Over time, DNA accumulates damage from various sources like radiation, chemical exposure, and replication errors. Our DNA repair mechanisms become less efficient with age, leading to mutations and chromosomal abnormalities. This genomic instability can lead to cellular dysfunction, increased cancer risk, and accelerated aging.

Telomere attrition is the gradual shortening of these protective caps over time. This process occurs naturally as cells divide, but it's also influenced by factors like stress, poor diet, and environmental toxins. Think of it as the biological equivalent of a countdown timer – as telomeres shorten, cells age and eventually lose their ability to divide properly.

Epigenetic changes involve modifications to DNA or histones that affect gene expression without altering the DNA sequence. With age, there's a global decrease in DNA methylation, yet increased methylation at specific gene promoters. This leads to altered gene expression patterns, often silencing tumor suppressor genes or activating harmful genes, which can disrupt cellular function and contribute to age-related diseases.

Proteostasis is the balance between protein production, folding, and degradation. As we age, this balance is disrupted. Misfolded or damaged proteins accumulate, forming toxic aggregates that cells struggle to clear. This is seen in neurodegenerative diseases like Alzheimer's. Additionally, the efficiency of protein-degrading systems like the ubiquitin-proteasome system and autophagy declines, further compromising cellular health.

Autophagy is the process by which cells break down and recycle damaged components. It's crucial for maintaining cellular health, especially under stress. With age, autophagy becomes less efficient. This leads to the accumulation of damaged organelles, misfolded proteins, and other cellular "junk." Impaired autophagy is particularly problematic in non-dividing cells like neurons, contributing to neurodegenerative diseases. Interestingly, interventions that enhance autophagy, like fasting, show promise in extending healthspan.

Nutrient-sensing pathways like insulin/IGF-1, mTOR, and sirtuins play crucial roles in metabolism and longevity. With age, these pathways become less sensitive, leading to metabolic disorders. For example, insulin resistance can lead to type 2 diabetes. Conversely, reducing nutrient signaling through caloric restriction or drugs like rapamycin (mTOR inhibitor) can extend lifespan in various species.

Mitochondria are the cell's powerhouses, producing ATP through oxidative phosphorylation. However, this process also generates reactive oxygen species (ROS) that can damage mitochondrial DNA. Over time, this leads to less efficient energy production and more ROS, creating a vicious cycle. Mitochondrial dysfunction is linked to fatigue, muscle weakness, and neurodegenerative diseases in aging.

When cells experience stress or damage, they can enter a state of senescence—they stop dividing but remain metabolically active. Senescent cells secrete pro-inflammatory factors, chemokines, and growth factors (the senescence-associated secretory phenotype or SASP), which can damage surrounding tissues. While senescence prevents cancer by halting the division of damaged cells, the accumulation of senescent cells contributes to aging-related inflammation and tissue dysfunction.

Stem cells are crucial for tissue repair and regeneration. However, as we age, their number and function decline—a process called stem cell exhaustion. This is partly due to the accumulation of damage, epigenetic changes, and the effects of the aged tissue environment. Consequently, tissues lose their regenerative capacity, leading to slower wound healing, muscle loss, cognitive decline, and graying hair.

Cellular communication refers to the process of cells in the body exchanging information and signals with each other. Cells use various methods, such as releasing chemical messengers (hormones, neurotransmitters) or direct physical contact, to convey essential instructions for coordinating various functions and responses within the body.

Also known as "inflammaging," this hallmark involves a low-grade, chronic inflammatory state that develops with age. It's driven by factors like senescent cell accumulation, mitochondrial dysfunction, and changes in the gut microbiome. Unlike acute inflammation, which aids healing, chronic inflammation damages tissues over time. It's a key factor in age-related diseases like atherosclerosis, Alzheimer's, some cancers, various health issues, including autoimmune diseases, cardiovascular problems, and some neurodegenerative conditions.

Microbiome dysbiosis refers to an imbalance or disruption in the composition of the trillions of microbes that reside in our body, known as the microbiome. When the balance of these microbes is disturbed, certain harmful microorganisms may overgrow while beneficial ones decrease, leading to potential health problems.