July 28, 2023
Updated: 12 Hallmarks of Aging
The Evolving Science: A Comprehensive Guide to the 12 Hallmarks of Aging
Aging is a complex biological phenomenon that affects all living organisms. As we journey through life, our bodies undergo a series of changes at the cellular and molecular levels. Scientists have identified 12 fundamental hallmarks of aging, each contributing to the intricate tapestry of the aging process. In this article, we'll delve into these hallmarks to better understand the underlying mechanisms of aging and explore potential strategies to promote healthier aging and extend our vitality.
Learn about the Foundation of Aging
1. Genomic Instability: The Blueprint of Aging
At the heart of the aging process lies genomic instability—the gradual accumulation of DNA damage and mutations. We'll explore how these genetic disruptions impact cellular function and increase the risk of age-related diseases, particularly cancer.
2. Telomere Attrition: The Clockwork of Cellular Senescence
Discover how telomeres, the protective caps at the ends of our chromosomes, act as a biological clock that ticks away with each cell division. Learn about the connection between telomere shortening, cellular senescence, and the eventual decline of tissue regeneration.
3. Epigenetic Alterations: Rewriting the Story of Aging
Epigenetic changes influence how our genes are expressed without altering their underlying DNA sequence. We'll delve into the role of epigenetics in shaping the aging process and its impact on age-related diseases.
4. Loss of Proteostasis: The Decline in Cellular Cleanliness
Explore how the loss of proteostasis—cellular quality control—leads to the accumulation of misfolded proteins and impaired cellular function. Learn how this hallmark contributes to neurodegenerative diseases and other age-related disorders.
5. Impaired Macroautophagy: Spring Cleaning for Cellular Renewal
Macroautophagy, a process that clears out damaged cellular components, becomes less efficient with age. Discover its role in maintaining cellular health and how its dysfunction can accelerate the aging process.
6. Dysregulated Nutrient-Sensing: Balancing Energy and Longevity
Dive into the dysregulation of nutrient-sensing pathways and their impact on metabolism and energy regulation. We'll explore how these pathways influence the aging process and discuss potential interventions for healthier aging.
7. Mitochondrial Dysfunction: Energy Centers Gone Awry
Mitochondria, the powerhouses of our cells, play a crucial role in energy production. Learn how mitochondrial dysfunction contributes to the aging process and age-related diseases, and explore emerging research on mitochondrial-targeted therapies.
8. Cellular Senescence: Cells in Limbo
Uncover the phenomenon of cellular senescence, where cells cease to divide but remain metabolically active. Understand the role of senescent cells in promoting inflammation and tissue dysfunction, and learn about strategies to clear these cells.
9. Exhaustion of Stem Cells: The Fountain of Youth Runs Dry
Stem cells are essential for tissue repair and renewal, but their numbers and regenerative potential decline with age. We'll discuss the implications of stem cell exhaustion and explore approaches to rejuvenate these vital cells.
10. Altered Intercellular Communication: Disrupted Conversations
Communication between cells is essential for maintaining tissue homeostasis. Discover how dysregulated intercellular communication contributes to the aging process and learn about potential interventions to restore effective cell signaling.
11. Chronic Inflammation: Inflammaging Takes Center Stage
Explore the concept of "inflammaging" and its role in driving various age-related diseases. We'll delve into the relationship between chronic inflammation, cellular damage, and strategies to mitigate its effects.
12. Dysbiosis: Gut Health and Aging
Uncover the importance of a balanced gut microbiota in healthy aging. Learn how dysbiosis, an imbalance in gut bacteria, can impact digestion, immune function, and overall well-being.
The 12 hallmarks of aging provide a comprehensive framework for understanding the intricate processes that shape our journey through life. As we unravel the secrets of aging, we gain insights into potential interventions and strategies to promote healthier aging and enhance our quality of life. By embracing the knowledge presented in this article, we can navigate the aging process with greater understanding and make informed choices for a more vibrant future.
