Studies on Age Pigments Evolving Into a New Theory of Biological Aging

Abstract

A variety of age pigment-like fluorophores have been recognized, identified and investigated during the past three decades. They are mainly the end-products of various side-reactions of essential biological processes. Among these, the lipid peroxidation-related fluorophores formed via aldehyde-protein crosslinking are of general importance. Fluorescent advanced glycation end-products formed during glycation/Maillard reactions, are oxygen independent, carbohydrate-associated age pigment-like substances. Age pigments, particularly those identified in retinal pigment epithelium, represent another type of age pigment that originates from polyenic biomolecules, including retinoids and carotenoids. Various αβ-unsaturated aldehydes can also react with the amino groups of nucleotides to induce biological alteration. Although age pigments can be produced from different types of biological materials, the crosslinking of carbonyl and amino compounds is a common toxiferous process during biological life. In the context of various aging phenomena and degenerative diseases, this process may constitute an essential mechanism of aging --- the carbonyl toxification process of biological aging.

The proteasomal system

“…Examples are the ceroid lipofuscinoses with their decline in proteolytic capacity (Weimer et al, 2002;Holopainen et al, 2001). Due to the prolonged half-life and the exposure to external influences such primary protein aggregates are transferred into a highly cross-linked and reactive material, referred to as lipofuscin, ceroid or AGE-pigment-like fluorophores (Yin, 1996;Yin, 1995). During this process such material might be several times taken up into lysosomes and released by disrupting them.…”

A possible new role for the anti-ageing peptide carnosine

“…3). First it is noteworthy that lipofuscin, the fluorescent age pigment, is found primarily in carnosine-rich tissues such as nerve, muscle and brain [33]. Thus it is possible that the reaction of carnosine with the protein carbonyls might create a relatively inert form of lipofuscin [33,34].…”

“…First it is noteworthy that lipofuscin, the fluorescent age pigment, is found primarily in carnosine-rich tissues such as nerve, muscle and brain [33]. Thus it is possible that the reaction of carnosine with the protein carbonyls might create a relatively inert form of lipofuscin [33,34]. Our preliminary studies [unpublished data] show that the reaction of carnosine with a protein glycated with acrolein (another source of protein carbonyls) [35] induces a change in the fluorescent properties of the protein-acrolein adduct.…”

Relationships between antioxidants, antioxidant enzyme activities and lipid peroxidation products during early development in Dentex dentex eggs and larvae

“…These reactions also produce lipid peroxide related fluorophores, such as lipofuscin, which are collectively termed lipid-soluble fluorescent products (LSFP), formed by aldehyde-protein crosslinking of carbonyl and amino groups, which are common in biology and as they have also been related to the aging process are sometimes termed fluorescent age pigments (FAP) (Sohal and Wolfe, 1986;Sohal and Brunk, 1990;Yin, 1995).…”