The document discusses the latest advances in translational anti-aging skin research, emphasizing the role of personalized genomics and skin profiling in improving skin health and responsiveness to products. It outlines various scientific developments, including genomic disease profiling, skin microbiomics, and advanced treatments like cellular therapies and retinoid substitutes. Additionally, it highlights opportunities for commercialization in anti-wrinkle solutions and technologies transitioning from military to aesthetic applications.

1. Translational anti-aging skin research: latest advances, personal genomics, and product research opportunities Melanie Swan Founder DIYgenomics +1-650-681-9482 @DIYgenomics www.DIYgenomics.org [email_address] 11th Symposium of LVMH Recherche October 27, 2011, London UK Slides: http://slideshare.net/LaBlogga

2. About Melanie Swan Founder DIYgenomics, futurist and applied genomics expert Work experience: Fidelity, JP Morgan, iPass, RHK/Ovum, Arthur Andersen Education: MBA Finance, Wharton, University of Pennsylvania; BA French and Economics, Georgetown University Sample publications: Source: http://melanieswan.com/publications.htm Swan M. Meeting Report: American Aging Association 40(th) Annual Meeting, Raleigh, North Carolina, June 3-6, 2011. Rejuvenation Res . 2011, Aug;14(4):449-55. Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med . 2010, Dec 23; 2:e20. Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010 , May;12(5):279-88. Swan, M. Translational antiaging research. Rejuvenation Res. 2010 , Feb;13(1):115-7. Swan, M. Engineering Life into Technology: the Application of Complexity Theory to a Potential Phase Transition of Intelligence. Symmetry 2010 , 2, 150:183. Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009 , 2, 492-525.

3. Agenda Top 10 translational anti-aging skin research advances Role of personalized genomics Skin disease profiling Skin wellness profiling Skin care product response Wrinkles: potential causes and translational remedies Other translational anti-aging skin advances Image credit: http://www.hongkiat.com

4. Top 10 anti-aging skin research advances Botox substitutes Skin microbiomics 3-D skin printing Next-generation skin grafting Cellular therapies Genomic disease profiling Genomic product profiling Retinoids and substitutes Spray-on skin Stem cell facelift 2020 2010 2015 Image credit: http://www.dreamstime.com

5. Agenda Top 10 translational anti-aging skin research advances Role of personalized genomics Skin disease profiling Skin wellness profiling Skin care product response Wrinkles: potential causes and translational remedies Other translational anti-aging skin advances Image credit: http://www.hongkiat.com

6. Personalized genomics and skin research Using genetic sequencing profiles of individuals in health and wellness decisions Multilevel analysis Whole human sequencing, SNP mutations, structural variation, epigenomics, RNA expression, microbiome integration Consumer cost = $99 International availability 100,000+ subscribers Image credit: http://snpsinfo.synthasite.com SNP mutation

7. Numerous useful applications of genomics Ancestry Carrier status (pregnancy) Identity (paternity, forensics) Drug response U.S. FDA has validated genomic biomarkers for 75 drugs (July 2011) 1 Disease risk Criticism re: validity and utility 2 Image credit: http://www.uchsc.edu 1 Source: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm 2 Source: Swan M. Multigenic condition risk assessment in direct-to-consumer genomic services. Genet Med. 2010 May;12(5):279-88.

8. Personal genome results

9. Drug response

10. Example: what to do with your data Check if you have the risk allele for the BDNF gene Determine related SNP/rsID#, rs6265 (neuroplasticity) Search genomic data for rs6265 genotype (e.g., CC) Determine the risk allele (which letter?) (e.g.; G 1 ) Current genomics search resources PharmGKB, dbSNP, GWAS catalog, SNPedia Source: http://www.wired.com/wiredscience/2009/10/genetically-bad-driving 1 Ribeiro, L. et. Al., The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. Cellular, Molecular and Developmental Neuroscience. May 8, 2007.

