolog; ROS, reactive oxygen species; SIRT1, Sirtuin 1; SOD, superoxide dismutase; TGF-β, Transforming growth factor β; TLR4, Toll-like receptor 4; TMAO, trimethylamine N-oxide; TrkB, Tropomyosin receptor kinase B; TSC, Tuberous sclerosis protein.
FIGURE 5
FIGURE 5
miRNA involvement in the therapeutic impact of nutraceuticals on aging and age-related diseases. Nutraceuticals rich in polyphenols and bioactive compounds exhibit anti-inflammatory and antioxidant effects, potentially enhancing cellular longevity and mitigating age-related changes. These compounds can influence miRNA expression, offering promising strategies for promoting healthy aging and preventing or treating age-related diseases. COX-2, cyclooxygenase 2; EGCG, epigallocatechin-3-gallate; H-EVOO, high-extra virgin olive oil; MAPKs, mitogen-activated protein kinases; NF-κB, nuclear factor kappa beta; ROS, reactive oxygen species; SIRT1, sirtuin 1.
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