The Science of Looking Younger, Longer

Menopause and Hormone Replacement Therapy

• Menopause affects women’s reproductive system earlier than other organs show damage from aging
• Menopause symptoms: mood swings, vaginal dryness, loss of sex drive, migraines, hot flashes, increased susceptibility to heart disease
• Menopausal hormone therapy can offer symptomatic relief 
  • Traditionally estrogen replacement, but increasingly exploring other hormones
  • Dual use of estrogen and progesterone in the right combination, ratio, and timing is important
  • Women should measure baseline levels of estrogen and progesterone during their 30s and 40s to help physicians match those levels during menopause
• Monitoring health data is crucial for both men and women 
  • Measure levels of sex hormone-​​binding globulin (SHPG) as well
• Long-​​term hormone replacement therapy may protect against heart disease and bone loss 
  • Consult with a physician, especially if there’s a history of breast cancer

Epidermal Thinning

• Accelerated during and after menopause
• Affects the skin’s appearance as it ages

Monitoring Blood Glucose Levels

Skin Health and Aging

• Largest organ in the human body, 1/​​6 of total body weight
• Barrier to the world, health of skin important for overall health
• Epidermal thinning a problem for aging individuals, especially women during menopause
• Thin skin can lead to easier bruising, tearing, and infection

Foot Ulcers

• Affect about 13% of the US population
• Can arise from tripping or stepping on sharp objects
• Difficult to heal, can lead to amputation and infection
• Importance of maintaining skin health and thickness

Appearance and Aging

• 2012 study: elderly people rated on appearance, health, attractiveness, and facial symmetry
• Those rated as older-​​looking more likely to die within seven years
• Suggests a correlation between appearance and biological age
• DNA methylation clocks can help measure biological age in specific tissues, such as skin
  Skin Aging and Sun Damage
• Skin ages faster due to exposure to elements like UV light 
  • UV light creates DNA damage that accelerates epigenetic changes leading to aging
• A third of Australians suffer from some form of skin cancer due to sun exposure 
  • Beaches in Australia now provide free sunscreen to reduce healthcare costs

Senescent Cells and Skin Aging

• Skin is full of senescent cells, which are zombie-​​like cells that stop dividing and producing 
  • They secrete inflammatory factors and mitogens that stimulate cancer
• Deleting senescent cells can lead to rejuvenation of the body, including skin
• Lowering the overall burden of senescent cells is beneficial for overall health

UV Light Damage and DNA

• Sunlight causes two DNA letters (T’s) to link chemically, creating thymine dimers 
  • This prevents DNA from being read and copied properly
• The act of repairing DNA damage is the problem, leading to cell losing its identity

Peptides and Skin Rejuvenation

• Peptides can potentially reverse skin aging by targeting senescent cells 
  • One Skin is a product containing a peptide that shows efficacy in human clinical trials
• Collagen is an important component of younger skin, making it more flexible and thicker 
  • Collagen production decreases as we age
• Retinol and vitamin C are currently more effective in protecting and rejuvenating skin 
  • Retinoids boost collagen production and stimulate cell growth
    Retinol and Skin Care
• Retinol products can cause dry skin, requiring moisturization
• Retinols inhibit MMPs (metalloproteases) that break down the skin
• Retinols promote keratinocyte growth, which produces keratin (important for skin, hair, and nails)

Nail Growth and Aging

• Nail growth rate can indicate biological age
• Nail growth decreases about 0.5% per year
• Faster nail growth may indicate slower aging

Autophagy and Retinol

• Retinol can engage in autophagy (recycling of old proteins in the cell)
• Chaperone-​​mediated autophagy (CMA) can extend lifespan in animals
• Retinol may stimulate body growth but could be at the expense of long-​​term skin health

Antioxidants in Skin Creams

• Resveratrol is a weak antioxidant but may activate sirtuin activity, which has various benefits
• NAD-​​boosting molecules like nicotinamide or nicotinic acid can be found in cosmetics and may have beneficial effects on the skin

Hyaluronic Acid (HA) in Skin Care

• HA is important for skin plumpness and flexibility
• Found in abundance in long-​​lived organisms, potentially protecting against cancer
• Topical HA works well as a moisturizer, but injectable HA may be more effective for improving volume loss and laxity of the skin