Lets Dive in Deeper
1. Genomic Instability: The Blueprint of Aging
At the heart of our biological makeup lies the blueprint of life: our DNA. Genomic instability, one of the fundamental hallmarks of aging, reflects the gradual accumulation of damage and mutations within our DNA over time. Imagine DNA as a delicate script that dictates the functions and characteristics of every living cell. However, as we journey through life, our DNA isn't immune to the effects of wear and tear.
External factors like ultraviolet radiation, environmental toxins, and even the natural processes of DNA replication can cause errors to occur within our genetic code. These errors can manifest as changes in the sequence of nucleotides that make up our DNA, leading to mutations. While our cells have repair mechanisms to fix such errors, they aren't perfect, and some errors persist, contributing to genomic instability.
The consequences of genomic instability are far-reaching. Cells with damaged DNA may function abnormally or die, potentially compromising the health of the tissues and organs they compose. Moreover, mutations that accumulate over time can increase the risk of various age-related diseases, most notably cancer. Cancer often arises from cells with DNA mutations that cause uncontrolled growth and division.
As we age, the mechanisms that repair DNA damage become less efficient, leading to a higher likelihood of genomic instability. While the accumulation of DNA mutations is a natural part of the aging process, researchers are keen to understand how to minimize its impact. Exploring ways to enhance DNA repair mechanisms or prevent DNA damage in the first place is a crucial avenue for potential interventions to slow down the aging process and mitigate the risk of age-related diseases.
In essence, genomic instability serves as a reminder that our cells' very blueprints are vulnerable to the passage of time. By deciphering the intricacies of DNA maintenance and repair, scientists aim to unlock new strategies for promoting healthy aging and extending the years of vitality.
2. Telomere Attrition: The Clockwork of Cellular Senescence
Imagine your chromosomes as shoelaces with protective caps at their ends. These caps are called telomeres, and they play a crucial role in preserving the integrity of our genetic material. Telomeres are like the ticking hands of a biological clock, gradually shortening with each cell division. This process is known as telomere attrition, and it is a hallmark of aging that holds profound implications for our cellular health.
Telomeres serve as guardians of our chromosomes, preventing them from fraying or sticking to other chromosomes. However, during each cell division, a portion of the telomere is lost, bringing our cells one step closer to their biological limit. When telomeres become critically short, cells enter a state of senescence—a state in which they cease to divide and function as they should. This phenomenon acts as a protective mechanism, preventing cells with damaged DNA from proliferating and potentially becoming cancerous. Yet, it also hampers our body's ability to renew and repair itself.
Cellular senescence, driven by telomere attrition, has significant consequences for the aging process. As tissues experience an increasing number of senescent cells, their ability to regenerate declines. This gradual loss of regenerative potential contributes to the weakening of organs and tissues over time, ultimately manifesting as the physical signs of aging.
However, research has shown that the rate of telomere attrition isn't solely determined by the passage of time. Lifestyle factors, including diet, stress, exercise, and sleep, can influence how quickly telomeres shorten. This implies that we might have a degree of control over this aging process. Scientists are actively exploring interventions to slow down telomere attrition, ranging from dietary adjustments to stress management techniques.
By understanding the delicate balance between telomere attrition and cellular senescence, researchers are aiming to develop strategies that promote healthier aging. While the biological clock of telomeres continues to tick, the knowledge gained from studying this hallmark may allow us to adjust its pace and extend the vitality of our cells.
3. Epigenetic Alterations: Rewriting the Story of Aging
In the intricate tale of our DNA, there's more than just the sequence of A's, T's, C's, and G's. Epigenetics reveals the dynamic layer of information that guides how genes are turned on or off, dictating our cellular function and ultimately influencing the aging process. Epigenetic alterations, a hallmark of aging, involve changes in these gene expression patterns without altering the underlying DNA sequence.
