There are few experiences in this world as universal as aging. While everyone may interface with ‘ol Father Time at different rates, the end result is always the same. Considering how ubiquitous the process of aging is, most people are not taught the biological correlates of aging. In our episode with David Sinclair, we briefly touched upon many of the bodily changes that are thought to cause our bodys’ slow decay. I’d like to take a moment to go into a little more detail on each of the processes we mentioned!
Genomic Instability: This refers to the collection of mutations (DNA alterations) that accumulate within our own personal genome (genetic code). Every time our cells replicate there are opportunities for mistakes to be made during the replication process. Most of these mistakes are harmless, however, over time we can accumulate enough mutations that we develop abnormalities. Additionally, exposure to environmental mutagens, such as carcinogenic chemicals and UV radiation, lead to additional mutations. This is why your likelihood of developing cancer dramatically increases as you age. Your body has more opportunities to make mistakes (Aguilera & Gómez-González, 2008; Fakouri et al., 2018; Vjig & Montagna, 2017).
Degradation of telomeres: At the ends of each chromosome there are special sequences to DNA called telomeres. These sequences are designed to bond to each other as well as other parts of the chromosomes to essentially tie knots at the ends of each strand. This prevents the DNA from fusing together (which can cause DNA damage and add to genomic instability). Due to an idiosyncrasy in the way our DNA replicates, each time our genome is replicated, the telomeric “caps'' at the end of the DNA get shorter and shorter, until they eventually become used up. At this point, each replication will result in loss of actually important genetic information (Shammas, 2011; Vaiserman & Krasnienkov, 2021).
Alterations to the epigenome: Our DNA is very long and has genetic code that helps the body make proteins to tackle any situation thrown at it. If we had to replicate the whole genome each time we wanted a new protein, DNA transcription would take too long. Our cells get around this through epigenetics (modifications to genetic code). Epigenetic modifications cause sections of DNA to loosen or coil. The coiling of DNA essentially makes it unable to be read (so that we don’t transcribe it into RNA and later, proteins). The loose parts are easily read and used to produce the desired product. Environmental experiences, such as stress and illness, cause epigenetic modifications of the DNA. Over time, these alterations can lead to genome instability (Gonzalo, 2010; Zhang et al., 2020)
Mitochondrial dysfunction: Many of you may remember the mitochondria as “The powerhouse of the cell.” In reality, the mitochondria does much more than simply generate energy. It also sends signals to the cell as to when to undergo apoptosis (essentially cell suicide if there is irreperable damage to the cell). Another important piece to note about the mitochondria is that it has its own DNA that is separate from your genome. This mitochondrial DNA (mDNA) is less stable than your normal DNA accumulates mutations at a more rapid rate. Improperly functioning mitochondria can cause cells to die early, cells to live even though they should be replaced, and electrons to leak out of the energy making process where they can cause damage and inflammation (Cui et al., 2012; Haas, 2019; Paterson, 2014).
Exhaustion of stem cells: Stem cells are a special category of cells that can differentiate into other cell types. The balance of stem cell differentiation helps in bodily regeneration and the maintenance of healthy organ systems. Like all other cells, the additional time that comes with age allows for the accumulation of mutations that can alter function. For stem cells, this can cause abnormal accumulations of cells (which can lead to cancerous tumors) as well as a reduced capacity to heal from bodily injuries and regenerate cells (Oh et al., 2014; Ruzankina & Brown, 2007).
Alteration of cellular communication: The increasing levels of inflammation seen in aging, coupled with the changes in our cellular and bodily environments due to genomic instability, cause decreased efficiency in our neuronal and hormonal signaling pathways. This can affect various aspects of metabolic function including our blood clotting system, insulin sensitivity, and cell growth (López-Otín et al., 2013; Mays Hoops, 2010).
Production of Inflammatory molecules: Dysfunctions of the mitochondria, as well as genomic instability, and altered cellular communication, can cause dysfunction of our immune system and chronic levels of inflammation. This puts stress on bodily systems, leading to negative metabolic changes (such as obesity and Type II diabetes, atherosclerosis, and much more), which further degrade our health (López-Otín et al., 2013; Sanada et al., 2018).
While this extensive list may seem daunting, it provides us with the blueprints necessary to slow the aging process. By engaging in healthy behaviors, maintaining a good diet, practicing stress reduction, avoiding contact with mutagens, and regular exercise can all help in both preventing and repairing damage (Parker-Pope, 2021; Penn Medicine, 2019).