11. Finding your BDNF data, variant rs6265 Consumer genomic services genotype 1 million variants but only map a few up to the annotation browser

12. Health optimization studies Goal: realize predictive preventive medicine Optimize individualized care and product recommendations Generalized hypothesis One or more polymorphisms may result in out-of-bounds baseline levels of phenotypic markers. These levels may be improved through personalized intervention. Skin study examples: TERC & TERT/telomere-length, IL1A and TNF genes/Retin-A reaction Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med. 2010, Dec 23; 2:e20. Genotype Phenotype Intervention Outcome + + =

13. Genomic disease profiling: skin cancers Melanoma: 20% heritability (vs. 33% non-skin cancers) Source: DIYgenomics Consumer genomic service coverage of skin cancer conditions

14. Personalized genetic risk for melanoma Source: DIYgenomics, Swan M. Multigenic condition risk assessment in direct-to-consumer genomic services. Genet Med. 2010 May;12(5):279-88. Polygenic risk analysis for melanoma

15. Basal and squamous cell carcinoma Source: DIYgenomics Polygenic risk analysis for basal cell carcinoma Polygenic risk analysis for squamous cell carcinoma

16. Genomic profiling for other skin disease Skin irritation disease Acne, eczema (atopic dermatitis), irritation, dryness, psoriasis, erythema Sun damage and pigmentation Sun damage, premature aging, freckles, xeroderma pigmentosa, solar lentigo, skin lesions, vitiligo Rare genetic and other skin disease Cockayne syndrome, Kindler syndrome, Dupuytren's disease, scleroderma (limited cutaneous type), keloid (scarring) Source: DIYgenomics Image credit: http://www.umich.edu

17. Genomic disease profiling in hair conditions Hair loss, male pattern baldness, alopecia areata Premature hair graying Hair thickness and curliness Source: DIYgenomics, https://www.23andme.com/health/Male-Pattern-Baldness/techreport/

18. Genomic wellness profiling in skin Predictive indicator for which skin conditions may arise over time Areas of genomic wellness profiling Cancer: oncogenes and tumor suppressors Immune system response (photo-damage: melanin production, p53, TIMP 1 ) DNA damage repair response Subcutaneous fat thickness Overall aging response Other dermis and epidermis wellness factors Image credit: http://www.dnacustomizednutrition.com 1 tissue inhibitor of metalloproteinases

19. Genomic product response profiling in skin Personalized product recommendations Predicted response Efficacy Side effects Skin care products with genomic associations Tretinoin (P&G, Kaczvinsky JR et al, Skin Therapy Lett, 2011) Antioxidant treatment Anti-aging DHEA treatment Aluminum powder Mosquito repellent ( microbiomics) ( Verhulst NO et al, FEMS Microbiol Ecol, 2010) Image credit: http://www.dkorean-beauty.com

20. Skin microbiome profiling Bacterial colonization influenced by host and environment 2-way immune response Microbiota educates immune system Cutaneous innate and adaptive immune responses modulate skin microbiota Novel promicrobial and antimicrobial treatments ( Grice EA et al, Nat Rev Microbiol, 2011) Image credit: Grice EA et al, Nat Rev Microbiol, 2011, Figure 3 Skin microbiome ecosystem distribution

21. Agenda Top 10 translational anti-aging skin research advances Role of personalized genomics Skin disease profiling Skin wellness profiling Skin care product response Wrinkles: potential causes and translational remedies Other translational anti-aging skin advances Image credit: http://www.hongkiat.com

22. Wrinkle formation: potential causes Sun damage and UV-radiation Activation of heparanase (an extracellular matrix (ECM) degradation molecule Loss of subcutaneous fat Fibrosis Tissue thickened and loosened from ECM proteins Telomere shortening Photo-damage reduces telomere length and increases reactive oxygen species (ROS) production Image credit: http://cfps.gorillartsgroup.com Loss of subcutaneous fat with aging

