As our understanding of the aging process deepens, researchers have uncovered an array of cellular and molecular changes that appear to accumulate over time and contribute to the physical and cognitive decline we associate with getting older. These changes, commonly referred to as the “hallmarks of aging,” were initially identified in 2013 to organize the many factors that contribute to aging and age-related diseases. However, ongoing scientific research has brought even more insights into this complex and multifaceted phenomenon.
In 2013, a set of nine signs of aging was initially identified by scientists. Since then, researchers have expanded this list to include three different biological processes contributing to aging. While each hallmark may impact signs of aging independently, there are often interconnections between them through various mechanisms.
Strategies for Promoting Healthy Aging and Longevity
Understanding the factors contributing to aging is crucial for developing strategies to slow aging and improve overall health in later life. By exploring mechanisms such as genomic instability, telomere shortening and stem cell exhaustion. We can gain insight into how aging occurs at the cellular level and identify potential targets for intervention. These 12 hallmarks offer a roadmap for understanding the complex aging process and provide a foundation for developing new approaches to promote healthy aging.
1: Nucleotide Diversity
Nucleotide diversity is characterized by an increased susceptibility of genetic material to changes or damage. The changes can be due to internal factors, such as errors during DNA replication and oxidative stress, or external factors, such as exposure to toxins, radiation, or other environmental stresses.
As cells age, they become less efficient at repairing DNA damage. That can exacerbate nucleotide diversity, leading to the accumulation of mutations and other alterations in the DNA sequence. These changes can have significant implications for health and disease, as they may disrupt normal cellular processes and contribute to the development of various disorders, including cancer.
2: Telomere Degradation
Telomeres are a crucial component of chromosome structure that plays a vital role in maintaining genetic stability and integrity. Small caps at the ends of chromosomes shorten with each cell division due to incomplete replication during DNA synthesis. As telomeres shorten, the protection for chromosomes decreases, eventually leading to cellular senescence or programmed cell death.
Studies have shown that telomere shortening can accelerate the aging process and contribute to the development of age-related diseases such as cardiovascular disease, cancer and neurodegenerative disorders. Additionally, telomere attrition has been linked to chronic inflammation, which can adversely affect cell functions and spread the senescence phenotype to surrounding cells.
Factors such as oxidative stress, inflammation and exposure to toxins can contribute to telomere attrition. However, regular aerobic exercise has been found to improve telomere length by increasing telomerase activity, an enzyme that adds telomere sequences to the ends of chromosomes. This suggests that exercise may have anti-aging benefits and help to prevent age-related diseases.
3: Altered Epigenetic Marks
Altered epigenetic marks refer to changes in gene expression regulation that are not caused by changes in the DNA sequence itself. Various factors can influence these alterations, including environmental exposures, diet, lifestyle choices and stress management.
Overtime, these epigenetic changes can become more pronounced, leading to undesirable changes in gene expression that may contribute to the development of age-related diseases and conditions. A recent review published in the International Journal of Molecular Sciences has identified Altered epigenetic marks as a potential contributor to several human pathologies, such as cancer, diabetes, osteoporosis and neurodegenerative disorders.
The good news is that Altered epigenetic marks are largely reversible and we can take steps to protect our genes from developing diseases. By controlling our environment, diet, lifestyle choices and stress management, we can reduce our risk of developing Altered epigenetic marks that can lead to disease.
4: Accumulation of Misfolded Proteins
The proper functioning of cells relies on maintaining homeostasis, which is regulated by proteostasis. This involves a delicate balance between protein synthesis, folding and degradation, critical for ensuring cellular function and preventing the accumulation of damaged or misfolded proteins. However, the ability of cells to maintain proteostasis declines over time. It can result in the accumulation of abnormal proteins associated with aging and disease.
One of the key pathological features observed in various neurodegenerative diseases is the formation of aggregated proteins within cells, which can disrupt cellular function and ultimately lead to cell death. Researchers have therefore suggested that maintaining proteostasis could be a potential therapeutic strategy for treating these diseases.
5: Disturbed Nutrient Homeostasis
The ability of cells to sense and respond to the availability of nutrients is essential for maintaining proper cellular metabolism, energy balance and growth. This process is referred to as nutrient sensing and when it becomes deregulated. The cell’s ability to sense the nutrients present is impaired. As a result, cellular mechanisms cannot occur efficiently.
