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Circadia by Dr. Pugliese
Michael Q. Pugliese
Skin and Aging Causes, Prevention & Treatment
C I R C A D I A ® 2020
Topics of discussion
What is aging?Todays prominent aging theories and how they are linked to inflammation.
Ingredient technologies designed to address these concerns.
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What is aging?
The gradual deterioration of a mature organism resulting from time-dependent, irreversible changes in structure that are intrinsic to the particular species, and eventually lead to decreased ability to cope with the stresses of the environment, thereby increasing the probability of death.
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What is aging?
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•Genomic instability• Epigenetic alterations•Mitochondrial Dysfunction• Telomere attrition•Glycation• UV and Blue Light Damage• Barrier Disfunction and oxidative stress• Inflammation
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Educating on a “Cellular Level”
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A bit on genes, chromosomes, and DNA
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Genomic Instability
Genomic instability can be viewed as the collective damage to DNA of viable cells from a series of insults including exogenous and endogenous mechanisms
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Epigenetic Alterations
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Depolluphane EpiPlusTriple action to fight urban pollution
Depolluphane EpiPlusTriple action to fight urban pollution
Depolluphane EpiPlusTriple action to fight urban pollution
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Air Pollution – a Complex Toxic MixtureThe contribution of environmental pollution is one of the major areas of concern when it comes to skin aging. In particular, air pollution is directly in contact with our skin and it contributes to skin aging on a daily basis. The main sources of air pollution are industrial combus-tion (diesel exhaust fumes and coal), traffic and con-struction works. Air pollution consists of gases such as ozone and very fine particles that are known as particu-late matter (PM). These particles, which are between 0.1 μm – 10 μm in size, can remain in the atmosphere for weeks and contain toxic compounds such as heavy metals and allergens.
Effects of Pollution on the SkinOur skin is often the first organ to come into contact with air pollution. Particulate matter is especially danger-ous for the skin as it not only sits on the surface but can also penetrate into pores and therefore transport toxic substances into deeper skin layers. In combination with exposure to UV light, these particles cause oxidi-zation reactions within the skin, which lead to the forma-tion of reactive oxygen species (ROS), inflammation and the loss of collagen.
Furthermore, lipid peroxidation caused by ROS leads to skin barrier dysfunction, which creates a vicious cycle as more PM can enter the skin. The result is irritated, uneven skin that will age more rapidly.
Protecting our Skin against PollutionPollution affects our skin on many levels and causes damage, inflammation and accelerated skin aging.
Therefore, a multi-level protection is needed to: • shield the skin from unwanted exposure to pollutants• detoxify the skin by neutralizing dangerous chemicals
that manage to enter the skin• prevent cellular damage caused by free radicals
formed in the skin.
PollutionHarmful for both the environment and skin
Components of the Atmosphere that are Harmful to our Skin
Lipid peroxidation
ROS
DNA damage
Inflammation
Loss of collagen
PM 10 PM 2.5O³ UV CO²
Air Pollution – a Complex Toxic MixtureThe contribution of environmental pollution is one of the major areas of concern when it comes to skin aging. In particular, air pollution is directly in contact with our skin and it contributes to skin aging on a daily basis. The main sources of air pollution are industrial combus-tion (diesel exhaust fumes and coal), traffic and con-struction works. Air pollution consists of gases such as ozone and very fine particles that are known as particu-late matter (PM). These particles, which are between 0.1 μm – 10 μm in size, can remain in the atmosphere for weeks and contain toxic compounds such as heavy metals and allergens.
Effects of Pollution on the SkinOur skin is often the first organ to come into contact with air pollution. Particulate matter is especially danger-ous for the skin as it not only sits on the surface but can also penetrate into pores and therefore transport toxic substances into deeper skin layers. In combination with exposure to UV light, these particles cause oxidi-zation reactions within the skin, which lead to the forma-tion of reactive oxygen species (ROS), inflammation and the loss of collagen.
Furthermore, lipid peroxidation caused by ROS leads to skin barrier dysfunction, which creates a vicious cycle as more PM can enter the skin. The result is irritated, uneven skin that will age more rapidly.
Protecting our Skin against PollutionPollution affects our skin on many levels and causes damage, inflammation and accelerated skin aging.
