Understanding the Connection Between Aging and Disease
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Chapter 1: The Complexity of Aging
Aging presents challenges, both personally and in the context of research. It impacts every tissue in our bodies, making it difficult to pinpoint a single molecule or pathway responsible for the aging process. Rather, aging is a complex biological event resulting from numerous interacting mechanisms.
To bring some clarity to this complexity, researchers have identified nine hallmarks of aging:
- Genomic instability
- Telomere attrition
- Epigenetic changes
- Loss of proteostasis
- Deregulated nutrient-sensing
- Mitochondrial dysfunction
- Cellular senescence
- Stem cell depletion
- Altered intercellular communication
Additionally, there are seven pillars that highlight critical research areas within geroscience:
- Metabolism
- Macromolecular damage
- Epigenetics
- Inflammation
- Stress adaptation
- Proteostasis
- Stem cells and regeneration
While these hallmarks and pillars have significantly influenced aging research, two prominent figures in the field argue that it's time to evolve beyond these frameworks. They suggest that while these concepts have shaped research, they have also masked the pressing need to create a concrete paradigm to better understand the mechanistic causes of various aging-related diseases.
As we delve into the topic of aging pathologies, it is well-known that aging, or more specifically senescence, often coincides with disease. In many cases, multiple age-related diseases manifest together, a phenomenon referred to as multimorbidity.
Section 1.1: Disease Clusters and Biological Mechanisms
Recent research has sought to unravel some of the biological mechanisms underlying age-related diseases, thereby identifying which diseases are likely to co-occur. By analyzing nearly one million literature abstracts and combining this data with clinical information from over three million individuals, researchers have discerned five key aging mechanisms that correlate with different clusters of age-related diseases.
The following are the five mechanisms along with ten commonly associated diseases:
- Deregulated nutrient sensing
- High cholesterol, elevated LDL, low HDL, hypertension, chronic kidney disease, coronary artery disease, high triglycerides, type 2 diabetes, fatty liver.
- Mitochondrial dysfunction
- Cardiomyopathy, lung cancer, congestive heart failure, chronic kidney disease, type 2 diabetes, sepsis, dementia, motor neuron disease, Parkinson’s disease.
- Cellular senescence
- Chronic obstructive pulmonary disease, lung cancer, colorectal cancer, breast cancer, melanoma, viral infections, immunodeficiency, cirrhosis, liver cancer, stomach cancer.
- Stem cell exhaustion
- Osteoarthritis, plasma cell cancer, anemia, hemolytic anemia, aplastic anemia, leukemia, myelodysplasia, polycythemia vera, coronary heart disease, myocardial infarction.
- Altered intercellular communication
- Syndrome of inappropriate antidiuretic hormone secretion, type 2 diabetes, chronic obstructive pulmonary disease, prostate cancer, chronic kidney disease, hyperparathyroidism, osteoporosis, thyroid disease, rheumatoid arthritis, breast cancer.
The researchers conclude that their findings support the role of aging hallmarks in the development of human age-related disease multimorbidities and diseases with incomplete pathogenesis. Future studies may explore whether targeted interventions can effectively prevent or treat these multimorbidities.
This video explores the relationship between aging and various diseases, providing insights into underlying biological mechanisms.
Section 1.2: Causation vs. Association
It’s important to note that while these diseases are correlated, this does not imply causation. Each disease has its own strong association with potential mechanisms. Although there is supporting evidence from mechanistic studies conducted in cell cultures, animal models, and occasionally human patients, causation cannot be definitively established solely from this research.
Furthermore, many of these diseases exhibit overlapping characteristics. For instance, high cholesterol includes both HDL and LDL components, and diabetes mellitus encompasses type 2 diabetes. Such overlaps are inherent in text mining, where classifications depend on the definitions used by the original study authors.
The key takeaway is clear: aging brings with it a host of challenges.
Chapter 2: Exploring Aging and Disease
This video takes a deeper look at aging, its effects on health, and the complexities of aging-related diseases.
In conclusion, thank you for engaging with this exploration of aging and its associated diseases. If you’re interested, consider subscribing to my newsletter, Thinking Ahead, where I delve into broader topics in science, philosophy, technology, and even fiction.
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