One of the most critical nutrient-sensing pathways is regulated by insulin and insulin-like growth factor (IGF-1). This pathway has been shown to play a crucial role in regulating signs of aging and age-related diseases in model organisms.
Intermittent fasting is a popular dietary intervention that works through this pathway and is beneficial in animal models. However, further research is required to understand the role of this pathway in human aging and age-related diseases conclusively.
6: Mitochondrial impairment
Mitochondria are essential organelles within cells that generate energy in the form of ATP. This energy is crucial for proper functioning of cells, tissues and organs. Furthermore, mitochondria are involved in cellular metabolism.
When mitochondria fail to function correctly, they can lead to an increase in reactive oxygen species. It can trigger inflammation and oxidative stress. This can have harmful effects on cells and accelerate the signs of aging. Research has shown that mitochondrial dysfunction is associated with various human diseases, including cancer, cardiovascular disease and metabolic disorders.
7: Senescence-associated Secretory Phenotype (SASP)
As we age the cells in our body continue to divide but eventually many of them reach a point of senescence. This means they can no longer divide but remain metabolically active. While senescent cells can be beneficial in recruiting tissue repair factors to damaged areas or repairing cancerous cells. They can also become a burden as they accumulate over time.
The accumulation of senescent cells, sometimes called “zombie” cells, can contribute to chronic inflammation and age-related diseases. This process is known as “inflammaging.” Various stressors can trigger senescence, including telomere shortening, reactive oxygen species and potential epigenetic alterations that can activate cancerous cells.
Therefore, finding ways to prevent or remove accumulated senescent cells to maintain good health and avoid age-related diseases is essential. Researchers are exploring various strategies, including senolytic drugs that selectively target and eliminate senescent cells. And lifestyle modifications such as exercise and a healthy diet that can delay or prevent the onset of senescence.
8: Stem Cell Quiescence
Stem cells are crucial in maintaining tissue function and promoting tissue regeneration. Factors such as DNA damage, telomere shortening, oxidative stress and epigenetic changes can lead to stem cell exhaustion and a decline in their regenerative abilities. This decline in stem cell function may contribute to age-related diseases, including neurodegenerative diseases, cardiovascular diseases and cancer. Failure to respond appropriately to DNA damage can also increase the risk of cancer initiation and progression.
9: Altered Intercellular Communication
As previously stated, “Within an organism, such as the human body, all functions are interconnected and interdependent. Cells communicate through various mechanisms and any disruption to this communication can result in the loss, misinterpretation, or ignorance of signals, ultimately affecting tissue function and repair. Such disruptions may also contribute to the development of age-related diseases.”
10: Inflammation That Persists Over Time
“Described as a subtle yet persistent inflammatory process, inflammaging can devastate the body over time. It’s similar to being pricked by a small needle repeatedly – at first, the sensation may go unnoticed. But with the passing of days, weeks, months and years, the damage accumulates and becomes more pronounced. In addition to molecular inflammation, recent research has identified complex networks of inflammation and proinflammatory pathways. That contribute to the aging process and worsen age-related chronic diseases at a systemic level.”
11: Arrested Macroautophagy
Autophagy, or macroautophagy, is a crucial natural process that enables cells to eliminate dysfunctional proteins and organelles, promoting cellular balance. However, aging, mitochondrial dysfunction, oxidative stress and epigenetic factors can impair this process. Causing the accumulation of damaged cells and proteins and accelerating the aging process. Moreover, the disruption of autophagy has been linked to several serious illnesses, including type 2 diabetes, Alzheimer’s disease and cardiovascular disease.
12: Microbial Dysregulation
Microbial dysregulation is a term used to describe an imbalance in the gut microbiota, which has become the focus of numerous studies in recent years due to its critical role in human health. The gut microbiome, consisting of trillions of microorganisms, is a complex ecosystem essential for human health.
Research has shown that the gut microbiome is vital in many physiological activities necessary for human development and health. Furthermore, dysbiosis can lead to adverse health outcomes, accelerate signs of aging and increase systemic inflammation. Which is one of the hallmarks of aging.
Additionally, when the symbiotic relationship between our cells and gut microbes becomes disrupted. The microbial community within the gut can become a source of infection, leading to various age-related diseases. Such as obesity, diabetes, inflammatory bowel disease, allergies and neurological disorders like depression and Alzheimer’s disease.
Aging is a complicated process still being studied in animal and human models. But understanding these twelve hallmarks could lead to interventions that slow or reverse the signs of aging process and improve health span.