Imagine the DNA as a script, and epigenetic marks as highlights and annotations that determine which parts of the script are read and acted upon. With time, these annotations can become altered, leading to shifts in gene expression that contribute to the aging process. As certain genes that promote cellular health are turned off and others that drive inflammation are activated, the balance within our cells is disrupted.
The significance of epigenetic alterations lies not only in their influence on aging but also in their potential reversibility. Unlike mutations in the DNA sequence, which are difficult to repair, epigenetic modifications offer a promising avenue for intervention. Researchers are exploring ways to reset or rejuvenate these epigenetic marks, effectively rewiring the cellular script to promote more youthful function.
One area of focus is the use of epigenetic therapies, which involve manipulating these marks to restore youthful gene expression patterns. This approach has shown promise in preclinical studies, rejuvenating aged cells and tissues and delaying age-related decline. Additionally, lifestyle factors such as diet, exercise, and stress management have been linked to epigenetic changes, highlighting the importance of adopting a holistic approach to healthy aging.
Understanding the intricate dance between our genes and their epigenetic marks offers a new perspective on aging—one that goes beyond the fixed blueprint of our DNA. By rewriting the epigenetic story, researchers aim to unlock the potential to promote not only a longer life but a higher quality of life, as cells retain their youthful vitality and function.
4. Loss of Proteostasis: The Decline in Cellular Cleanliness
Imagine your cells as bustling factories, constantly producing proteins that carry out essential tasks. To maintain proper function, these proteins need to be folded correctly, much like origami pieces crafted with precision. The intricate process of protein folding and maintenance is known as proteostasis. However, with the passage of time, this cellular cleaning system can falter, leading to a hallmark of aging: the loss of proteostasis.
Think of proteins as workers on an assembly line. Just as a misfolded piece of machinery can disrupt the entire production process, misfolded proteins can wreak havoc within cells. In youthful cells, quality control mechanisms ensure that misfolded proteins are promptly identified and either refolded or degraded. Yet, as we age, this quality control machinery becomes less efficient, allowing misfolded proteins to accumulate.
The buildup of misfolded proteins poses multiple threats. It can impair cellular function, leading to a decline in overall tissue health. Furthermore, these aggregates can trigger inflammation and stress responses that exacerbate the aging process. In neurodegenerative diseases like Alzheimer's and Parkinson's, the accumulation of misfolded proteins is particularly problematic, contributing to the gradual breakdown of cognitive and motor functions.
Addressing the loss of proteostasis offers exciting opportunities for intervention. Researchers are exploring ways to enhance the cellular machinery responsible for protein folding and degradation. Additionally, compounds that promote protein clearance, such as autophagy-inducing substances, are being investigated as potential therapies for age-related diseases.
Maintaining the cellular cleanliness of proteostasis is crucial for vibrant aging. Just as a clean and organized workspace leads to efficient productivity, cells that effectively manage protein quality contribute to the overall health and longevity of our bodies. By understanding the mechanisms behind the loss of proteostasis, scientists are uncovering strategies to prevent the accumulation of cellular clutter and extend the functionality of our cells well into our later years.
5. Impaired Macroautophagy: Spring Cleaning for Cellular Renewal
Imagine your cells as bustling cities, each with their own streets and buildings. Just as cities need regular maintenance to function smoothly, cells require constant cleaning and renewal to stay healthy. This maintenance process is orchestrated by a cellular mechanism known as macroautophagy, often referred to as the cell's "spring cleaning" process. However, as time goes on, this process can become less efficient, contributing to the aging process.
Macroautophagy involves the removal and recycling of damaged cellular components, ensuring that the cell remains free from waste and clutter. Picture it as garbage trucks patrolling the streets, collecting and recycling old or dysfunctional materials. In youthful cells, this process is highly effective, allowing cells to maintain their vitality and functionality. But as we age, the efficiency of macroautophagy can decline, leading to the accumulation of cellular debris.
The consequences of impaired macroautophagy are significant. Accumulated cellular waste can hinder cellular function and contribute to the development of age-related diseases, including neurodegenerative conditions like Alzheimer's and Parkinson's. Additionally, the buildup of damaged components can trigger inflammation and cellular stress responses, further accelerating the aging process.