Botox and Anti-Aging

• Botox is a toxin from the bacterium Clostridium botulinum
• Inhibits neurotransmission, relaxing muscles and reducing wrinkles
• Effective for wrinkle reduction but requires repeated injections every 6–9 months
  Cosmetic Treatments and Longevity
• Numbing nerves for cosmetic purposes 
  • Not medical, but can improve social life and overall well-being
• Skin peels
  • Make skin look nice, but no real benefit to skin age
• Micro needling
  • May induce minor stress, hormesis, and repair factors
  • Long-​​term benefits on skin age not proven

Lifestyle Factors Affecting Skin and Hair

• Sun damage
  • Staying out of the sun is important for skin health
• Smoking
  • Accelerates aging in the body and shows up on the skin
• Alcohol
  • Research shows it’s bad for skin health
• Diet
  • Processed foods, fats, and chemicals can affect aging and skin health
  • Good diet can improve skin and hair health

Hair Loss and Graying

• Over 600 genes involved in hair loss 
  • 20 found on the X chromosome (from mother)
  • Strong genetic component
• Hair loss treatments 
  • Topical treatments (e.g., Minoxidil/​​Rogaine)
    • Stimulates nitric oxide production, slows hair loss
  • Retinol cream
    • Can reduce wrinkles and slow hair loss
  • Pills (e.g., Propecia/​​Finasteride)
    • Inhibits dihydrotestosterone (DHT), slows hair loss

Optimal DHT Levels for Longevity

• Study of 3,690 men found optimal DHT levels for longevity 
  • Relatively low, but within middle range (9.8 to 15.8 nanomoles per liter)
• Eunuchs (men without testicles) 
  • Live 14 to 19 years longer than regular men
  • Not a recommended longevity strategy
    Eunuchs and Longevity
• Eunuchs tend to live longer than the general population 
  • 3 out of 81 eunuchs studied became centenarians
  • 130 times greater chance of reaching 100 than the general population
• Excess testosterone and growth hormone may promote aging

Inhibited Testosterone and Side Effects

• Lowered sex drive
• Mood swings
• Depression
• Breast tenderness

Low Laser Light Therapy (LLLT)

• FDA-​​approved treatment for hair loss
• Red laser light combs and caps
• Clinical trials show slowed hair loss and regrowth in some people
• Unclear how it works, but may involve nitric oxide and mitochondrial function

Platelet Rich Plasma (PRP) Injections

• Used for sports injuries and hair loss
• Blood is taken, spun to separate platelets, and injected into the scalp
• Contains exosomes, hormones, peptides, and possibly V cells
• Unclear which components promote hair growth

Hair Growth in Unwanted Places

• Possibly due to changes in the DNA structure (epigenome) over time
• Ancient genetic code may become readable by cells as we age

Graying Hair and Stress

• Stress can accelerate graying hair
• Recent research shows graying hair can be reversible
• Melanocytes, which produce pigment, may become dysfunctional before dying
• Epigenetic effect: gray hair may be reversible in early stages

Potential Treatments for Graying Hair

• Adversity mimetics to reset the epigenome
• Combination of compounds, including cyclosporin A, minoxidil, and a pigment-​​promoting drug
  Tacrolimus and Hair Repigmentation
• Tacrolimus: similar molecule to rapamycin (Psorolimus)
  • Extends lifespan, inhibits mTOR protein complex, responds to fasting
  • Immunosuppressant, signals adversity to cells
• Cyclosporine A: immunosuppressant, prevents organ rejection 
  • Rejuvenates mitochondria, preserves mitochondrial permeability transition pore (mPTP)
• Minoxidil: improves blood flow
• Combination of cyclosporine A, minoxidil, and pigment-​​promoting drug (analog of rapamycin) could restore hair color 
  • Not yet ready for human use, but potential for future products
• Addressing aging pathways can have downstream effects on individual problems related to aging

Rejuvenating Effects in Other Organs

• Lessons learned from reversing aging in skin and hair can be applied to other organs 
  • Rapamycin, cyclosporine, and minoxidil could potentially be used in low doses for rejuvenating effects
• Future possibility of taking pills to not only get younger but also regrow and darken hair

Big Takeaway

• On the verge of reversing aging internally and externally 
  • Injectable, edible, and smearable methods for delivering molecules to slow down and reverse aging
• Importance of exercise, diet, sleep, and stress management for overall health and appearance
• Keeping oneself looking good through healthy habits can lead to a longer life