23. Wrinkles: potential translational solutions Topical treaments Retinoids Retinoid substitutes Salicin CoQ10 Intense pulsed light (IPL) treatment for photo-aging Cellular therapies LaViv fibroblast culturing and nasolabial injection Facial fat transfer / stem cell facelift Fillers (e.g.; botox) and substitutes Transdermal hexapeptides and microneedle array Image credit: http://www.stockpodium.com

24. Topical treatment of wrinkles - retinoids Any of various natural or synthetic derivatives of vitamin A Retinol, retinaldehyde, adapalene, tretinoin, isotretinoin, tazarotene Retin-A is a popular tretinoin product Image credit: http://www.skinacea.com/retinoids/types-of-retinoids.html

25. DIYgenomics Retin-A skin cream study Widely-used Retin-A often produces side-effects Source: http://genomera.com/studies/retin-a-wonder-cream-for-acne-and-wrinkles-is-there-a-genomic-link

26. Retinoid substitutes Retinoid limitations Photo-unstable and skin irritation Retinyl retinoate (a novel hybrid retinoid) An ester of all-trans retinoic acid (RA) and all-trans retinol Reduced toxicity due to blocking carboxyl end group of RA Higher skin regeneration activity than with retinol Increases the stability of retinol which may have an anti-wrinkle effect ( Kim H et al, Br J Dermatol, 2010 ) Retinyl N-formyl aspartamate A synthesized photostable retinol derivative with a similar effect on collagenase expression level as retinol (Lee MS et al, J Am Acad Dermatol, 2006) Image credit: http://www.enprani.com Enprani retinyl retinoate-based product

27. Additional topical treatments of wrinkles Salicin (willow bark-derived anti-inflammatory) Activates heat shock proteins (HSPs) which protect cells from stress-induced damage (Gopaul R et al, J Cosmet Dermatol, 2010) CoQ10 Reduces reactive oxygen species (ROS) production and DNA damage triggered by UV-radiation (Inui M et al, Biofactors, 2008) Intense pulsed light (IPL) treatment for photo-aging Prevents telomere shortening and decreases ROS (Wang R et al, Photomed Laser Surg, 2011) Image credit: http://www.luckyvitamin.com

28. DIYgenomics TA-65 study Skin benefits: look younger, improved wound healing, less sleep but improved quality (de Jesus BB et al, Aging Cell, 2011; Harley CB et al, Rejuvenation Res, 2011) Source: http://genomera.com/studies/aging-telomere-length-and-telomerase-activation-therapy

29. Cellular therapies for wrinkles LaViv (azficel-T) 1 - Fibrocell Science (Exton PA) Approved June 2011 Collagen-producing fibroblasts biopsied from behind the ear and cultured for 90 days Injected into smile line wrinkles Longer-lasting than absorbable fillers VAVELTA, Intercytex (Manchester UK) Human dermal fibroblasts for skin repair and rejuvenation 1 Source: Schmidt C. FDA approves first cell therapy for wrinkle-free visage. Nat Biotechnol. 2011 Aug 5;29(8):674-5. Image credit: http://www.consultingroom.com

30. Facial fat transfer / stem cell facelift Fat removed via liposuction, stem cells harvested from fat, treated, and injected into the face Anti-wrinkle treatment Nasolabial fold and glabellar furrows Stem cells combined with hyaluronic acid (HA) were able to fill in deep folds (Claudio-da-Silva C et al, Rev Col Bras Cir, 2009) Improved skin tone and decreasing lines of expression Image credit: http://www.thebeautyrules.com

31. Aesthetic dermatology treatments Traditional filler injections: botox and hyaluronic acid (HA) Botox alternative Bio Choice No-needle transdermal delivery Skin patches saturated with acetyl hexapeptide (Argireline from Lipotec) Lines smooth with moisture-binding ingredients Local disruption of nerve signals (like botox) Bio-roller microneedle therapy Non-surgical wrinkle treatment Stimulate collagen and elastin production Source: http://www.biojouvance.com Image credit: http://www.biojouvance.com Bio-roller microneedle home therapy system