Researchers are actively investigating ways to boost macroautophagy and restore cellular renewal. Caloric restriction and intermittent fasting are among the strategies that have shown potential in enhancing this process. Additionally, certain compounds and drugs are being explored as potential interventions to stimulate macroautophagy and promote healthy aging.
Just as a well-maintained city thrives with efficient waste management systems, cells that engage in effective macroautophagy enjoy enhanced functionality and longevity. By understanding the mechanisms behind impaired macroautophagy, scientists are uncovering ways to rejuvenate cellular spring cleaning and pave the way for a more vibrant and youthful aging process.
6. Dysregulated Nutrient-Sensing: Balancing Energy and Longevity
Picture your body as a finely tuned machine that relies on a delicate balance of nutrients to function optimally. This balance is regulated by intricate nutrient-sensing pathways, which play a vital role in metabolism, energy regulation, and ultimately, the aging process. However, with the passage of time, these pathways can become dysregulated, contributing to a hallmark of aging known as dysregulated nutrient-sensing.
Imagine these pathways as traffic signals that guide the flow of nutrients within your cells. In a youthful body, these signals ensure that nutrients are allocated appropriately to support energy production, growth, and repair. However, as we age, these signals can become disrupted, leading to imbalances in nutrient utilization. This dysregulation can lead to excess energy storage, metabolic dysfunction, and an increased risk of age-related diseases such as type 2 diabetes and cardiovascular conditions.
One of the primary nutrient-sensing pathways is the insulin signaling pathway, which helps regulate glucose uptake and utilization. Another important pathway involves the mammalian target of rapamycin (mTOR), which senses nutrient availability and influences cell growth and proliferation. Dysregulation of these pathways can tip the balance between healthy metabolism and the onset of metabolic disorders.
Researchers are actively exploring interventions to restore nutrient-sensing balance and promote healthy aging. Caloric restriction, for instance, has been shown to enhance insulin sensitivity and extend lifespan in various organisms. Additionally, certain compounds and dietary supplements are being investigated for their potential to modulate nutrient-sensing pathways and promote longevity.
Just as a well-functioning traffic system ensures smooth movement, cells that maintain balanced nutrient-sensing pathways experience enhanced metabolic health and longevity. By unraveling the complexities of dysregulated nutrient-sensing, scientists aim to develop strategies that restore nutrient balance and promote healthy aging, allowing us to navigate the journey of life with vitality and well-being.
7. Mitochondrial Dysfunction: Energy Centers Gone Awry
Within the intricate landscape of our cells lies an essential powerhouse—the mitochondria. These microscopic energy factories are responsible for producing the energy required to fuel cellular processes. However, as the years go by, the efficiency of these powerhouses can diminish, giving rise to a hallmark of aging: mitochondrial dysfunction.
Imagine mitochondria as tiny generators, converting nutrients into energy through a process known as oxidative phosphorylation. Like any machinery, they generate not only energy but also waste products. Over time, the accumulation of these waste products can damage mitochondrial components, impairing their ability to produce energy and leading to a decline in overall cellular function.
The consequences of mitochondrial dysfunction are far-reaching. Reduced energy production affects the performance of every cell, tissue, and organ in our bodies. This decline in energy output not only impacts physical endurance but also makes cells more vulnerable to oxidative stress, accelerating the aging process. Moreover, dysfunctional mitochondria can release harmful molecules, contributing to inflammation and further exacerbating age-related diseases.
Mitochondrial dysfunction is particularly relevant to age-related conditions like neurodegenerative diseases and metabolic disorders. In Alzheimer's disease, for instance, brain cells are especially reliant on energy production, making them susceptible to mitochondrial dysfunction-induced damage.
Researchers are exploring ways to address mitochondrial dysfunction and its impact on aging. Emerging strategies include mitochondrial-targeted antioxidants and compounds that promote mitochondrial repair and function. Additionally, lifestyle factors such as regular exercise and a balanced diet have been linked to improved mitochondrial health.
