The free radical theory of ageing as originally proposed by Harman as early as 1956 states that organisms/organs age because cells accumulate free radical damage over time [4]. Today, it is one of the most widely accepted theories used to explain mechanisms underlying the ageing process, including the hair follicle.
Free radicals are highly reactive molecules with unpaired electrons that can directly damage various cellular structural membranes, lipids, proteins and DNA. The damaging effects of these reactive oxygen species are induced internally during normal metabolism and externally through exposure to various oxidative stresses from the environment. The body possesses endogenous defence mechanisms, such as anti-oxidative enzymes (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic anti-oxidative molecules (vitamin E, vitamin C, glutathione, ubiquinone), protecting it from free radicals by reducing and neutralizing them. With age, the production of free radicals increases, whereas the endogenous defence mechanisms decrease. This imbalance leads to the progressive damage of cellular structures, presumably resulting in the ageing phenotype.
Ageing-related loss of hair follicle stem cell marker expression starts well before hair follicles have shortened. Using genomic instability syndromes and exposure to ionizing radiation as models, Nishimura proposed an accumulation of DNA damage to be involved in the ageing process (oral communication on the occasion of 7th World Congress for Hair Research, 4–6 May 2013, Edinburgh, Scotland)
Recent studies on the evolution of androgenetic hair loss have focused on oxidative stress:
Naito et al. analyzed the effect of the lipid peroxides on hair follicles and observed that the topical application of linolein hydroperoxides, one of the lipid peroxides, lead to the early onset of the catagen phase in murine hair cycles. Furthermore, they found that lipid peroxides induced apoptosis of hair follicle cells. They also induced apoptosis in human epidermal keratinocytes by upregulating apoptosis-relatedgenes. These results indicate that lipid peroxides, which can cause free radicals, induce the apoptosis of hair follicle cells, and this is followed by early onset of the catagen phase.
Bahta et al. cultured dermal hair papilla cells (DPC) from balding and non-balding scalp and demonstrated that balding DPCs grow slower in vitro than non-balding DPCs. Loss of proliferative capacity of balding DPCs was associated with changes in cell morphology, expression of senescence-associated betagalactosidase, decreased expression of proliferating cell nuclear antigen and Bmi-1, upregulation of p16(INK4a)/pRb, and nuclear expression of markers of oxidative stress and DNA damage including heat shock protein-27, superoxide dismutase catalase, ataxia-telangiectasia-mutated kinase (ATM), and ATM- and Rad3-related protein. The findings of premature senescence of balding DPC in vitro in association with expression of p16(INK4a)/pRB suggests that balding DPCs are particularly sensitive to environmental stress.
Works Cited:
Trüeb, R. M. (2015), The impact of oxidative stress on hair. Int J Cosmet Sci, 37: 25–30. doi:10.1111/ics.12286
Karnik, P., Shah, S., Dvorkin-Wininger, Y., Oshtory, S. and Mirmirani, P. Microarray analysis of androgenetic and senescent alopecia: comparison of gene expression shows two distinct profiles. J. Dermatol. Sci. 72, 183–186 (2013)
