In this brief overview I will review some of the ways in which free radicals and related highly reactive species are produced in biological systems. I will discuss the reactivities and lifetimes of these species, and also will briefly list some pathological conditions and chronic diseases in which these species may be involved. The rich variety of the species of interest in free radical biology is notewor­ thy. Table 1 lists species that have been implicated in various physiological and pathological processes; some of these are neutral radicals, some are radical ions, and some are molecules that contain an even number of electrons and, therefore, are not free radicals. As we shall see, radicals differ greatly in their stabilities; one of the radicals listed in Table 1, nitrogen dioxide, is sufficiently stable to reach ppm levels in polluted urban air. What name can be used to encompass the species listed in Table I? A phrase that is finding increased use in free radical biology is "partially reduced oxygen products." However, even this broad title is unsatisfactory since some of the species in Table 1 contain oxygen atoms at the same oxidation level as elemental oxygen (e.g. ozone and singlet oxygen). The property that these species share is that they have the potential to cause radical reactions to occur in biological systems. Some of these species are radicals and therefore react by radical processes; others react to produce molecules that can decompose to form radicals (e.g. singlet oxygen leads to hydroperoxides). However, these species need not always react via free radical pathways. For example, ozone, hydrogen

Oxy-radicals and related species: their formation, lifetimes, and reactions.

http://scholarcommons.sc.edu/cgi/viewcontent.cgi?article=1143&context=chem_facpub

Effect of collagen turnover on the accumulation of advanced glycation end products.

Normal structure and function of the lung parenchyma depend upon elastic fibers. Amorphous elastin is biochemically stable in vitro, and may provide a metabolically stable structural framework for the lung parenchyma. To test the metabolic stability of elastin in the normal human lung parenchyma, we have (a) estimated the time elapsed since the synthesis of the protein through measurement of aspartic acid racemization and (b) modeled the elastin turnover through measurement of the prevalence of nuclear weapons-related 14C. Elastin purified by a new technique from normal lung parenchyma was hydrolyzed; then the prevalences of D-aspartate and 14C were measured by gas chromatography and accelerator-mass spectrometry, respectively. D-aspartate increased linearly with age; Kasp (1.76 x 10(-3) yr(-1) was similar to that previously found for extraordinarily stable human tissues, indicating that the age of lung parenchymal elastin corresponded with the age of the subject. Radiocarbon prevalence data also were consistent with extraordinary metabolic stability of elastin; the calculated mean carbon residence time in elastin was 74 yr (95% confidence limits, 40-174 yr). These results indicate that airspace enlargement characteristic of "aging lung" is not associated with appreciable new synthesis of lung parenchymal elastin. The present study provides the first tissue-specific evaluation of turnover of an extracellular matrix component in humans and underscores the potential importance of elastin for maintenance of normal lung structure. Most importantly, the present work provides a foundation for strategies to directly evaluate extracellular matrix injury and repair in diseases of lung (especially pulmonary emphysema), vascular tissue, and skin.

/pdf/marked-longevity-of-human-lung-parenchymal-elastic-fibers-493ty15eqs.pdf

Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon.

Age estimation in cadavers, human remains and living individuals may clarify issues with significant legal and social ramifications for individuals as well as for the community. In such cases methods for estimating age should fulfil the following specific demands: (1) they must have been presented to the scientific community, as a rule by publication in peer-reviewed journals, (2) clear information concerning accuracy of age estimation by the method should be available, (3) the methods need to be sufficiently accurate and (4) in cases of age estimation in living individuals principles of medical ethics and legal regulations have to be considered. We have identified and summarized the methods that essentially fulfil these specific demands. In childhood and adolescence morphological methods based on the radiological examination of dental and skeletal development are to be recommended. In adulthood, the accuracy of most morphological methods is much reduced. Here a biochemical method based on aspartic acid racemization in dentine provides the most accurate estimates of age, followed by special morphological dental and skeletal methods. The choice of method has to take account of the individual circumstances of each case. Most methods require either the consultation of specialised and trained scientists or an adequate calibration by the “user”. Very few attempts have been made to find common standardisation, calibration and evaluation procedures or to develop means of quality assurance for methods of age estimation. Efforts in these directions are necessary to guarantee quality standards and adequate answers to the important legal and social issue of age estimation in forensic medicine.

Age estimation: the state of the art in relation to the specific demands of forensic practise.

Recently, a substantial amount of free d-serine has been demonstrated in rat brain, although it has long been presumed that d-amino acids are uncommon in mammals. The anatomical distribution and age-related changes in endogenous d-serine have been examined here to obtain insight into its physiological functions. Free d-serine exclusively occurs in brains, with a persistent high content from birth to at least 86 postnatal weeks. The patterns of the regional variations and the postnatal changes in brain d-serine are closely correlated with those of the N-methyl-d-aspartate (NMDA)-type excitatory amino acid receptor. Because d-serine potentiates NMDA receptor-mediated transmission by selective stimulation of the strychnine-insensitive glycine site of the NMDA receptor, it is proposed that d-serine is a novel candidate as an intrinsic ligand for the glycine site in mammalian brain.

Endogenous d‐Serine in Rat Brain: N‐Methyl‐d‐Aspartate Receptor‐Related Distribution and Aging

An age-related accumulation of D-aspartic acid was detected in the white matter of ten normal brains from individuals aged 30 to 80 years. Gray matter showed no systematic increase in D-aspartic acid. The rate constant for D-aspartate formation in the brain is equal to the predicted value calculated for 37 degrees C. Accumulation of the uncommon D-aspartate isomer in myelinated white matter implies that there is little or no turnover of this tissue, and this may have a bearing on dysfunction of the aging brain or on other diseases of myelin.

https://science.sciencemag.org/content/sci/220/4604/1407.full.pdf

Jonathan Burg

Papers

Accumulation of D-Aspartic Acid with Age in the Human Brain