Just as well-maintained generators power a city efficiently, cells with functional mitochondria enjoy sustained energy production and vitality. By uncovering the intricacies of mitochondrial dysfunction, scientists are paving the way for interventions that enhance cellular energy production and contribute to healthier aging, allowing us to maintain vigor and vitality as the years progress.
8. Cellular Senescence: Cells in Limbo
Imagine a bustling community of cells, each contributing to the harmony and function of your body. However, as time goes on, some cells enter a state of suspended animation—a phase known as cellular senescence. These cells no longer divide, yet they remain metabolically active, existing in a state of cellular limbo. This phenomenon, a hallmark of aging, has both protective and detrimental effects on the body.
Cellular senescence acts as a double-edged sword. On one hand, it prevents cells with damaged DNA from proliferating, guarding against the development of cancer. On the other hand, as more cells enter this state, the body's regenerative capacity declines. With fewer active cells available to replace damaged or lost ones, tissues and organs gradually lose their ability to function optimally.
One significant aspect of cellular senescence is its role in promoting inflammation. Senescent cells release molecules called cytokines and other inflammatory signals, collectively termed the senescence-associated secretory phenotype (SASP). While this inflammation is intended to attract immune cells for cellular cleanup, it can also contribute to chronic inflammation, a key driver of various age-related diseases.
The accumulation of senescent cells is associated with a wide range of age-related conditions, including cardiovascular disease, osteoarthritis, and neurodegenerative disorders. Researchers are actively exploring strategies to target and remove these senescent cells, a process known as "senolysis." By clearing senescent cells, researchers aim to reduce inflammation and improve tissue function, potentially extending healthspan and reducing the burden of age-related diseases.
In the realm of healthy aging, striking a balance between protecting against cancer and preserving tissue function is crucial. The study of cellular senescence offers a window into this delicate balance, shedding light on potential interventions that can enhance tissue regeneration, mitigate chronic inflammation, and promote overall well-being in the later stages of life.
9. Exhaustion of Stem Cells: The Fountain of Youth Runs Dry
Imagine stem cells as the architects of the body, responsible for creating and maintaining its various structures. These versatile cells possess the remarkable ability to differentiate into specialized cells, ensuring tissue repair and renewal. However, as time passes, the wellspring of these regenerative powerhouses gradually diminishes—a phenomenon known as the exhaustion of stem cells, a hallmark of aging.
Stem cells are instrumental in maintaining tissue health and vitality. They ensure that damaged or aged cells are replaced with fresh, functional ones, allowing tissues to retain their strength and functionality. However, with age, stem cells lose their potency. They become less able to divide and differentiate, leading to reduced tissue repair and a decline in overall regenerative capacity.
The consequences of stem cell exhaustion ripple across the body. Tissues that once enjoyed rapid renewal slow down, leading to weakened bones, thinning skin, and impaired healing. The decline in stem cell activity also affects the immune system's ability to respond effectively to challenges, making the body more susceptible to infections and diseases.
Strategies to combat stem cell exhaustion are a focus of intensive research. Some approaches involve enhancing the function of existing stem cells, while others explore the potential of stem cell transplantation to rejuvenate tissues. Additionally, understanding the signals that control stem cell behavior can lead to interventions that promote their activity and extend their regenerative potential.
Just as a well-maintained spring provides a constant source of rejuvenating water, robust stem cells supply the body with a continual stream of renewal. By delving into the mechanisms behind stem cell exhaustion, researchers aim to tap into the potential of these cellular architects, seeking ways to rejuvenate aging tissues and restore the body's ability to regenerate and thrive.
10. Altered Intercellular Communication: Disrupted Conversations
In the intricate world of our bodies, communication between cells is akin to a network of messengers delivering vital information. Just as a harmonious orchestra relies on precise cues from the conductor, our cells depend on accurate signals to orchestrate various bodily functions. However, as the years pass, the lines of communication can become muddled, giving rise to a hallmark of aging: altered intercellular communication.
