m130 wrote:I have been wondering for years if using retinoids to increase cell turnover somehow hastens their eventual death, like if the skin cells can only reproduce a certain # of times and then crap out. I guess these products have been around long enough to tell by now, or if this effect happens, it would be in our 90s and hopefully we wouldn't care anymore by then.
Very doubtful. What happens in the petri dish is not the same as what happens in the living organism. This is going to be a long post.
First, about the applicability of the Hayflick limit to renewing tissues, such as the basal layer of the skin:
ref: Nat Biotechnol. 2003 Mar;21(3):229-30.
"The absence of telomerase in cultured human cells and the shortening of telomeres at each population doubling have suggested that telomere length acts as a mitotic clock that accounts for their limited lifespan.
"
More careful study, however, has revealed telomerase activity in stem cells and some dividing transit cells of many renewing tissues
"It now seems likely that telomerase is active in vivo where and when it is needed to maintain tissue integrity."
Second, some findings on the long-term use of tretinoin. It seems that the more you use it, and the longer you use it, the better condition your skin will be in. Use it to tolerance, and include a good sunscreen.
ref: J Am Acad Dermatol. 2005 Nov;53(5):769-74.
"Improvement in epidermal cellular atypia is consistent with the ability of RA (retinoic acid, or tretinoin) to act as a chemopreventive agent in epithelial carcinogenesis. Prolonged use also significantly increased collagen matrix deposition in dermal repair zones, which most likely contributes to wrinkle effacement by RA."
ref: J Am Acad Dermatol. 1997 Mar;36(3 Pt 2):S27-36.
"After 12 months of treatment, there were additional signs of tissue normalization including deposition of new collagen in the papillary dermis and ultrastructural evidence of dermal reconstruction with improvement in the dermoepidermal junction and correction of keratinocyte degeneration, changes that presumably relate directly to tretinoin's mechanism of action. There was no suggestion of cytologic atypia in these studies or in biopsy specimens obtained after up to 4 years of continued use. Mild to moderate dermatitis was the only common adverse reaction to tretinoin use... Thus, topical tretinoin is safe and effective in the treatment of photodamage."
ref: Int J Dermatol. 1998 Apr;37(4):286-92.
"As treatment is continued beyond 24 months, the collagen organization continues to improve and elastosis continues to decrease. Increases in epidermal and dermal mucin and decreases in epidermal melanin are consistent throughout the treatment period. The reduction in the hyperpigmentation of photodamage is comparable with the histologic and clinical improvements seen when tretinoin is used to treat conditions such as melasma. No adverse effects on the histopathology of the skin are noted with long-term exposure to tretinoin. Neither keratinocyte nor melanocyte atypia is detected. "
ref: Am J Clin Dermatol. 2005;6(4):245-53.
"Treatment with tretinoin resulted in significantly greater improvement relative to placebo in clinical signs of photodamage (fine and coarse wrinkling, mottled hyperpigmentation, lentigines, and sallowness), overall photodamage severity, and investigator's global assessment of clinical response (p<0.05). Histologic evaluation showed no increase in keratinocytic or melanocytic atypia, dermal elastosis, or untoward effects on stratum corneum following treatment with tretinoin compared with placebo. Immunohistochemistry studies, conducted at three study centers, showed a significant increase relative to placebo in facial procollagen 1C terminal, a marker for procollagen synthesis, at month 12 (p=0.0074). CONCLUSION: Long-term treatment with tretinoin emollient cream 0.05% is safe and effective in subjects with moderate to severe facial photodamage."
