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Yazarın fotoğrafıMetin Sokmen, MD

Pathological Mechanisms of Kidney Disease in Ageing

Hallmarks of kidney ageing


Genomic Instability, Telomere Shortening, and Epigenetic Alterations

These are classified as 'primary' hallmarks that accumulate over time and definitively contribute to the aging process.


Cellular Senescence

This is the irreversible halt of the cell cycle in response to DNA damage and telomere attrition, categorized as an 'antagonistic' hallmark reflecting damaging responses during aging.



Mitochondrial Dysfunction and Oxidative Stress

These hallmarks are characterized by a decrease in energy production and an increase in the production of free radicals, which can contribute to age-related damage in the kidneys.


Disruptions in Lipid Metabolism

Disruptions in lipid metabolism occur with age and can contribute to the progression of kidney diseases.


Klotho, Phosphate Toxicity, and Calciprotein Particles

Deficiency in Klotho can lead to premature aging and a shortened lifespan.



Autophagy Impairment

A decrease in autophagy capacity with age can lead to improper degradation of cellular components, contributing to cellular aging.


Lysosomal Dysfunction

Lysosomes can become impaired during the aging process, affecting autophagy and contributing to cellular aging.


 

CKD is associated with accelerated or premature ageing to the extent that the biological age of patients with CKD is approximately 5 years older than their chronological age.


Moreover, and as mentioned previously, CKD is an important risk factor for the progressive ageing of other organ systems such as the brain and heart.


The higher biological age of the kidney in patients with CKD relative to chronological age may be mediated by pathophysiological mechanisms that are common to both ageing pathways and CKD.



These effects culminate in a high risk of cardiovascular events and sarcopenia, contributing to impaired health status, reduced quality of life and premature mortality in individuals with CKD.




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