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Page 14 of 24 Reilly et al. Plast Aesthet Res 2021;8:2 I http://dx.doi.org/10.20517/2347-9264.2020.153

Figure 10. Advanced Glycation End product (AGE) are formed when sugars such as glucose or pentose react with lysine residues in the
collagen backbone, eventually leading to generation of either non-crosslinking type AGE species such as CML, or crosslink type AGE
such as pentosidine. (By permission of MINERVA Research Labs Ltd - London)

with cumulative oxidative stress, the combination of glycation and oxidation forms irreversible adducts
with the protein which ultimately become AGE, specifically as carboxymethyllysine and pentosidine
[40]
adducts [Figure 10] . In a distinct but related mechanism, ALE involving polyunsaturated fatty acids as a
primary target for free radical attack, leads to production of lipid peroxy radicals, lipid hydroperoxides and
aldehyde products [Figure 11]. Malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) are key lipid
oxidation products and can react with free amino groups of the collagen protein, once again predominantly
lysine as the other classic amino acids that are susceptible to react with MDA and 4-NHE (histidine and
[71]
cysteine) are not present in collagen at significant levels . Due to the slow turnover of collagen, the
damage can accumulate over years and decades. The cumulative damage of the collagen proteins in the
ECM due to ALE and AGE species disrupts their normal structure and metabolism and leads to increased
stiffness and rigidity and loss of function.

Using a well-balanced combination of both water-soluble and lipid-soluble antioxidants in supplements
formulated to deliver optimal absorption, vascular distribution and cellular bioavailability, it is possible to
delay skin ageing and to improve skin conditions .
[80]

ANTI AGEING STRATEGIES RELATED TO SKIN COLLAGEN
It has been reported that skin health and beauty are principal factors representing overall wellbeing and the
[81]
associated perception of health in consumers . The distinctions between chrono-aged skin (which tends
to be thin, dry and finely wrinkled) and photo-aged skin (which tends to be thickened, hyperpigmented,
deeply wrinkled and exhibiting a rough profilometric topography) allows targeted intervention strategies to
be devised. The MacArthur Foundation Study of Successful Aging was hailed as the “new gerontology” and
advocated the potential for a healthy and engaged old age [82,83] . This is an alternative view to the older “decline
and loss” paradigm that views ageing as a series of individual decrements or losses to which both elders