“Senescence is the gradual deterioration of functional characteristics with age.”
Table of Contents
What is Senescence?
Senescence is a process in which cells reach permanent growth arrest without the death of cells as the whole cell division process comes to a halt.
It can either occur at the cellular level or senescence of the whole organism can take place.
It is characterized by a gradual functional decline eventuating heterogeneously across organ systems, leading to a progressive deterioration and ultimately leading to dysfunctioning of tissues.
This cellular program induces stable growth arrest.
The ageing process, on the whole, can be classified into three groups:
Causes of age-associated damage – Primary
Response to damage – Antagonist
Consequences of Responses – Integrative
As cells age, they enter into a state of senescence. They do not support the tissues or divide, instead, generate chemicals which have the potential to encourage nearby cells to enter into senescence.
They pose a threat as they can cause cancers, damage tissues and degrade their functionality, increase chronic inflammation etc.
Senescent cells destroy themselves through a process called apoptosis causing them to get eliminated by the immune system. With age, however, our immune system weakens and is unable to eliminate all these senescent cells which get accumulated over a period of time. Hence senescent cells are key in the progression of ageing as they cause inflammation and destroy surrounding body tissues.
Senescent cells secrete proinflammatory chemokines, cytokines and matrix proteases resulting in the formation of SASP (Senescence-associated secretory phenotype). SASP is known to contribute to cancer and the ageing process, and hence, the use of senolytics is the proposed method to combat senescence. Senolytics are a class of drugs which focus on the destruction of the senescent cells which are seemingly resistant to death.
Eliminating even 30% of senescent cells has been known to slow down the rate at which ageing occurs. Clearing senescent cells improve chronic hypercholesterolemia and various vascular ageing aspects.
Senolytics have also reduced mortality from cardiovascular diseases, and it is used for the treatment of Atherosclerosis, Diabetes type-2 and Osteoarthritis.
Also Read: DNA Replication – Machinery And Enzymes
Causes Of Senescence
Senescence or cell ageing occurs in different types of cells, namely: Melanocytes, Endothelial cells, epithelial cells, glial cells (nerve tissue), stem cells, adrenocortical cells, and lymphocytes. Listed below are a few causes.
One of the major causes of cell ageing is telomere erosion. We see a set of sequences towards the end of each chromosome, they are the telomeres. It consists of DNA of nucleotides which are repeated, they prevent chromosomes from losing information crucial for replication. It also prevents fusion with the surrounding chromosomes.
Telomeres lose small parts of DNA after each replication since enzymes which administer the process of duplication fail to reach the end of the chromosome. Hence, chromosomes lose principal genetic information after losing the telomere due to shortening, post every replication. This is the point where cells can no longer divide as they enter a DDR (DNA Damage Response) state. This is the stage of senescence.
As ageing is a natural process, the tendency of cells to enter the senescence state is natural and certain.
DNA Damage Of Various Kinds
Cellular senescence can be induced by damage to DNA by many other means, most commonly, DNA double-strand breaks. It causes cells to enter a DNA damage response state ultimately leading to cells turning senescent.
Cells can enter the DDR state through the presence of mitogenic signals, errors in proteins which promote cell proliferation and reactive oxygen species.
Few other factors are known to cause senescence such as Oncogene activation, irradiation, cell culture, and stress on mitochondrial homeostasis. Excessive mitochondrial ROS has known to initiate cell ageing.
The imbalance of mitochondrial homeostasis includes damaged mitochondrial dynamics, defects in chain transport of electrons, uncontrolled ROS synthesis, increased protein Kinase activity, decreased altered metabolism and accumulation of mitochondrial calcium.
Related Reading: Apoptosis
Effects Of Senescence
Senescence affects tumour growth which can be attributed to the age factor, where it is known to induce tumours in older entities, in younger entities, senescence helps combat tumours.
Another effect is the repair of tissues as senescence secretes molecules of different types some of which govern growth, healing of wounds, and signalling of foreign bodies to the immune system for their elimination. Hence, senescent cells are pivotal in tissue repair and also in producing signalling chemicals to detect and repair damaged tissues. Isolated senescent cells lack signalling capabilities to disarm surrounding immune cells.
Senescent cells arise from multiple mechanisms and cause a reduction in the functional capabilities of aged tissues. This provides a great scope for affected tissues to get deteriorated, further making them more susceptible to stressful events in the future.
Senescence in Plants
Like all other living organisms, plants have a specific life span during which they develop, grow and finally die. Before death, certain deteriorative processes occur in them, which terminate their functional life. These processes are known as senescence. The death of the plant or plant parts as a consequence of senescence is known as Programmed Cell Death.
Senescence is not confined to the entire plant, but to particular plant organs such as leaves or flowers. There are four types of senescence patterns in the plant:
This type of senescence occurs in the annual plants where the entire plant is affected and dies.
This type of senescence occurs in perennials and is seen only in the parts of the plant above the ground.
This takes place in the woody plants and is less drastic. It affects all the leaves of the plants.
This is the gradual progression of senescence of leaves from the base upwards as the plant grows.
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