Wrinkles and Age Spots

Time marches on, we all get older, and our skin shows the signs of aging. Some people age beautifully with great looking skin; others slather on creams and odd gunk in a futile battle to chase away wrinkles and age spots. Then there is always the Kenny Rogers-style facelift solution…

What is the difference between aging with lots of wrinkles or just a few? Genetics and environmental factors, of course.

What causes skin aging?

Both genetics and environmental factors influence how your skin looks as you age.

Environmental factors that influence skin aging include: [ref]

  • Sun exposure (UV, visible light, and infra-red)
  • Cigarette smoking
  • Air pollution
  • Nutrition
  • Cosmetic products

Wrinkles, loss of elasticity, age spots, loss of tone all contribute to your skin looking older.  A lot of this can be blamed on oxidative stress in the skin. Oxidative stress occurs when there is an imbalance between ROS (reactive oxygen species) and the ability of the cell to counter this with antioxidants. ROS is a byproduct of cellular metabolism (e.g. mitochondria producing energy for the cell) and it is increased by UV radiation. [ref] ROS is also produced during the detoxification of xenobiotics in the endoplasmic reticulum. [ref]

Increased oxidative stress causes an increase in matrix metalloproteinases (MMPs). These are collagen degraders, which decrease the elasticity of the skin. Too much sun exposure results in the breakdown of collagen and elastin and a slower rate of synthesis of collagen. [ref]

Collagen is a protein that forms connective tissue and the extracellular matrix. It is like a structural net or scaffolding that keeps the skin smooth.  Type I collagen is the most abundant in skin, and there is a little type III collagen as well. Sun exposure causes an increase in the expression of MMP1, which causes an increased breakdown of collagen.  [ref]

Genetic variants that cause wrinkles:

Members: Log in to see your data file Not a member? Join now.


The damage to your skin from the sun causes photoaging and age spots. People with lighter skin tones (due in part to the MC1R variants) are more susceptible to photoaging.

IRF4 gene: interferon regulatory factor 4, associated with skin pigmentation, freckles

Check your genetic data for rs12203592 (23andMe v5, AncestryDNA):

  • C/C: most common worldwide
  • C/T: lighter hair and eye color; more photoaging of skin
  • T/T: lighter hair and eye color; more photoaging of skin [ref]

Members: Your genotype for rs12203592 is .

MC1R gene: red hair gene  One study found that carriers of two copies of the risk allele looked on average 2 years older than non-carriers. [ref]

Check your genetic data for rs1805005 (23andMe v4, v5; AncestryDNA):

  • G/G: normal
  • G/T: more photoaging, facial aging
  • T/T: more photoaging, facial aging [ref][ref]

Members: Your genotype for rs1805005 is .

Check your genetic data for rs1805007 (23andMe v4, v5):

  • C/C: normal
  • C/T: more photoaging, facial aging
  • T/T: more photoaging, facial aging[ref][ref]

Members: Your genotype for rs1805007 is .

Check your genetic data for rs1805008 (23andMe v4, v5; AncestryDNA):

  • C/C: normal
  • C/T: more photoaging, facial aging
  • T/T: more photoaging, facial aging[ref][ref]

Members: Your genotype for rs1805008 is .

Check your genetic data for rs1805009 (23andMe v4, v5 as i3002507):

  • G/G: normal
  • C/G: more photoaging, facial aging
  • C/C: more photoaging, facial aging[ref][ref]

Members: Your genotype for i3002507 is .


MMP1 gene: matrix metalloproteinase 1, involved in the breakdown of type I, II, and III collagens

Check your genetic data for rs1799750 (23andMe v4, v5):

  • C/C or I/I: more wrinkles [ref]
  • -/C or D/I: more wrinkles
  • -/- or D/D: fewer wrinkles

Members: Your genotype for rs1799750 is .

STXBP5L gene: 

Check your genetic data for rs322458 (23andMe v5; AncestryDNA):

  • C/C: normal
  • C/T:  normal
  • T/T: decreased photoaging and wrinkles [ref]

Members: Your genotype for rs322458 is .

