Presence of epidermal haemoglobin may explain skin’s defence against ageing and cancer

19th November 2023

The presence of haemoglobin in the skin’s epidermis has been discovered for the first time, offering insight into the skin’s defence mechanisms against ageing and cancer, researchers have announced.

Published in the Journal of Investigative Dermatology, a team from the Keio University School of Medicine in Tokyo sought to determine candidates for unidentified molecules involved in the barrier mechanism by analysing highly expressed genes in the upper epidermis of both humans and mice.

They conducted a comparative transcriptome analysis of the whole and upper epidermis, both of which were enzymatically separated as cell sheets from human and mouse skin.

They found that the messenger RNA level of haemoglobin α, an oxygen carrier in erythroid cells, was enriched in the upper epidermis compared with the levels in the whole epidermis.

To confirm their findings, they then used immunostaining to visualise the presence of haemoglobin α protein in keratinocytes of the upper epidermis.

The researchers also discovered that epidermal haemoglobin was upregulated by oxidative stress and inhibited the production of reactive oxygen species in human keratinocyte cell cultures.

As haemoglobin binds gases such as oxygen, carbon dioxide, and nitric oxide, and is also an iron carrier via the heme complex, it is therefore thought that epidermal haemoglobin is a prime candidate for antioxidant activity and potentially other roles in barrier function.

Professor Masayuki Amagai was lead investigator of the study and professor in the Department of Dermatology at Tokyo’s Keio University School of Medicine, and the Laboratory for Skin Homeostasis at the RIKEN Center for Integrative Medical Sciences, Yokohama.

He said: ’Our findings suggest that haemoglobin α protects keratinocytes from oxidative stress derived from external or internal sources such as UV irradiation and impaired mitochondrial function, respectively.

’Therefore, the expression of haemoglobin by keratinocytes represents an endogenous defence mechanism against skin aging and skin cancer.’

Professor Amagai added: ’Previous studies have identified the expression of various genes with protective functions in keratinocytes during their differentiation and formation of the outer skin barrier.

’However, other barrier-related genes escaped prior detection because of difficulties obtaining adequate amounts of isolated terminally differentiated keratinocytes for transcriptome analysis.’

Dietary flavanols found to improve memory in older adults with poor diet

1st June 2023

A higher intake of dietary flavanols among older adults does not improve memory unless they have a poor diet, according to the findings of a three-year randomised trial.

In the three-year long randomised, double-blind, placebo-controlled trial published in the journal PNAS, researchers tested if a flavanol intervention could improve hippocampal-dependent memory.

The intervention was a cocoa extract containing 500 mg of cocoa flavanols per day. Diet was assessed using the alternative Healthy Eating Index (aHEI) and a urine biomarker was used to measure flavanol intake in a subset of patients. The primary outcome was a change in modified rey auditory verbal learning test – or ModRey – which is used to assess memory. Secondary outcomes included the Flanker task and ModBent, both of which are measures of cognitive function.

Cognitive ageing refers to age-related changes in cognitive function, such as reasoning, memory and processing speed, which typically occur as people get older. Research suggests that areas of hippocampal formation, in particular the dentate gyrus, are implicated in cognitive ageing.

Additionally, it is known that dietary flavanols enhance dentate gyrus function. A three-month randomised, placebo-controlled trial suggested that a flavanol-based dietary interventions may have a beneficial impact on cognitive ageing. Since this was a short-term trial, the US researchers wondered if a higher intake of flavanols over time could positively impact on the memory component of cognitive ageing.

Flavanol intake and improvements to memory

In the recent trial, a total of 3,562 older adults with a mean age of 71 years (66.9% female) were included and randomised to flavanols (1,744) or placebo and followed for three years.

After one year, there were no significant differences in the primary outcome between the two groups (mean difference, MD = 0.08, p = 0.415). Similarly, there were no differences in the two secondary outcomes. In fact, over the following two years, differences in both the primary and secondary outcomes remained non-significant. However, when researchers examined the effect of flavanol intake across aHEI scores, they found a significant improvement in ModRey in those with the lowest tertile aHEI scores (p = 0.011) but not the medium or high tertile.

Based on these findings, the authors suggested that a low intake of flavanols was a potentially important factor driving the hippocampal-dependent component of cognitive ageing.