Cellular communication is essential for coordinating processes such as growth, repair, and immune responses. Think of these messages as emails sent between colleagues in a busy workplace. In youthful bodies, these messages are sent and received seamlessly, ensuring that every part of the system works in harmony. However, as we age, the transmission of signals can become distorted or delayed, leading to misinterpretations and disruptions in cellular activities.
The repercussions of altered intercellular communication are significant. Much like a miscommunication in a team leading to errors and inefficiencies, cells can become dysfunctional or contribute to age-related diseases when communication falters. This breakdown in signaling can also impact the body's ability to respond to stressors, leaving it vulnerable to infections and other challenges.
One concrete example is the way immune cells communicate during an immune response. In aging, this communication can falter, resulting in a compromised ability to fight off infections and contributing to chronic inflammation—a hallmark of many age-related diseases.
Scientists are delving into ways to restore effective intercellular communication. It's similar to improving the reliability of a global communication network. Researchers are investigating signaling molecules and pathways to find ways to optimize their function. Lifestyle factors, such as maintaining a healthy diet and regular exercise, can also contribute to enhancing intercellular communication.
In summary, the language of intercellular communication guides the symphony of life within us. By studying and addressing the disruptions in this language, researchers are working toward promoting healthier aging. Just as clear communication is key to successful teamwork, restoring accurate cellular conversations could lead to improved well-being and a more graceful journey through the later stages of life.
11. Chronic Inflammation: Inflammaging Takes Center Stage
As the chapters of our lives unfold, one recurring theme emerges—the role of chronic inflammation in the aging narrative. Often referred to as "inflammaging," chronic inflammation becomes a central character in the story of our bodily changes over time.
Imagine inflammation as a persistent background hum, like a low-grade fever that never quite subsides. Inflammation is a natural response that helps our bodies fight infections and repair damaged tissues. However, as the years go by, this response can sometimes become overactive and prolonged, resembling an actor who refuses to exit the stage after their lines have been spoken.
The effects of inflammaging are profound. Much like a smoldering fire weakens the foundation of a building, chronic inflammation can contribute to the gradual breakdown of our bodily systems. It's like a storm that leaves a trail of destruction in its wake, promoting the development of various age-related diseases, from heart conditions to neurodegenerative disorders. Moreover, it accelerates the overall aging process, as the body struggles to repair the damage caused by persistent inflammation.
Researchers are working to understand the complexities of chronic inflammation. They're like detectives unraveling a complex plot, seeking ways to control and manage this overactive immune response. Lifestyle choices, including a balanced diet, regular exercise, and stress reduction, can help keep chronic inflammation in check.
In the grand narrative of aging, inflammaging is a central theme. But just as a skilled writer can reshape a story's direction, researchers are exploring ways to rewrite the aging script. By addressing chronic inflammation, they hope to create a more vibrant and fulfilling later chapter of life—a time of vitality and well-being that extends well into the golden years.
12. Dysbiosis: Gut Health and Aging
Within our bodies resides a bustling community of microorganisms, collectively known as the gut microbiota. These microbial residents play a crucial role in various bodily functions, from digestion to immune system regulation. However, as the clock continues to tick, the delicate balance within this microbial ecosystem can become disrupted—a phenomenon known as dysbiosis. This imbalance is a hallmark of aging that holds profound implications for our overall well-being.
Think of the gut microbiota as a diverse and harmonious orchestra, with each microorganism playing a specific instrument. In youth, this orchestra produces harmonious melodies that support digestion and health. However, with advancing age and various factors such as diet, medications, and lifestyle changes, the composition of this orchestra can become dissonant. Some microorganisms flourish while others dwindle, disrupting the intricate symphony of the gut.