Therefore, a multi-level protection is needed to: • shield the skin from unwanted exposure to pollutants• detoxify the skin by neutralizing dangerous chemicals
that manage to enter the skin• prevent cellular damage caused by free radicals
formed in the skin.
PollutionHarmful for both the environment and skin
Components of the Atmosphere that are Harmful to our Skin
Lipid peroxidation
ROS
DNA damage
Inflammation
Loss of collagen
PM 10 PM 2.5O³ UV CO²
Air Pollution – a Complex Toxic MixtureThe contribution of environmental pollution is one of the major areas of concern when it comes to skin aging. In particular, air pollution is directly in contact with our skin and it contributes to skin aging on a daily basis. The main sources of air pollution are industrial combus-tion (diesel exhaust fumes and coal), traffic and con-struction works. Air pollution consists of gases such as ozone and very fine particles that are known as particu-late matter (PM). These particles, which are between 0.1 μm – 10 μm in size, can remain in the atmosphere for weeks and contain toxic compounds such as heavy metals and allergens.
Effects of Pollution on the SkinOur skin is often the first organ to come into contact with air pollution. Particulate matter is especially danger-ous for the skin as it not only sits on the surface but can also penetrate into pores and therefore transport toxic substances into deeper skin layers. In combination with exposure to UV light, these particles cause oxidi-zation reactions within the skin, which lead to the forma-tion of reactive oxygen species (ROS), inflammation and the loss of collagen.
Furthermore, lipid peroxidation caused by ROS leads to skin barrier dysfunction, which creates a vicious cycle as more PM can enter the skin. The result is irritated, uneven skin that will age more rapidly.
Protecting our Skin against PollutionPollution affects our skin on many levels and causes damage, inflammation and accelerated skin aging.
Therefore, a multi-level protection is needed to: • shield the skin from unwanted exposure to pollutants• detoxify the skin by neutralizing dangerous chemicals
that manage to enter the skin• prevent cellular damage caused by free radicals
formed in the skin.
PollutionHarmful for both the environment and skin
Components of the Atmosphere that are Harmful to our Skin
Lipid peroxidation
ROS
DNA damage
Inflammation
Loss of collagen
PM 10 PM 2.5O³ UV CO²
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C I R C A D I A ® 2020
Air Pollution – a Complex Toxic MixtureThe contribution of environmental pollution is one of the major areas of concern when it comes to skin aging. In particular, air pollution is directly in contact with our skin and it contributes to skin aging on a daily basis. The main sources of air pollution are industrial combus-tion (diesel exhaust fumes and coal), traffic and con-struction works. Air pollution consists of gases such as ozone and very fine particles that are known as particu-late matter (PM). These particles, which are between 0.1 μm – 10 μm in size, can remain in the atmosphere for weeks and contain toxic compounds such as heavy metals and allergens.
Effects of Pollution on the SkinOur skin is often the first organ to come into contact with air pollution. Particulate matter is especially danger-ous for the skin as it not only sits on the surface but can also penetrate into pores and therefore transport toxic substances into deeper skin layers. In combination with exposure to UV light, these particles cause oxidi-zation reactions within the skin, which lead to the forma-tion of reactive oxygen species (ROS), inflammation and the loss of collagen.
Furthermore, lipid peroxidation caused by ROS leads to skin barrier dysfunction, which creates a vicious cycle as more PM can enter the skin. The result is irritated, uneven skin that will age more rapidly.
Protecting our Skin against PollutionPollution affects our skin on many levels and causes damage, inflammation and accelerated skin aging.
Therefore, a multi-level protection is needed to: • shield the skin from unwanted exposure to pollutants• detoxify the skin by neutralizing dangerous chemicals
that manage to enter the skin• prevent cellular damage caused by free radicals
formed in the skin.
