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Reilly et al. Plast Aesthet Res 2021;8:2 I http://dx.doi.org/10.20517/2347-9264.2020.153 Page 19 of 24

can differ significantly from one region of the body to another. The effects of underlying musculoskeletal
features are more noticeable, e.g., the lack of features across the torso compared to the varied anatomical
structures seen across the face and neck.

In an open-label study on 217 female volunteers, a nutritional supplement (Pure Gold Collagen®) was
tested for its ability to reduce the visible signs of ageing and it was compared to the effects of an aesthetic
surgical intervention, such as Botox, laser treatment or the use of dermal fillers [108] . The study reported
on facial improvements in the nasolabial folds which extend from the side of the nose to the corners of
the mouth. These folds typically deepen with age, and as they are more prominent than other facial lines,
their depth is a useful parameter for measuring the effect of anti-ageing products. A 24% reduction in the
average score from baseline, as determined by an expert visual assessor was reported. In 37% of sub jects, a
significant improvement in nasolabial fold depth was observed, with a reduction of 44% in average score.
Interestingly, a comparable significant decrease in nasolabial fold depth was reported regardless of whether
subjects underwent surgical treatment for nasolabial fold area or not. After 60 days, a decrease in nasolabial
fold depth was observed in subjects who underwent other cosmetic treat-ments, with Dermatologists
reporting a decrease of 15% for laser treatments, 50% for Botox, 28% for fillers, 41% for treatments in the
nasolabial fold area, and an 18% and 10% decrease for mesotherapy and dermabrasion, respectively. In the
group of subjects who had dermabrasion, facial laser treatment, or Botox in the upper area of their face for
glabellar lines or crow’s feet, there was a respective 4%, 12%, and 18% reduction in the visibility of nasola-
bial folds. Not surprisingly, the largest reduction in the number of class 2 wrinkles was observed in subjects
who had fillers in their nasolabial folds (29%). There was also a reduction in class 2 wrinkles among those
who had mesotherapy or platelet-rich plasma therapy (25%). In the group of subjects who had cheek or lip
augmentation by fillers, there was a 25% decrease in class 3 wrinkles.

An independent double-blind, randomised, placebo-controlled clinical trial was performed to investigate
the effects of a collagen-based supplement (Gold Collagen® Forte) on skin elasticity in subjects who
underwent a cosmetic treatment (fillers and Botox in facial areas) and subjects who did not while using this
nutraceutical supplement over a period of 90 days [11,109] . The study showed a statistically significant increase
in skin elasticity after 90 days of treatment and an increase in skin elasticity was observed singularly both
in subjects who underwent a cosmetic treatment and subjects who did not. Moreover, no significant
change in skin elasticity was observed in the placebo group, both in subjects who underwent or did not
undergo a cosmetic treatment. The increase in skin elasticity suggests that this functional food supplement,
containing collagen peptides among other active ingredients, has an effect in restoring the correct levels
of extracellular matrix proteins such as collagen and elastin. Also, the results revealed a reduction in solar
elastosis and in hyperkeratosis in the dermis.

FUTURE PERSPECTIVES AND OPPORTUNITIES
Future possibilities for improving collagen synthesis, fibril formation, ECM integrity and skin ageing
depend on the on the activity of the fibroblast cell. However, with time, wear and tear, oxidative damage
and other cellular influences, the fibroblast becomes senescent, i.e., loses the ability to replicate (replicative
senescence). As the fibroblast ages, there is a decrease in telomeres (telomeres are DNA tandem repeats
found at the end of chromosomes and known to shorten with each progressive cycle of cell division).
Although they remain metabolically active, the senescent fibroblasts experience a decline in their normal
cellular functions. Inflammation and cumulative damage are associated with increased telomere shortening,
which can be used as a biomarker of cellular senescence, genomic instability and cell ageing in skin of
older individuals [110] . This leads to a situation where the skin is not capable of efficiently repairing damaged
collagen, with a consequent loss of a functional support matrix related to the visible signs of ageing, such as
fines lines, wrinkles and sagging.