Check your genetic data for rs470647 (23andMe v4):

  • T/T: normal
  • C/T: normal
  • C/C: decreased photoaging and wrinkles [ref]

Members: Your genotype for rs470647 is .

Sagging Eyelids:

Check your genetic data for rs16927253 (23andMe v4, v5; AncestryDNA):

  • T/T: protective against sagging eyelids[ref]
  • C/T: protective against sagging eyelids
  • C/C: normal

Members: Your genotype for rs16927253 is .



What can you do to fight the genetic hand you’ve been dealt for wrinkles? Read on for a few solutions — or just embrace getting older and be grateful for your years on earth… (Yes, I’m trying to justify a few more wrinkles this year!)

IRF4 variant  – inflammation driven skin aging?

Research shows that IRF4, which is important in the immune response in skin, is also impacted by TNF-alpha, an inflammatory cytokine.[ref]

Decreasing inflammation through targeting TNF-alpha with supplements may help.

Rosmarinic acid (found in rosemary, basil, holy basil, lemon balm, and perilla oil) is a natural TNF-alpha inhibitor.[ref] In addition to adding herbs to your food, holy basil can be found in a tea (called Tulsi tea) or as a supplement.

Curcumin is another natural TNF-alpha inhibitor.[ref] Turmeric is a spice that is a good source of curcumin in the diet; curcumin supplements are also available and may be easier to take on a daily basis

Natural MMP1 inhibitors:

Passionflower and green tea are natural MMP1 inhibitors. [ref] There are lots of options for green tea infused facial lotions.

Retinoic acid also decreases MMP1 expression. [ref] Check out your vitamin A genes to see which kind of vitamin A may work best for you.


There are tons of different products out there that are possibly effective as antioxidants in the skin. So this isn’t an exhaustive list — just hitting the highlights with ones that I think are interesting.

Astaxanthin is a red carotenoid that is found in pink salmon, lobster, shrimp, and algae. It is an antioxidant, with some interesting studies on it.  As far as skin goes, it seems to have some good research showing that it is protective against UV damage. [ref][ref][ref] Astaxanthin is available as a supplement if you can’t afford to eat lobster every day.

Vitamin C is one antioxidant found in skin cells and important in combating oxidative stress.  [ref] Make sure you are getting adequate vitamin C from food sources or through a supplement. Shoot for 90-120mg/day or more. [ref]

Topical vitamin C (5%) has been shown in a clinical trial to diminish purpura, which are the big purple-y blotches that happen in aging skin. [ref] Other studies show that topical vitamin D increases collagen and inhibits MMPs. [ref][ref] There are lots of skin serums available with vitamin C (read the reviews!).

Caffeine has been shown to suppress cellular senescence in skin damaged by UV radiation. [ref] Another way to justify my morning cup (or three) of coffee.

Melatonin acts as an antioxidant and may protect against wrinkle formation. There are some skin creams with melatonin, but they seem to be marketed towards sleep rather than as a skin treatment. [ref][ref] Perhaps a better idea is to block blue light at night and increase your endogenous production of melatonin.

Collagen has been shown to help protect against UVB damage. [ref] Another study showed that a collagen hydrolysate with prolyl-hydroxyproline and hydroxyprolyl-glycine (say that two times, fast) improved facial skin moisture and elasticity. [ref][ref]  Both of those studies were on ingesting collagen peptides rather than putting anything on the skin.  There are tons of collagen supplements on the market these days, or you can get your collagen from bone broth.  I add collagen to my coffee some mornings, but you can put it into pretty much any smoothie or soup.  How much collagen do you need? I have no idea.  It is a good source of amino acids that I don’t get otherwise, so I add it into my coffee whenever I think of it.

Things to Avoid:

Blue light at night has been shown in a recent study to affect skin cells. It was found that exposure to light in the blue wavelengths alters the circadian rhythm of skin cells (independent of the core circadian clock). This caused increased oxidative stress and DNA damage.[ref]  I have no idea what the effect size is on this — is exposure to blue light at night from watching TV going to make us look all wrinkly? or is it such a small change that we wouldn’t notice? Perhaps future research will shed some light (pun intended :) on the subject.