What Are the Hallmarks of Aging?
Aging is a natural and time-dependent decline in body function due to alterations at the molecular and cellular levels that leads to changes in the function of the cardiovascular system, the brain, the digestive system, the bladder and urinary tract, the muscles, joints, and muscles, the eyes and ears, the teeth, and the skin. Changes in body weight and sexuality are also observed.
The molecular and cellular changes responsible for these physiological declines have been grouped under the name hallmarks of aging [1].
Hallmarks of Aging
1- Genomic instability
Our DNA integrity and stability are constantly confronted with external physical, chemical, and biological damaging factors, and internally through reactive oxygen species (ROS) and DNA replication errors. These damaging effects result in DNA mutations, chromosomal aberrations, and telomere shortening that lead to genomic instability responsible for diseases such as cancer [2].
However, during evolution, organisms developed DNA repair mechanisms that ensure genomic stability through the repair of DNA mutations and the maintenance of telomere length and appropriate chromosomal segregation. Unfortunately, these repair mechanisms are severely affected by age.
2- Stem Cell Exhaustion
Within tissues and organs of the body, populations of stem cell-like cells known as adult stem cells, or adult tissue-specific stem cells maintain and repair tissues and organs throughout the life of an individual.
However, as we age, these populations of cells start to deplete due to several causes that can act individually or collectively such as DNA damage, proteostasis, epigenetics, telomere shortening, mitochondria dysfunction, and cellular senescence [3].
3- Telomere Attrition
During aging, a shortening of telomeres-specialized chromatin structures that are found at the end of chromosomes leads to gene erosion and chromosomal aberrations that result in functional inactivation, death, or senescence of cells.
For instance, the loss-of-function of Shelterin, a protein complex that protects telomeres and promotes telomerase activity, has been shown to accelerate aging and decrease tissue regeneration [4].
4- Loss of Proteostasis
As products of DNA transcription and RNA translation, proteins are molecules that are involved in all functional activities within the cells. However, when proteins are generated, they must pass a quality control test that relies on checking their synthesis, folding, and degradation. This process is known as protein homeostasis or proteostasis.
Unfortunately, this process is also affected with age leading to abnormal folding, toxic aggregation, and accumulation of damaged proteins, that result in cellular damage and tissue dysfunction [5].
5- Alteration in Mitochondria Function
A theory proposed that elevated ROS are associated with a decline in the integrity of mitochondria [6]. Reactive oxygen species (ROS) that are produced by the mitochondria can induce oxidative damage to the mitochondria resulting in increased aging [7].
Accelerated aging was also proposed to be associated with a reduction of mitochondria energy flow, known as bioenergetics, due to a decline in the renewal of mitochondrial number and size (Biogenesis) with age [8].
6- Cellular Senescence
Cellular senescence is associated with cells that stopped dividing without entering a programmed cell death. This cellular arrest in growth is associated with non-telomeric DNA damage and shortening of the telomeres in senescent cells.
The role of senescent cells in aging is linked with their “senescence-associated secretory phenotype” characterized by the secretion of pro-inflammatory cytokines and matrix metalloproteinases that promote aging [9].
7-Epigenetic Alterations
During the process of aging, DNA is subject to epigenetic changes such as acetylation, methylation, post-translational modifications of histones, and chromatin remodeling. These changes control the expression of longevity genes. For instance, progeroid cells (faster-aging cells) exhibit DNA methylation patterns and histone modifications that mostly recapitulate those found in normal aging [10].
8- Alterations in Nutrients’ sensing
Nutrient sensing is the cell’s capacity to detect the levels of nutrients such as glucose and metabolites. The insulin and IGF-1 signaling pathways, growth hormone (GH), and the AMP-activated kinase (AMPK) are major nutrient-sensing pathways.
Interestingly, several studies showed a correlation between longevity and the reduction in growth hormone (GH) and in the IGF-1 signaling pathway [11] [12]. Through the activation of several metabolic pathways, AMPK has also been proposed to promote healthy aging [13].
9- Inflammation
Several studies have identified a link between chronic inflammation and longevity [14]. Although inflammation, such as acute inflammation is an essential event in immune response and tissue homeostasis, chronic inflammation has been associated with chronic diseases, including diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer.
These diseases are the main causes of bad quality of life, and death, and therefore, significantly reduce individuals’ lifespan. A group of genes named Conserved Transcriptional Response to Adversity (CTRA) appears to play a key role in linking chronic inflammation and longevity [15].
Conclusion
Although aging is a complex natural phenomenon that involves molecular, metabolic, and cellular alterations of tissues and organs, it is still possible to slow it down through healthy diets such as epigenetic and restrictive diets, and physical activity through frequent walks and exercise.
References
[12] Kenyon, C.J., 2010. The genetics of ageing. Nature, 464(7288), pp.504-512.