PollutionHarmful for both the environment and skin
Components of the Atmosphere that are Harmful to our Skin
Lipid peroxidation
ROS
DNA damage
Inflammation
Loss of collagen
PM 10 PM 2.5O³ UV CO²
Air Pollution – a Complex Toxic MixtureThe contribution of environmental pollution is one of the major areas of concern when it comes to skin aging. In particular, air pollution is directly in contact with our skin and it contributes to skin aging on a daily basis. The main sources of air pollution are industrial combus-tion (diesel exhaust fumes and coal), traffic and con-struction works. Air pollution consists of gases such as ozone and very fine particles that are known as particu-late matter (PM). These particles, which are between 0.1 μm – 10 μm in size, can remain in the atmosphere for weeks and contain toxic compounds such as heavy metals and allergens.
Effects of Pollution on the SkinOur skin is often the first organ to come into contact with air pollution. Particulate matter is especially danger-ous for the skin as it not only sits on the surface but can also penetrate into pores and therefore transport toxic substances into deeper skin layers. In combination with exposure to UV light, these particles cause oxidi-zation reactions within the skin, which lead to the forma-tion of reactive oxygen species (ROS), inflammation and the loss of collagen.
Furthermore, lipid peroxidation caused by ROS leads to skin barrier dysfunction, which creates a vicious cycle as more PM can enter the skin. The result is irritated, uneven skin that will age more rapidly.
Protecting our Skin against PollutionPollution affects our skin on many levels and causes damage, inflammation and accelerated skin aging.
Therefore, a multi-level protection is needed to: • shield the skin from unwanted exposure to pollutants• detoxify the skin by neutralizing dangerous chemicals
that manage to enter the skin• prevent cellular damage caused by free radicals
formed in the skin.
PollutionHarmful for both the environment and skin
Components of the Atmosphere that are Harmful to our Skin
Lipid peroxidation
ROS
DNA damage
Inflammation
Loss of collagen
PM 10 PM 2.5O³ UV CO²
Air Pollution – a Complex Toxic MixtureThe contribution of environmental pollution is one of the major areas of concern when it comes to skin aging. In particular, air pollution is directly in contact with our skin and it contributes to skin aging on a daily basis. The main sources of air pollution are industrial combus-tion (diesel exhaust fumes and coal), traffic and con-struction works. Air pollution consists of gases such as ozone and very fine particles that are known as particu-late matter (PM). These particles, which are between 0.1 μm – 10 μm in size, can remain in the atmosphere for weeks and contain toxic compounds such as heavy metals and allergens.
Effects of Pollution on the SkinOur skin is often the first organ to come into contact with air pollution. Particulate matter is especially danger-ous for the skin as it not only sits on the surface but can also penetrate into pores and therefore transport toxic substances into deeper skin layers. In combination with exposure to UV light, these particles cause oxidi-zation reactions within the skin, which lead to the forma-tion of reactive oxygen species (ROS), inflammation and the loss of collagen.
Furthermore, lipid peroxidation caused by ROS leads to skin barrier dysfunction, which creates a vicious cycle as more PM can enter the skin. The result is irritated, uneven skin that will age more rapidly.
Protecting our Skin against PollutionPollution affects our skin on many levels and causes damage, inflammation and accelerated skin aging.
Therefore, a multi-level protection is needed to: • shield the skin from unwanted exposure to pollutants• detoxify the skin by neutralizing dangerous chemicals
that manage to enter the skin• prevent cellular damage caused by free radicals
formed in the skin.
PollutionHarmful for both the environment and skin
Components of the Atmosphere that are Harmful to our Skin
Lipid peroxidation
ROS
DNA damage
Inflammation
Loss of collagen
PM 10 PM 2.5O³ UV CO²
C I R C A D I A ® 2020
EpigeneticsLong-term effects of pollution
What Is Epigenetics?Recent research has shown that the short-term effects of oxidative stress are not the only danger: continuous exposure to air pollution causes epigenetic changes in our cells that can persist in the long-term, even after the harmful exposure is no longer there.
Epigenetics can be explained as being a structure above the genome (epigenetics = “on top of genetics”) that regulates gene expression without changing the DNA code. DNA, which makes each individual unique, holds the instructions for building all of the parts of the body and it is wrapped around proteins that are called histones.
The epigenetic regulation works by covering DNA and histones with chemical tags. These marks, which for example include histone methylation, acetylation and phosphorylation, make some genes either readable or not readable without changing the DNA sequence.
