A Potential Oxidative Biomarker of Aging in Urine
Since aging is caused by a collection of distinct, interacting processes of damage accumulation and reactions to that damage, it is unlikely that there will ever exist one, unified, undisputed measure of biological age. All present candidate measures of aging are composites of many individual metrics, even the epigenetic clock, which is a specific pattern of many different DNA methylation locations in the genome. New, simple biomarkers of aging that reflect one process or aspect of age-related degeneration are still of interest, however, as they might turn out to improve existing combined measures of aging if added into the mix. So researchers continue to work in this area of development, turning out results such as the data presented in this open access paper.
The rate of aging differs among individuals due to variations in the genetic and environment background. Chronological age, which is simply calculated according to birth date, is an imprecise measure of biological aging. The disconnection between chronological age and lifespan has led to a search for effective and validated biomarkers of aging. A good aging biomarker should be based on mechanisms described by major theories of aging, which mainly include oxidative stress, protein glycation, DNA methylation, inflammation, cellular senescence and hormonal deregulation. The current consensus is that aging is driven by the lifelong gradual accumulation of a broad variety of molecular faults in the cells and tissues.
Any error occurring on a DNA template or in messenger RNA will eventually lead to the production of abnormal proteins. However, the exposure of a double-stranded DNA chain or single-stranded RNA chain to free radicals, which are by-products of normal metabolism, can cause oxidative damage to biomolecules. 8-Oxo-7,8-dihydro-2′-deoxyguanine (8-oxodGsn) is by far the most studied DNA oxidative product. Similarly, mismatch of 8-oxo-7,8-dihydroguanine (8-oxoGsn) in RNA leads to transcriptional errors and produces abnormal protein. These excision products can be transported across the cell membranes and excreted into cerebrospinal fluid, plasma, and urine without any further metabolism.
Under the free radical theory of aging, urinary 8-oxodGsn and 8-oxoGsn are molecules that may reflect the oxidative state of the whole body rather than a specific organ, and these are promising biomarkers of aging. We previously established a liquid chromatography-mass spectrometry system and determined the oxidized nucleosides in senescence-acceleration-resistant mouse 1 (SAMR1), demonstrating that the measurement of 8-oxoGsn in urine had potential as a novel means of evaluating the aging process. In the present study, we applied this procedure to human urine samples to see if such samples can be used to estimate the physiologic age.
We have taken a keen interest in the relationship between oxidation markers and age. Most previous studies have reported a rise in the urinary 8-oxodGsn level with age. Our previous study showed an age-dependent increase in the two biomarkers in mice, rats and monkeys. In the present study, the same trend was noted in humans. Compared with other studies, the current studies covered larger range of ages, from neonates to 90-year-olds. The lowest 8-oxodGsn and 8-oxoGsn levels appeared in the young adults (11-30 years of age). As people age, the antioxidant defense systems degenerate, and the levels of 8-oxodGsn and 8-oxoGsn increase gradually until the end of life.
To date, most studies have dealt with urinary 8-oxodGsn, and a very limited number of studies have focused on 8-oxoGsn. Our study demonstrated that 8-oxoGsn is a better aging marker than 8-oxodGsn in two respects. First, the level of 8-oxoGsn was higher (approximately 2-fold) than 8-oxodGsn in age-matched counterparts. Second and more importantly, the levels of 8-oxoGsn correlated better with the rate of aging. The 8-oxoGsn content does not always correlate with chronological aging but instead reflects the actual physiological stage of aging.