A Review: Multi-Omics Approach to Studying the Association between Ionizing Radiation Effects on Biological Aging
3.1. Hallmarks and Indicators
Genomic Instability: At the core of aging lies genomic instability, characterized by accumulating DNA damage and mutations over time. Recent advances in genomics have unveiled a plethora of genes intricately involved in DNA repair and maintenance. Notable genes such as P16, P21, FOXO1, P53, SIRT1, SIRT6, TNFa, IL6, TFAM, GATA6, ALOX15B, MAOA, TSC1, mTOR, RIPK1, RIPK3, and MLKL have emerged as central players in safeguarding genomic integrity. Moreover, modern technologies like next-generation sequencing have empowered researchers to explore the genomic landscape of aging with unprecedented precision, uncovering novel genetic factors and intricate pathways contributing to the aging process.
Telomere Attrition: Telomeres, the protective caps at the ends of chromosomes, erode with each cell division, serving as a cellular countdown clock. Recent breakthroughs in telomere biology have unveiled the roles of telomerase and shelterin complex proteins in preserving telomere length and stability. The identification of genetic and epigenetic factors influencing telomere maintenance has illuminated potential avenues for interventions to counteract telomere attrition and extend cellular lifespan.
Epigenetic Alterations: Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the underlying DNA sequence, plays a pivotal role in aging. Recent research has spotlighted DNA methylation as a prominent epigenetic marker of aging. Advances in epigenome-wide association studies (EWASs) have identified specific methylation patterns associated with aging, paving the way for the development of epigenetic clocks that accurately estimate an individual’s biological age. MicroRNA research, while promising, remains an area ripe for further exploration to harness its full potential in unraveling the epigenetic intricacies of aging.
Loss of Proteostasis: Maintenance of proteostasis, i.e., the balance between protein synthesis, folding, and degradation, is essential for cellular health. Recent studies have highlighted the roles of chaperones, autophagy, and the ubiquitin–proteasome system in maintaining proteostasis. Advancements in proteomic techniques have enabled the identification of specific protein aggregates and misfolded proteins associated with age-related diseases, shedding light on potential therapeutic targets to mitigate proteostatic decline.
Deregulated Nutrient Sensing: The deregulation of nutrient-sensing pathways, including insulin and mTOR signaling, contributes to aging-related metabolic dysfunction. Recent research has elucidated the roles of genes like FOXO, AMPK, and SIRT1 in nutrient sensing and longevity. Additionally, proteomic studies have unveiled key proteins involved in nutrient-sensing pathways, providing insights into their intricate regulation and potential interventions to modulate nutrient sensing in aging.
Mitochondrial Dysfunction: Mitochondria, the cellular powerhouses, play a pivotal role in aging through their influence on energy production and the generation of reactive oxygen species (ROS). Recent advancements in mitochondrial research have unveiled the intricate mechanisms underlying mitochondrial dysfunction, including mitochondrial DNA mutations and impaired electron transport chain activity. Novel mitochondrially targeted therapies and antioxidants hold promise in mitigating the age-associated decline in mitochondrial function.
Cellular Senescence: Cellular senescence, characterized by irreversible cell cycle arrest, contributes to aging-related tissue dysfunction. Recent discoveries have illuminated the roles of the senescence-associated secretory phenotype (SASP) and specific senescence-inducing genes in driving senescence-related inflammation and tissue deterioration. Proteomic investigations have identified key SASP components, offering potential targets to modulate the detrimental effects of cellular senescence.
Stem Cell Exhaustion: Stem cell exhaustion, a hallmark of aging, limits tissue regeneration and repair. Recent advances in stem cell biology have unraveled the genetic and epigenetic mechanisms governing stem cell function. Techniques such as single-cell RNA sequencing have provided insights into the heterogeneity of stem cell populations and their responses to aging-related cues. Strategies to rejuvenate or replace exhausted stem cells hold promise for rejuvenation therapies.
Altered Intercellular Communication: Age-related changes in intercellular communication through factors like cytokines and growth factors contribute to aging-related pathologies. Recent studies have unveiled the roles of specific genes and pathways in mediating intercellular communication in aging. Proteomic approaches have identified key signaling molecules and their dysregulation in aging-related diseases, offering potential avenues for targeted interventions.
In addition to these hallmarks, metabolomics has emerged as a burgeoning field poised to provide comprehensive insights into the metabolic changes associated with aging and age-related diseases. Metabolomic profiling, combined with genetic, epigenetic, and proteomic data, promises a holistic understanding of the aging process, enabling the identification of biomarkers and therapeutic targets to enhance healthy aging and extend lifespan.
3.2. Overlapping Health Concerns
The intricate interplay between aging, radiation exposure, and associated health concerns transcends age groups, encompassing individuals across the entire lifespan. Recent advancements in medical research have unveiled trends and disparities in the impact of aging and radiation on health, shedding light on varying susceptibilities and implications in both young and older populations. Here, we delve into the multifaceted relationship between aging, radiation exposure, and age-related diseases, emphasizing trends observed in different age groups and incorporating relevant citations.
3.3. Estimating Biological Age
Associating oxidative stress with age presents a complex challenge, primarily because defining age as a baseline reference point is not straightforward. Chronological age, representing the number of years an individual has lived, is an uncontrollable factor that cannot be influenced to observe the effects of stressors. In contrast, biological age, which reflects an individual’s overall health and physiological state, cannot be directly measured or independently estimated. To navigate this complexity, researchers have developed gold standards for estimating biological age, aiming to bridge the gap between chronological and biological age.
Functional biomarkers encompass both cognitive and physical aspects of an individual’s health. These biomarkers offer valuable insights into how well an individual’s mind and body are functioning. Within the cognitive realm, indicators such as memory, decision reaction time, and verbal fluency provide critical information about cognitive decline or preservation. On the physical front, biomarkers like grip strength, walking speed, and visual perception and measures like height, weight/BMI, and lung capacity offer insights into an individual’s physical vitality and resilience [101,102,103,104,105,106].
Physiological biomarkers delve into the state of an individual’s organs, tissues, and cellular health. These biomarkers provide a deeper understanding of the body’s internal processes and can shed light on the effects of aging. Metrics such as brain size, blood composition, blood pressure, muscle mass, and bone density, among others, offer valuable data for assessing an individual’s physiological age [107,108].
Psychological well-being biomarkers are a unique category that delves into an individual’s emotional and mental state. This category is further divided into hedonic and eudaimonic dimensions. Hedonic aspects focus on happiness, subjective well-being, and positive emotions, while eudaimonic dimensions include self-acceptance, environmental mastery, positive relationships, personal growth, purpose in life, and autonomy. These biomarkers offer insights into an individual’s psychological resilience and overall well-being, which can influence their biological age [112,113].
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