Hallmarks of Aging are a set of interconnected cellular and molecular processes or mechanisms that contribute to the aging process. They were first proposed in 2013 by researchers Carlos López-Otín, Maria A. Blasco, Linda Partridge, Manuel Serrano and Guido Kroem, who identified a pattern of markers in age-related diseases.
The field of research into ageing markers is constantly evolving. To better understand the causes of canine ageing, let's take a look at each of the ageing markers proposed so far and their implications for pet health.
Epigenetic changes
Epigenetic alterations are changes that regulate the activation of genes without altering the DNA sequence.
These changes act like switches, turning genes on or off.
Over time, these regulations can be affected, leading to the activation of harmful genes and the switching off of protective genes.
This disrupts the structure of our DNA and can contribute to ageing and health problems such as cancer.
Loss of proteostasis
Over time, our cells struggle to maintain and process proteins properly. As we age, there is an accumulation of proteins that don't fold or function as they should.
This can interfere with proper cell function and even trigger diseases associated with old age. Proteins are fundamental to the activities of our cells, and any failure in this maintenance system can have consequences for our health.
Mitochondrial dysfunction
Have you ever heard the song "Mitochondria, mitochondria do the breathing?" Well, just as the lung is essential to us, so are mitochondria to the cell. Mitochondria act as energy generators for our cells.
As we get older, these "generators" start to suffer damage, resulting in less energy for the cells. This decline in mitochondrial efficiency not only leads to a decrease in cellular energy, but also contributes to other problems associated with ageing.
Therefore, without healthy and efficient mitochondria, our cells are unable to function at their full potential, accelerating the signs and symptoms of ageing.
Wear or shortening of telomeres
Telomeres, which are protective structures located at the ends of chromosomes, become shorter and deteriorate over time, which affects the stability of chromosomes.
Each time a cell divides, the telomeres get a little shorter. Eventually, when they become too short, cells cannot divide effectively, leading to cell failure and ageing.
This shortening of telomeres is closely linked to the aging process and the limited capacity of cells to regenerate over time.
Cellular senescence
As we get older, our body begins to accumulate senescent cells, also known as "zombie cells".
It is normal for healthy cells to suffer damage over time and instead of going through the natural process of cell death. The zombie cells persist and release harmful substances that can affect neighboring healthy cells.
For example, the accumulation of these cells in the skin can result in wrinkles. In blood vessels, they can make them stiffer, increasing the risk of atherosclerosis. In the brain, they can contribute to inflammation and signs of ageing.
Genomic Instability
Another main characteristic of cellular aging is genomic instability. This process reproduces failures in DNA replication when it divides, resulting in frequent mutations and damage to the cells' genetic material.
For example, a new mole on your skin is nothing more than a damaged cell that is replicating itself.
Normally, our body is efficient at repairing these small alterations. However, with time and ageing, the ability to repair this damage decreases, leading to genomic instability.
And it is precisely this instability that can lead to mutations which, in some cases, can promote the development of age-related diseases such as cancer.
Stem Cell Exhaustion
Stem cells are like our body's rechargers, capable of transforming into various types of cells and helping to renew and repair tissues. Over time, as we get older, the quantity and effectiveness of these stem cells decreases.
This means that our ability to regenerate and heal tissues is reduced over time, accelerating the ageing process.
This decline is also a contributing factor to many age-related diseases, as the replacement of healthy cells becomes less efficient.
Deterioration of Cellular Communication
Communication between cells is like a telephone network that keeps our bodies working in harmony. However, as we get older, this network begins to fail.
Cells can start sending the wrong signals or not receiving messages correctly, impairing the body's balance and functioning.
This "noise" in communication can lead to problems such as insulin resistance, inflammation and other imbalances that accelerate ageing. The research seeks to better understand these flaws in order to create ways to optimize cellular communication as we age.
Other proposed causes of ageing
In 2022, experts from around the world came together to fill in the gaps left by a study carried out almost a decade earlier, in 2013, by López-Otin. Their renewed findings were featured in the renowned scientific journal Aging.
As a result, there are other new proposals for the causes or characteristics of ageing. These are:
Autophagy
Previously, it was believed that autophagy, a mechanism where cells "clean up" defective components, was linked only to proteostasis.
However, new analyses suggest a distinction: while proteostasis focuses on protein maintenance, autophagy acts on organelle recycling.
Both are fundamental, but play different roles in the context of ageing.
Splicing Dysregulation: Understanding RNA
Unlike genomic instability, which focuses on DNA, and epigenetic alterations, which analyze DNA methylation, splicing is an RNA construction mechanism.
In older individuals, there is a failure in this process, highlighting the importance of investigating this deregulation.
Microbiome
The composition of the gut microbiome changes as we get older.
But which came first: aging or changes in the microbiome? This is a relationship that deserves special attention.
Mechanical properties
Changes both inside and outside the cells have been brought to light. Internally, the dysfunction of the lamina, which is crucial for protecting DNA, stands out.
In the extracellular environment, collagen cross-linking is observed, which directly affects tissue elasticity and, consequently, cell mobility.
Inflammation
Chronic inflammation, or "inflammaging", has been linked to ageing for some time. However, its complexity and impact on the body suggest that it deserves to be studied as an individual milestone, distinct from communication between cells.
These discoveries are the beginning of a new era of understanding about aging and have the potential to shape future research and treatments related to longevity.
Are Hallmarks universal?
It's important to remember that although the Hallmarks are the main guides to ageing, they were identified on the basis of studies carried out on human beings and animal models, such as mice.
Most mammals show similar biological aging processes, although the rate and specific details can vary between species. Therefore, many of the hallmarks of ageing probably apply, to a greater or lesser extent, to mammals other than humans.
But a recent review, from 2023, "A revisiting of "the hallmarks of aging" in domestic dogs: current status of the literature" by researcher" Ana Gabriela Jiménez,
stated that there are gaps in the literature comparing other mammals and dogs and highlighted aging markers that may be missing for dogs as aging study models.
The author also advocates the importance of studies on aging in dogs addressing various breeds and different ages. In addition, she suggested the need to make age corrections for breeds with different average life expectancies.
References:
Lifespan Brazil. Markers of Ageing. Available at: https://lifespan.com.br/2023/03/29/marcadores-envelhecimento/.
López-Otín, Carlos et al. "The hallmarks of aging." Cell vol. 153,6 (2013): 1194-217. doi:10.1016/j.cell.2013.05.039
Schmauck-Medina, Tomas et al. "New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary." Aging vol. 14,16 (2022): 6829-6839. doi:10.18632/aging.204248
Jiménez, A. G. (2023). A revisiting of "the hallmarks of aging" in domestic dogs: current status of the literature. Journals of Gerontology. https://doi.org/10.1007/s11357-023-00911-5