Epigenetics and PollutionIn the past few years, an effort has been made in order to elucidate the effect of pollution on epigenetics. For example, steel workers who inhale higher amounts of PM and heavy metals showed a distinct increase in histone H3 lysine 4 dimethylation (H3K4me2) in their blood 1. For the first time, we have been able to demonstrate a distinct histone modification pattern for histone H3 in skin cells that are exposed to pollution.
Therefore, a multi-level protection is needed; not only to shield the skin from unwanted exposure to pollutants and detoxify the skin by neutralizing dangerous chemicals that manage to enter the skin, but also to prevent long-term epigenetic changes that are caused by pollution.
1 Cantone et al., Environ Health Perspect. 2011
Epigenetic Histone Modifications
Methylation Phosphorylation Acetylation
Chromosome
DNA strand
Histone tail with chemical tags
Histone
EpigeneticsLong-term effects of pollution
What Is Epigenetics?Recent research has shown that the short-term effects of oxidative stress are not the only danger: continuous exposure to air pollution causes epigenetic changes in our cells that can persist in the long-term, even after the harmful exposure is no longer there.
Epigenetics can be explained as being a structure above the genome (epigenetics = “on top of genetics”) that regulates gene expression without changing the DNA code. DNA, which makes each individual unique, holds the instructions for building all of the parts of the body and it is wrapped around proteins that are called histones.
The epigenetic regulation works by covering DNA and histones with chemical tags. These marks, which for example include histone methylation, acetylation and phosphorylation, make some genes either readable or not readable without changing the DNA sequence.
Epigenetics and PollutionIn the past few years, an effort has been made in order to elucidate the effect of pollution on epigenetics. For example, steel workers who inhale higher amounts of PM and heavy metals showed a distinct increase in histone H3 lysine 4 dimethylation (H3K4me2) in their blood 1. For the first time, we have been able to demonstrate a distinct histone modification pattern for histone H3 in skin cells that are exposed to pollution.
Therefore, a multi-level protection is needed; not only to shield the skin from unwanted exposure to pollutants and detoxify the skin by neutralizing dangerous chemicals that manage to enter the skin, but also to prevent long-term epigenetic changes that are caused by pollution.
1 Cantone et al., Environ Health Perspect. 2011
Epigenetic Histone Modifications
Methylation Phosphorylation Acetylation
Chromosome
DNA strand
Histone tail with chemical tags
Histone
C I R C A D I A ® 2020
EpigeneticsLong-term effects of pollution
What Is Epigenetics?Recent research has shown that the short-term effects of oxidative stress are not the only danger: continuous exposure to air pollution causes epigenetic changes in our cells that can persist in the long-term, even after the harmful exposure is no longer there.
Epigenetics can be explained as being a structure above the genome (epigenetics = “on top of genetics”) that regulates gene expression without changing the DNA code. DNA, which makes each individual unique, holds the instructions for building all of the parts of the body and it is wrapped around proteins that are called histones.
The epigenetic regulation works by covering DNA and histones with chemical tags. These marks, which for example include histone methylation, acetylation and phosphorylation, make some genes either readable or not readable without changing the DNA sequence.
Epigenetics and PollutionIn the past few years, an effort has been made in order to elucidate the effect of pollution on epigenetics. For example, steel workers who inhale higher amounts of PM and heavy metals showed a distinct increase in histone H3 lysine 4 dimethylation (H3K4me2) in their blood 1. For the first time, we have been able to demonstrate a distinct histone modification pattern for histone H3 in skin cells that are exposed to pollution.
Therefore, a multi-level protection is needed; not only to shield the skin from unwanted exposure to pollutants and detoxify the skin by neutralizing dangerous chemicals that manage to enter the skin, but also to prevent long-term epigenetic changes that are caused by pollution.
