Healthy Aging And The Kidneys: Lessons From Centenarians

Centenarians are a recognized model for healthy longevity and, despite age-related declines in kidney function, generally have a lower risk of cardiovascular disease. Understanding the molecular and cellular basis of healthy kidney aging in centenarians may provide clues to preventing or reducing the burden of kidney disease in older adults.

Click to Cistanche for kidney disease

Aging is associated with glomerular, interstitial, and vascular changes in the kidney, which in some individuals ultimately manifests as a decrease in glomerular filtration rate (GFR) and the development of chronic kidney disease (CKD). Aging is also complicated by the increased prevalence of obesity, diabetes, hypertension, and dyslipidemia, which further increases the risk of CKD. This suggests that precise examination of renal alterations in apparently healthy older adults may provide a valuable opportunity to elucidate the biology of intrinsic renal aging and potentially identify mechanisms that reduce or exacerbate CKD risk. ­

Centenarians are characterized by low cardiometabolic risk factors, including diabetes and dyslipidemia

Centenarians (100 years and older) are a group of extremely long-lived individuals characterized by significant resistance to risk factors commonly associated with morbidity. Therefore, centenarians are identified as models of healthy aging. Different methods have been used to decipher the biology and genetics of centenarians to identify key longevity pathways in humans. From an epidemiological perspective, centenarians have lower cardiometabolic risk factors, including diabetes and dyslipidemia. Instead, they were reported to have a higher frequency of CKD, with an estimated GFR (eGFR) of 60 ml/min per 1.73 m2 (Figure 1). A large part of this perceived increase in prevalence may be driven by the GFR threshold used to diagnose CKD, which is not adjusted for age. This approach has been challenged due to the impact of low muscle mass or sarcopenia on eGFR formulation. Research shows that current eGFR thresholds classify a large number of centenarians as having CKD stages 2, 3a, and 3b, but rarely as stage 5 or kidney failure.

Comparison of eGFR formulas also revealed differences when applied to centenarians. For example, centenarians using the creatinine-based CKD Epidemiology Collaboration (CKD-EPI) formula had lower eGFR than centenarians using the creatinine-based Modification of Diet in Renal Disease (MDRD) formula. Another study found that equations using cystatin C values reported lower eGFR than equations based on serum creatinine.

A further report found that centenarians hospitalized with heart failure had significantly lower eGFR compared with centenarians without evidence of heart failure, suggesting that centenarians with cardiovascular complications may have reduced kidney function. In comparison, a study of centenarians in Hainan Island, one of the areas with the highest life expectancy in China, showed a relatively high median eGFR of 76.42 ml/min per 1.73 m2 (four The quantile interval is 48.62-100.96 ml/min per 1.73 square meters). This higher-than-expected eGFR may be attributed to low levels of cardiometabolic risk factors and the low BMI of the centenarians included in the study.

The lack of longitudinal follow-up of renal function and/or eGFR decline in individuals over 100 years of age limits our understanding of renal changes. However, a cross-sectional comparison among centenarians (age 100-104 years at recruitment), semi-centenarians (age 105-109 years), and supercentenarians (age 110 years and older) found that based on creatinine in Japan There were no substantial differences in the prevalence of CKD among centenarians with CKD calculated using the Society of Nephrology formula eGFR (stages 3b to 5). However, serum cystatin C levels are higher in semi-centenarians and supercentenarians than in centenarians, and the possibility of decreased GFR over 100 years of age cannot be ruled out.

Some studies have reported associations between eGFR or renal function biomarkers and prognosis in centenarians. A study of 86 centenarians in Poland found no significant difference in eGFR between those who died within 180 days of recruitment and those who were alive. However, serum creatinine and cystatin C levels were significantly higher in the non-survivors than in the survivors, suggesting a possible association between these non-specific markers of renal function and mortality. Unfortunately, multivariable analyses adjusting for other cardiovascular risk factors were not possible due to the low sample size. A separate analysis of the prognostic significance of nine inflammatory, cardiac, renal and liver function biomarkers in 1427 Japanese individuals aged 85-115 years found high levels of NT-proBNP, cystatin C and IL -6 and low levels of albumin and cholinesterase were associated with increased risk of all-cause mortality.

Age-related chronic inflammation (also called inflammation) is another potent mediator of kidney aging. Increasing evidence suggests that the accumulation of senescent cells and cells with a senescence-associated secretory phenotype promotes renal fibrosis and chronic inflammation. Furthermore, single-cell analysis demonstrates that senescence of the immune system (e.g., the presence of senescence-associated T cells and age-associated B cells) is causally related to impaired renal regeneration, fibrosis, and inflammation through the formation of tertiary lymphoid structures. Although not yet confirmed in human kidneys, impaired clearance of senescent cells by CD4+ T lymphocytes, monocytes, and macrophages has been reported in the liver, uterus, and endometrium of aged mice. Notably, single-cell transcriptomic analysis of peripheral blood mononuclear cells in supercentenarians found that an increase in cytotoxic CD4+ T cells is a sign of extended human lifespan. Interestingly, cytotoxic CD4+ T cells have been shown to play an important role in eliminating accumulated senescent fibroblasts in human skin. Further research is necessary to elucidate whether these and other immune cells have an active role in slowing kidney aging or exist as a result of the extreme immunosenescence of supercentenarians.

It is important to recognize the practical and ethical limitations of research in this vulnerable population. For example, collecting tissue samples from centenarians is challenging, which limits the application of single-cell or other analyses to discover kidney-specific epigenetic and transcriptomic signatures. Autopsy samples and kidney organoids derived from induced pluripotent stem cells may represent alternative biological resources for studying the aging process in centenarians. A second challenge lies in our ability to elucidate dietary intake throughout an individual's life, which hinders the analysis of optimal proteins and nutrients. Furthermore, few studies have performed urinalysis in centenarians. Given that current formulas are inadequate for estimating GFR in the elderly, adding urinalysis to additional renal function assessments in centenarians may improve our ability to distinguish physiologic renal aging from CKD. ­­

Despite the many challenges, a better understanding of the molecular and cellular basis of renal aging and counterregulatory mechanisms in centenarians may help identify preventive strategies to slow renal aging and reduce the burden of renal disease.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to benefit kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.