The consequences of dysbiosis are far-reaching. Just as a disrupted ecosystem can lead to imbalances in a natural environment, an imbalanced gut microbiota can impact digestion, metabolism, and even immune responses. This imbalance has been linked to a range of age-related conditions, from gastrointestinal issues to chronic inflammation and neurodegenerative diseases.
Researchers are delving into the complex world of the gut microbiota. It's like exploring a vast and uncharted landscape, seeking to understand the interactions between different microorganisms and their impact on health. Strategies to address dysbiosis include dietary interventions, probiotics, and prebiotics—substances that support the growth of beneficial microorganisms.
Gut health is a crucial component of healthy aging. By nurturing a balanced gut microbiota, researchers aim to promote overall well-being and extend the years of vitality. Just as a harmonious orchestra produces beautiful music, a balanced gut microbiota supports optimal bodily function, enabling us to age gracefully and enjoy a higher quality of life.
Here are some research papers.
Genomic Instability:
Vijg, J. (2014). Aging of the Genome: The Dual Role of DNA in Life and Death. Oxford University Press.
Hoeijmakers, J. H. (2009). DNA damage, aging, and cancer. New England Journal of Medicine, 361(15), 1475-1485.
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
Telomere Attrition:
Blackburn, E. H. (2005). Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS letters, 579(4), 859-862.
Blasco, M. A. (2007). The epigenetic regulation of mammalian telomeres. Nature Reviews Genetics, 8(4), 299-309.
Epigenetic Alterations:
Fraga, M. F., Esteller, M., & González-Suárez, E. (2007). Epigenetics and aging: the targets and the marks. Trends in Genetics, 23(8), 413-418.
Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome Biology, 14(10), R115.
Loss of Proteostasis:
Koga, H., Kaushik, S., & Cuervo, A. M. (2011). Protein homeostasis and aging: The importance of exquisite quality control. Ageing Research Reviews, 10(2), 205-215.
Balch, W. E., Morimoto, R. I., Dillin, A., & Kelly, J. W. (2008). Adapting proteostasis for disease intervention. Science, 319(5865), 916-919.
Impaired Macroautophagy:
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011). Autophagy and aging. Cell, 146(5), 682-695.
Madeo, F., Tavernarakis, N., & Kroemer, G. (2010). Can autophagy promote longevity?. Nature Cell Biology, 12(9), 842-846.
Dysregulated Nutrient-Sensing:
Kennedy, B. K., & Lamming, D. W. (2016). The mechanistic target of rapamycin: the grand conductor of metabolism and aging. Cell Metabolism, 23(6), 990-1003.
Fontana, L., & Partridge, L. (2015). Promoting health and longevity through diet: from model organisms to humans. Cell, 161(1), 106-118.
Mitochondrial Dysfunction:
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
Wallace, D. C. (2010). Mitochondrial DNA mutations in disease and aging. Environmental and Molecular Mutagenesis, 51(5), 440-450.
Cellular Senescence:
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015). Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nature Medicine, 21(12), 1424-1435.
Exhaustion of Stem Cells:
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
Rando, T. A., & Chang, H. Y. (2012). Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell, 148(1-2), 46-57.
Altered Intercellular Communication:
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
Franceschi, C., & Campisi, J. (2014). Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69(Suppl_1), S4-S9.
Chronic Inflammation:
Franceschi, C., & Campisi, J. (2014). Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69(Suppl_1), S4-S9.
Fabbri, E., An, Y., Zoli, M., & Simonsick, E. M. (2018). Bioinformatics in Aging Research. In "Aging Research - Methodological Issues" (pp. 195-213). Academic Press.
Dysbiosis:
Claesson, M. J., Jeffery, I. B., Conde, S., Power, S. E., O'Connor, E. M., Cusack, S., ... & O'Toole, P. W. (2012). Gut microbiota composition correlates with diet and health in the elderly. Nature, 488(7410), 178-184.
Biagi, E., Candela, M., Fairweather-Tait, S., & Franceschi, C. (2012). Aging of the human metaorganism: the microbial counterpart. Age, 34(1), 247-267.