**Abstract**

Kidney is one of the tissues affected by age that involves cellular and structural changes inside the kidney and notably implicates with comorbidity, related to cardiovascular disease aging. Aging kidney causes the elderly susceptible to clinical deterioration from ordinary stimulation that younger individual can compensate, including acute renal injury, volume depletion or overload, sodium and potassium level disorders, and toxic reaction against kidney excreted drugs. As one of the organs with the fastest aging rate, kidney shows several age-related decline in both structural and functional with 30% of the glomerulus are damaged and represent diffuse glomerular sclerosis by age 75 and explain why the prevalence of chronic kidney disease (CKD) and end-stage renal disease are very common in the elderly. The cross-sectional population-based study by The National Health and Nutrition Examination Survey supports the theory of age-related decline in kidney function, although some other subjects did not have an absolute decline in kidney function. The underlying molecular mechanisms could be the target of future therapeutic strategies. Aging is a natural biological process characterized by a gradual decline in cellular function as well as progressive structural change of organ systems. In aging kidney, there are interactions of genetic factors, environmental changes, and cellular dysfunction that lead to the typical structural and functional changes. One of the most popular theory of aging is the theory of free radicals or oxidative stress based on the fact that cells are under chronic oxidative stress due to an imbalance between pro oxidants and antioxidants. Reactive oxygen species are oxygen-derived oxidizing compounds that are highly reactive, consisting of free radicals and non-radicals. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) refer to both reactive radicals and non-radical derivatives of oxygen and nitrogen. Reactive oxygen and nitrogen species (RONS) are produced by all aerobic cells and play an important role in aging as well as age-related diseases. Lipid peroxidation is a process of oxidative degradation of lipids that process by which free radicals bind to lipid electrons in the cell membrane resulting in direct cell damage. Lipid peroxidation can cause cellular damage in several ways such as impairing the integrity of the plasma membrane and subcellular organelles by peroxidation, "chain reaction" of ROS production, and activation of phospholipase A2 (PLA2) caused by lipid peroxidation. Fatty acids and other PLA2 metabolites (such as lysophospholipids) are known to damage cell membranes. In the development of kidney damage, the process of lipid peroxidation plays an important role. This is presumably due to the large number of long-chain polyunsaturated fatty acids (PUFAs) in the lipid composition of the kidneys and there are substantial evidence to suggest that ROS is involved in the ischemic, toxic, and immunologically mediated pathogenesis of renal injury, but the cellular mechanisms that result in cell injury and death are still being studied.

**Keywords:** oxidative stress, aging, kidney

## **1. Introduction**

Kidney is one of the tissues affected by age. Aging involves cellular and structural changes inside the kidney and notably implicates with comorbidity, related to cardiovascular disease aging [1, 2]. The Centers for Disease Control and Prevention estimated that 72 million people in the United States (20% of population) will be 65 years old or more at 2030. Eurostat estimated, around 28% Europeans will be 65 years old at 2060. The increasing number of older adults will be predicted to increase aging related kidney disorders as well [3].

Aging kidney causes the elderly susceptible to clinical deterioration from ordinary stimulation that younger individual can compensate, including acute renal injury, volume depletion or overload, sodium and potassium level disorders, and toxic reaction against kidney excreted drugs [4]. Deficiency of kidney function is associated with death in all populations [2]. Several studies have shown that the decrease of function related to be structural (glomerulosclerosis, tubular atrophy and interstitial fibrosis) and functional (reduced glomerular filtration rate, proteinuria, decreased ability to concentrate or dilute urine, electrolyte imbalance and ion transport disorders, changes in hormonal function, reduced drug excretion) [1, 5].

As one of the organs with the fastest aging rate, kidney shows several agerelated decline in both structural and functional. The renal parenchyma decreases about 1%, and creatinine clearance or GFR decrease is about 1.0 mL/minute per 1.73 m2 per year in elderly subjects [6]. In normal aging kidneys, 30% of the glomerulus are damaged and represent diffuse glomerular sclerosis by age 75. Meanwhile the remaining glomerulus denote impaired filtration ability [2]. This could explain why the prevalence of chronic kidney disease (CKD) and end-stage renal disease are very common in the elderly [6]. Chronic kidney disease is a major growing health and economic burden. About 8–13% of the world's population suffers from CKD [7].

#### **2. Age-related kidney changes**

Age-related loss of kidney function has been recognized for decades. The cross-sectional population-based study by The National Health and Nutrition Examination Survey supports the theory of age-related decline in kidney function, although some other subjects did not have an absolute decline in kidney function. Although the rate of this decline is low, the process may have negative effects on many organ systems and thus reduce overall health and physical function in the elderly individual [6]. Epidemiological, clinical, and molecular evidence suggest that aging is a major contributor to the increased incidence of acute kidney injury and CKD. Renal function recovery after an episode of acute kidney injury is significantly worse in elderly patients. Reduction of regenerative potential, which is a feature of the aging process, may be caused by aging cells [8].

With increasing age, many individuals show progressive reductions in glomerular filtration rate (GFR), renal blood flow (RBF), and loss of nephron function with wide variability between individuals [9]. The aging kidney undergoes complex changes that affect the pathology of the kidney. The underlying molecular mechanisms could be the target of future therapeutic strategies [8].

The accumulation of old cells explains the ineffectiveness of cell repair and the loss of functional ability wherein studies have shown that the removal of old cells results in delayed kidney aging. Other potential mechanisms are autophagic changes responding to renal stress and the inflammatory response [8].