1 Cantone et al., Environ Health Perspect. 2011
Epigenetic Histone Modifications
Methylation Phosphorylation Acetylation
Chromosome
DNA strand
Histone tail with chemical tags
Histone
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Revita-Cyte Complex
Key Ingredients:Euk-134- Mitochondrial form of superoxide dismutaseMicroalgae extract (Pepha-ctive)- protects and stimulates mitochondria by increasing ATP levels; improves skin radiance Oat Beta Glucan- immune stimulantExo-T- Vitamin A alternative, increases cell turnover, stimulates desquamation, exfoliationMatryxyl sinth 6- evens out skin relief and smoothes wrinklesChronocyclin – enhances vitamin D expression by mimicking sun exposure
Skin Type Indications: Aging, damaged, sensitive to Vitamin A
Benefits: • Wrinkle reduction • Increase cell turnover • Peptides, stem cells, botanicals & vitamins • Increases ATP Energy
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“Chronic (daily), invisible (subclinical)
inflammation sustained over a lifetime is the underlying
cause of aging.”- Peter Pugliese, M.D. - 1989
This means aging can be slowed & some forms may even be prevented.
What is the bottom line of aging?
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DNA damage from UV radiation
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Mitochondrial DysfunctionMany researchers that support the free radical theory of aging believe that damage to the cell accumulates from ROS generated by the mitochondria.
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Krebs Cycle
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A bit on ROS (reactive oxygen species)
Singlet Oxygen
Superoxide
Hydrogen peroxide
Hydroxyl Radical
Begins ROS CascadeExcites other moleculesDiffuses easily Leads to Aging & Disease Causing inflammation Oxidizes Barrier Lipids & Cell MembranesPromotes InflammationCyto cell toxicCreates Hydroxyl RadicalMost Dangerous & Damaging of All ROS, Attacks & Mutates DNA
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The Barrier
Environmental insults can greatly damage the barrier and its built in mechanisms for repair, leading to more inflammation, increased sensitivity and greater production of free radicals.
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So What is Glycation?
Glycation is the non-enzymatic joining of a sugar compound with a protein, lipid, or amino acids impairing their function or making them nonfunctional. Everything we eat has a certain amount of advance glycation end units or short AGE.
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The Chemistry of Glycation
The Maillard Reaction
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Making it simple….
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DNADNA
Signal Transmitted
Acts on
DNA
Multiple products
Receptor
Ligand
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A Closer Look
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Counter A.G.E. (advanced glycation end units)
Key Ingredients:DermalRx LuShield- Detoxifies skin from glycating agentsdGlyage- anti-A.G.E. formationVilastene- reduces A.G.E.sAlpaflor Plantago AO(Plantain Stem Cell)- enhances collagen production,L-carnosine- anti-glycation Phito-Sirt- prevents glycation Derm SRC PF- increases collagen, elastin and hyaluronic acid synthesis
Skin Type Indications: Glycated, aging, damaged
Benefits: • Anti-glycation• Antioxidant• Detoxify
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Glyco-Guard
Key Ingredients:Benfotiamine- controls the formation of A.G.E.sSurviCode - promotes cellular longevity, cell communication, and cell defenseDermalRx LuShield- Detoxifies skin from glycating agents and oxidantsMatryxyl sinth 6- evens out skin relief and smoothes wrinklesDecarboxycarnosine (Alistin)- anti-glycation and antioxidantAlpaflor ABI Complex AO- DNA protective, supports wound healing, and re-epithelialization, contains antioxidants.
Skin Type Indications: Glycated, aging, damaged
Benefits: • Anti-glycation• Antioxidant• Wrinkle reduction
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Stem Cell Exhaustion
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Stem Cell Exhaustion
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Nighttime Repair
Key Ingredients:Retinyl acetate- .3%; regenerative, increases cell turnoverMatrxyl Syth 6- Reduces wrinkle depth, increases firmness Ergothionine (Thiotaine)- antioxidant that helps to regenerate vitamin CPhytosirt- Complex of Mexican bamboo,prevents glycation Tetrahexyldecyl ascorbate-Brightening, collagen support, protection Tocopherol acetate- very powerful fat-soluble antioxidant
Skin Type Indications: Aging, damaged, glycated
Benefits: • Increase cell turnover• Wrinkle reduction• Antioxidant• Increase firmness
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Nighttime Repair Plus
Key Ingredients:Retinyl acetate- .5%; regenerative, increases cell turnoverMatrxyl Syth 6- Reduces wrinkle depth, increases firmness Ergothionine (Thiotaine)- antioxidant, regenerated vitamin CPhytosirt- Complex of Mexican bamboo,prevents glycation Tetrahexyldecyl ascorbate-Brightening, collagen support, protection Tocopherol acetate- very powerful fat-soluble antioxidantROXISOMES - Repairs DNA damage
Skin Type Indications: Advanced Aging, damaged, glycatedBenefits: • Increase cell turnover• Wrinkle reduction• Antioxidant• Increase firmness
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Vitamin A Boosting Cream
Key Ingredients:Retinyl acetate- 1.0%; regenerative, increases cell turnover
Skin Type Indications: Advanced Aging, damaged, vitamin A Booster
Benefits: • Increase cell turnover• Wrinkle reduction• Increase firmness • Used to boost Vitamin A Regimens
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Vitamin A Gel
Key Ingredients:Retinol - 1.0%; regenerative, increases cell turnover
Skin Type Indications: Aging skin, or skin requiring rejuvenation
Benefits: • Increase cell turnover• Wrinkle reduction• Increase firmness • Gel base
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Telomere attrition Telomeres are the caps at the end of each strand of DNA that protect our chromosomes, like the plastic tips at the end of shoelaces.