32. Agenda Top 10 translational anti-aging skin research advances Role of personalized genomics Skin disease profiling Skin wellness profiling Skin care product response Wrinkles: potential causes and translational remedies Other translational anti-aging skin advances Image credit: http://www.hongkiat.com

33. Other areas of translational skin research Regenerative medicine technology translation: military use to aesthetic enhancement Dermal substitutes and next-generation skin grafting Wound-healing and scar reduction Spray-on skin Images credit: http://www.stratatechcorp.com StrataGraft dermal substitute

34. Dermal substitutes/next-generation grafting Apligraf (Organogenesis, Canton MA) Allogeneic cell-based epidermis formed in 20 days Dermagraft (Advanced BioHealing, Westport CT) Cryopreserved dermal substitute derived from human fibroblasts, extracellular matrix, and a bioabsorbable scaffold PermaDerm (Regenicin/Lonza, Little Falls NJ) Autologous tissue-engineered epidermis and dermis in 30 days Cultured fibroblast and kerotinocytes on an absorbable collagen substrate (biomedical polymer) StrataGraft (Stratatech, Madison WI) Epidermal and dermal skin substitute Human keratinocyte progenitor cell line Image credit: http://www.regenicin.com PermaDerm

35. Wound-healing and scar reduction KeraHeal (KeraNetics, Winston-Salem NC) Keratin gel for burn repair; burn dressing and bandages Neodyne (Neodyne Biosciences, Menlo Park CA) Bandage for improved healing and scar reduction Reducing scarring by controlling the mechanical environment (Gurtner GC et al, Ann Surg, 2011) Skin stretching for burn repair to avoid scarring (Verhaegen PD et al, Plast Reconstr Surg, 2011) Neodyne scar prevention 'Band-Aid' Image credit: http://www.internalmedicinenews.com

36. Spray-on skin Skin-cell Gun (Joerg C. Gerlach, Univ Pittsburg) 1 An aerosol system to spray on cultured skin cells ReCell spray-on skin (Avita Medical, Cambridge UK) Autologous cells sprayed in 30-minute on-site procedure Skin-spraying project (James Yoo, Wake Forest Univ) 3-D laser images of would calculate layers of skin to spray 1 Source: http://www.physorg.com/news/2011-02-skin-cell-gun-drastically.html Image credit: http://www.avitamedical.com ReCell Image credit: http://inhabitat.com/skin-cell-spraying-bio-printer-can-heal-burn-victims-in-three-weeks 3-D wound scanner and skin modeling

37. Top 10 anti-aging skin research advances Botox substitutes Skin microbiomics 3-D skin printing Next-generation skin grafting Cellular therapies Genomic disease profiling Genomic product profiling Retinoids and substitutes Spray-on skin Stem cell facelift 2020 2010 2015 Image credit: http://www.dreamstime.com

38. Summary Exciting translational anti-aging skin innovations Personalized genomic profiling Skin disease, wellness, and product response Commercialization of potential anti-wrinkle remedies Topical treatments (retinoids, substitutes, Salicin, CoQ10, laser), cellular therapies, botox/filler substitutes Technology translation: military to aesthetic Dermal substitutes, anti-scarring wound-healing, spray-on skin Image credit: http://www.drbaileyskincare.com

39. Merci! Melanie Swan Founder DIYgenomics +1-650-681-9482 @DIYgenomics www.DIYgenomics.org [email_address] Slides: http://slideshare.net/LaBlogga Creative Commons 3.0 license Collaborators: Lorenzo Albanello Janet Chang Cindy Chen John Furber Eri Gentry Kristina Hathaway Takashi Kido Laura Klemme Lucymarie Mantese Raymond McCauley Louis Nahum Marat Nepomnyashy Ted Odet Roland Parnaso William Reinhardt Greg Smith Aaron Vollrath Lawrence S. Wong Crowd-sourced clinical trials Personal genome apps