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As We Age

​WHAT HAPPENS WHEN WE AGE? WE AGE?

Aging Aging

Aging occurs biologically as a result of the accumulation of numerous types of molecular and cellular damage over time. This causes a slow loss of physical and mental ability, a rise in the risk of disease, and finally death.

Some of the hallmarks of aging include:

  • Genomic instability
  • Telomere attrition
  • Epigenetic alterations
  • Loss of proteostasis
  • Deregulated nutrient-sensing
  • Mitochondrial dysfunction
  • Cellular senescence
  • Stem cell exhaustion
  • Altered intercellular communication

STEM CELL DETERIORATION

Stem cells have the capacity for multiple types of differentiation as well as self-renewal. Under typical physiological settings or in response to injury, they mediate tissue development and regeneration. There is increasing evidence that stem cells are affected by the aging process. As the body ages, the ability of stem cells to renew themselves and differentiate into specific cell types decreases.

 

Our stem cells in the body decrease as we age

Stem cells differentiation processes that occur in the human body

Understanding how aging affects stem cell function is crucial for the development of effective stem cell-based therapies to treat age-related diseases and for gaining insight into the underlying mechanisms of aging-associated disorders.

WHAT CAUSES STEM CELL DETERIORATION? CELL DETERIORATION?

Daughter cells inherit epigenetic markers from stem cells, which prime lineage-specific loci for change in subsequent offspring. Alterations in epigenetic regulation have an impact on stem cell aging, haematological cancer susceptibility, and organismal aging. Many aging-related disorders are likely caused in part by a number of potential processes that are thought to contribute to stem cell malfunction with aging. Below are some of the causes of stem cell degeneration:
 

1. Microenvironment 1. Microenvironment

asw-microenvironment
Hormonal, immunologic and metabolic problems are thought to be major microenvironmental factors influencing stem cell functioning. It is believed that changes in stem cell function in response to aging are caused by adjustments to these microenvironmental variables.

Endocrine or paracrine soluble factors produced by cells are required for communication between cells of the same organ or distant tissues. Hormonal abnormalities brought on by aging of the endocrine glands have been reported to interfere with stem cell differentiation or proper function.

2. Mitochondrial Dysfunction 2. Mitochondrial Dysfunction

asw-mitochondrial-dysfunction_orig
Age-related Reactive Oxygen Species (ROS) production, Ca²+ homeostasis problems, and an increase in cell apoptosis are three factors that contribute to mitochondrial dysfunction and age-related illnesses. It has been demonstrated that respiratory chain failure is caused by mitochondrial dysfunction, which may be the result of an accumulation of mitochondrial DNA mutations.

While the primary cause in still unknowns, mitochondrial DNA (mtDNA) mutation is speculated to be the reason behind the increased production of ROS associated with aging, as mitochondria are the primary biological producers of ROS. Additionally, it has been established that mitochondrial aging interacts with other cellular mechanisms of ageing, such as the mTOR and IGF-1 signaling pathways, which are thought to be important in aging.

3. Epigenetic Alteration 3. Epigenetic Alteration

asw-epigenetic-alteration_orig
​Epigenetics means the study of variations in gene expression that can be inherited without changing the DNA sequence. ​Epigenetic alterations to DNA that preserve the memories of active and silent gene states control stem cell fates.

​4. Telomere Shortening ​4. Telomere Shortening

asw-telomere-shortening_orig
A telomere is a section of nucleotide sequences that repeat at both ends of a chromosome. It guards the genome against unwanted recombination, repair, or fusion with nearby chromosomes as well as nucleolytic destruction.

Telomere shortening, which is widely recognized as a symptom of aging and to which even stem cells are susceptible, has attracted a lot of interest especially in age-related illnesses. In actuality, accelerated telomere shortening is the root cause of many aging-related disorders, including higher cancer risk, coronary heart disease, heart failure, diabetes, and osteoporosis. The cell changes when telomeres are critically shortened. Senescent cells stop dividing and may experience apoptosis. 
asw-dna-damage_orig
Every day, DNA experiences intrinsic and extrinsic mutational events. Majority of damaged DNAs are fixed by the regular DNA repair process however, certain mutant DNAs seem to be able to evade the repair process and build up over time.
 
Both external influences, such as UV irradiation, and cellular activities, such as the production of ROS that tend to build over time, can result in DNA damage. The numerous cellular ageing events could partly be attributed to the accumulation of damaged DNA.

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