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Progeria
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Progeroid Syndromes
Xeroderma Pigmentosum
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Cyto-Comm
Key Ingredients:DermalRx LuShield- Anti-GlycationDermCom- boosts collagen and elastin productionProgeline- reduces signs of aging including sagging and wrinklesAminopropyl ascorbyl phosphate (Vita C)- stabilized form of Vitamin C which stabilizes E ,antioxidantGlycine, Lysine, Proline, Valine, Alanine- Amino acids to promote collagen formation and signaling
Skin Type Indications: All Skin Types, Aging, loss of elasticity and collagen
Benefits: • Enhance cell to cell communication• Amino Acids • HA Base• Anti-Glycation
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The suns energy comes to us in the form of rays that are essentially particles called photons that move in waves
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A bit on photochemistry
Suns rays are unique in that they are recognized as both waves and particles.
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Anatomy of a wave
• UVA• 400 – 315 nm• UVB• 315 – 280 nm• UVC• 280 – 100 nm
It should be noted that UVB is at least 1000x stronger than UVA. This is what is meant by broad spectrum.
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DNA damage from UV radiation
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So What happens when this energy reaches the skin?
UVB has a short wavelength and therefore a higher energy but primarily affects epidermal cells. When UVB hits the skin, because the energy is so great, it is capable of creating crosslinking in the DNA of epidermal cells. If the body cannot correct this abnormal change it can create a mutation that leads to cancerous cell growth.
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Sun induced carcinoma
• Basal cell Carcinoma
• Squamous cell carcinoma
• Melanoma
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So What happens when this energy reaches the skin? UVA has a longer wavelength and penetrates deeper into the dermis, however has significantly less energy than UVB. When UVA hits the skin it creates crosslinking of dermal proteins collagen and elastin. This leads to severe stiffening making them non-functional.TIMPs are also found to be greatly degraded by UVA.
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Free radical stress and photo damage from UVA exposure
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Light Day Sunscreen Broad Spectrum SPF -37
Key Ingredients:Avobenzone, Octinoxate, Octocrylene - absorbs UVA & UVB rays SolaStay- award winning photo stabalizerPhytoCellTech Solar Vitis (Grape Seed Stem Cell)- regenerate, hydrate and protect against UV Damage/Oxidative damageLipochroman 6- protects cells from internal free radical damagePreventhilia- peptide that prevents damage caused by UV radiation to the DNA and proteins.
Skin Type Indications: All Skin Types
Benefits: • UVA/UVB Protection• Fights free radical damage • Hydrating • Anti-aging day cream with sun protection• Environmental protection
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Wrinkle formation
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Myo-Cyte Plus
Key Ingredients:MatrixylTM - Helps stimulate collagen synthesis and elastin. Matrixyl 3000TM - Helps repair damaged tissuesSnap-8 – Reduces depth of wrinkles Inyline – Reduces depth of wrinkles L-Carnosine- Essential amino acid that is anti-glycation propertiesPassion Flower Extract- Contains three powerful muscle relaxants that are effective in smoothing wrinkled skin
Skin Type Indications: Aging, damaged
Benefits: • Powerful wrinkle reduction • Anti-glycation• Minimize muscle contraction • SPOT TREAT
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