Serum albumin, a large protein made in the liver and released into the bloodstream, is one of the most important biomarkers of aging, according to deep-learner predictors of biological age.
Physiological function of albumin
Albumin plays a crucial role in maintaining fluid balance and transporting molecules in the body, such as hormones, vitamins or enzymes. Albumin’s functions include blood pressure maintenance, molecular transport, antioxidant defense, pH maintenance, inflammatory control, cell growth and development, and protein storage.
The large size and negative charge of albumin attracts water, which enables it to maintain colloid osmotic pressure in the circulatory system. Additionally, albumin is a scavenger of free radicals, performing an antioxidant function and transporting metals to areas where they work as enzyme co-factors. Albumin also has binding sites that enable the transport of drugs and hormones such as testosterone. This function is often exploited by bioengineers and pharmaceutical companies as a mechanism for drug delivery.
Another interesting characteristic of albumin is that its shape can be altered by shifts in pH, which the body uses to neutralize oxidizing compounds.
Albumin and aging
Albumin blood tests can test the function of liver and kidney. Generally, albumin levels peak at 20 years old and then decrease with age. Females show a more rapid decline in albumin than men, although this stabilises to the same levels around age 60.
Studies have shown that serum albumin levels sharply decrease with age. Values less than 3.8 grams per deciliter are associated with increased morbidity, mortality, and disability in the elderly. It is also a key indicator of chronic kidney and liver disease.
Aging biomarkers may often represent associations with aging (such as white hairs or wrinkles) instead of providing a causal relationship. However, a study performed by an insurance company comprising millions of individuals, has shown that levels of serum albumin might be predictive of overall mortality. People with the highest average serum values for their age groups had the lowest risk of mortality, while individuals with the lowest serum albumin values had the highest risk of mortality. The presence of albumin in the urine, which is normally undetectable by conventional semi-quantitative tests, is considered an early marker of kidney damage and is associated with an increased progression of kidney disease. It is also an independent risk factor for the development of cardiovascular disease. Long-term use of pentoxifylline (Trental) reduces albuminuria and loss of glomerular filtration quality in diabetic and non-diabetic kidney disease (especially in the elderly). Due to these properties, pentoxifylline prevents a decrease in the level of soluble Klotho protein, which prevents the development of many diseases of the elderly.
Factors that affect serum albumin
A variety of factors can alter the levels of serum albumin. On the one hand, there are lifestyle factors such as hydration, nutrition or exercise, while other physiological factors include certain diseases or conditions.
Amongst the lifestyle factors, amino acid availability or protein intake can alter the synthesis of albumin. Higher protein intake is associated to decreased serum albumin, suggesting protein restriction might suppose a healthier diet. However, in healthy individuals it has been suggested the effect is almost negligible.
A study has suggested that sarcopenia (age-related muscle loss) is associated to levels of serum albumin in the elderly. Nonetheless, in a young population, weight training did not show to affect significantly serum albumin.
Certain conditions such as type 2 diabetes, and chronic kidney, liver or heart damage have shown to increase levels of serum albumin. Inflammaging, the chronic inflammation associated to age, is also a factor associated to decreased levels of albumin.
- ↑ http://www.aging.ai
- ↑ Weaving, G., Batstone, G.F. and Jones, R.G. (2015) “Age and sex variation in serum albumin concentration: An observational study,” Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 53(1), pp. 106–111. Available at: https://doi.org/10.1177/0004563215593561.
- ↑ R. N. Baumgartner, K. M. Koehler, L. Romero, and P. J. Garry, “Serum albumin is associated with skeletal muscle in elderly men and women,” Am. J. Clin. Nutr., vol. 64, no. 4, pp. 552–558, Oct. 1996
- ↑ M. Fulks, R. Stout, and V. Dolan, “Albumin and all-cause mortality risk in insurance applicants,” J. Insur. Med., vol. 42, no. 1, pp. 11–17, 2010
- ↑ Ljungman, S., Wikstrand, J., Hartford, M., & Berglund, G. (1996). Urinary albumin excretion—a predictor of risk of cardiovascular disease: a prospective 10-year follow-up of middle-aged nondiabetic normal and hypertensive men. American journal of hypertension, 9(8), 770-778. PMID: 8862223 DOI:10.1016/0895-7061(96)00102-1
- ↑ Navarro-González, J. F., Mora-Fernández, C., de Fuentes, ... & García, P. (2015). Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. Journal of the American Society of Nephrology, 26(1), 220-229. PMID 24970885 PMC 4279740 DOI:10.1681/ASN.2014010012
- ↑ Chang, K., Li, Y., Qin, Z., Zhang, Z., Wang, L., Yang, Q., & Su, B. (2023). Association between Serum Soluble α-Klotho and Urinary Albumin Excretion in Middle-Aged and Older US Adults: NHANES 2007–2016. Journal of Clinical Medicine, 12(2), 637. https://doi.org/10.3390/jcm12020637
- ↑ Fernandez-Fernandez, B., Valino-Rivas, L., Sanchez-Nino, M. D., & Ortiz, A. (2020). Albuminuria downregulation of the anti-aging factor klotho: the missing link potentially explaining the association of pathological albuminuria with premature death. Advances in therapy, 37(2), 62-72. PMID 32236874 DOI:10.1007/s12325-019-01180-5
- ↑ Navarro-González, J. F., Sánchez-Niño, M. D., Donate-Correa, J., Martín-Núñez, E., Ferri, C., Pérez-Delgado, N., ... & Mora-Fernández, C. (2018). Effects of pentoxifylline on soluble klotho concentrations and renal tubular cell expression in diabetic kidney disease. Diabetes Care, 41(8), 1817-1820. PMID:29866645 DOI:10.2337/dc18-0078
- ↑ P. De Feo, F. F. Horber, and M. W. Haymond, “Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans,” Am. J. Physiol. Metab., vol. 263, no. 4, pp. E794–E799, Oct. 1992
- ↑ S. Sarwar and R. A. Sherman, “How Well Does Serum Albumin Correlate with Dietary Protein Intake in Dialysis Patients?,” Kidney Int. reports, vol. 2, no. 1, pp. 90–93, Sep. 2016
- ↑ Baumgartner, R.N. et al. (1996) “Serum albumin is associated with skeletal muscle in elderly men and women,” The American Journal of Clinical Nutrition, 64(4), pp. 552–558. Available at: https://doi.org/10.1093/ajcn/64.4.552.
- ↑ D. G. Levitt and M. D. Levitt, “Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements,” Int. J. Gen. Med., vol. 9, pp. 229–255, Jul. 2016