The Science of Looking Younger, Longer | Lifespan with Dr. David Sinclair #6

Launching Episode Six: Combating Cosmetic Aging & Improving Skin, Nails & Hair (00:00:00)

• Lifespan Podcast focuses on the science of aging with Dr. David Sinclair discussing how to slow or reverse aging.
• Joined by co-presenter Matthew LaPlante, episode six touches on cosmetic aging, distinguishing between purely aesthetic treatments and those impacting biological aging.
• Aesthetic improvements are valued for social and emotional benefits, but emphasis is on technologies that fight aging at a biological level, including adversity and abundance mimetics.
• Discussion includes methods for maintaining youthful appearance of hair, skin, and nails, and potentially reversing aging aspects.

Estrogen, Progesterone, and Menopause (00:02:54)

• Conversation shifts to women's health, particularly menopause and its early onset impact on aging, neglecting it in a previous episode.
• Hormone Replacement Therapy (HRT) can assist women through menopause by maintaining proper hormone levels to protect against aging.
• Concerns about menopause's harsh symptoms include mood swings, migraines, hot flashes, and increased risk of heart disease.
• Advice on monitoring hormone levels to customize HRT and tracking health indicators like Sex Hormone Binding Globulin (SHBG) to increase therapy effectiveness.
• Correct ratios and timing of estrogen and progesterone are crucial; prolonged HRT can prevent issues like heart disease and bone loss, though risks exist for breast cancer patients.
• Menopause also causes epidermal thinning, which ties into the theme of cosmetic aging and overall skin health.

The Pinch Test, Epidermal Thinning, and Foot Ulcers (00:12:57)

• Skin is the largest organ, 1/6 of body weight, and vital for overall health.
• The skin pinch test is a quick assessment of skin's aging; younger skin snaps back quickly, while older skin takes longer.
• Skin thins with age, leading to increased risks like bruising, tearing, and poor wound healing.
• Epidermal thinning is particularly problematic post-menopause and in the elderly.
• 13% of the US population suffers from foot ulcers, which are severe in elderly due to non-healing wounds.
• Ulcers can worsen with conditions like diabetes leading to amputations and increased mortality.

Skin and Biological Aging (00:18:29)

• Aging skin is more than an aesthetic issue; it is related to overall health and lifespan.
• A study showed older-looking individuals were more likely to die within seven years than younger-looking people of the same age.
• Families with centenarians often look younger than their chronological age, suggesting a correlation between looks and biological age.
• While initial studies showed no correlation between biological clocks and perceived age, later studies using skin-specific clocks found a better correspondence.
• Skin can age faster than other tissues due to environmental exposure, such as UV light which can cause DNA damage and accelerate aging.
• Australians have high skin cancer rates due to UV exposure, prompting public health measures like complimentary sunscreen at beaches.
• Damaging effects of the sun are now better understood, with suggestions that some damage to the skin may be reversible.

Cellular Senescence, Ultraviolet Light, and Skin Aging (00:23:19)

• Skin aging involves accumulation of senescent cells which stop dividing and secrete harmful inflammatory factors.
• Senolytic drugs, like ABT-263 (Navitoclax) and rapamycin, can kill senescent cells and rejuvenate skin.
• A study demonstrated that treating skin biopsies with senolytics thickened the skin and reversed its biological age, as measured by a specialized skin DNA methylation clock.
• Senescent cells contribute to overall aging, with most senescent cells in the skin due to UV damage.
• Protecting skin from UV light, using sunscreen, and potentially employing senolytics can decrease the load of senescent cells.
• UV light causes DNA damage by fusing adjacent thymine bases in DNA, impeding DNA replication and cell function.
• Repairing DNA damage from UV exposure disrupts cellular protein organization, leading to cell identity loss.

Collagen, Keratin, and Skin Health (00:28:15)

• Currently, senolytic drugs like rapamycin and ABT-263 are not available for topical use on skin.
• Peptides from a skin study were found to have anti-aging effects when applied topically, with one peptide showing promise in a product called OneSkin.
• Collagen production decreases with age and is a target for many beauty products to enhance skin health.
• The effectiveness of ingesting collagen supplements and their ability to reach the bloodstream intact is uncertain, but they are considered safe.
• Retinoids are proven to boost collagen production, reduce wrinkles, and promote the growth of skin layers and fibroblasts while reducing pigmentation.
• Use of retinoids must be balanced to avoid dryness and sensitivity to sunlight.
• Retinoids activate certain genes for cell growth and inhibit enzymes that degrade skin proteins.
• Keratinocytes, which produce keratin, another key protein for skin, hair, and nails, can be stimulated by retinoids.

A Quick Aside about Nails (00:33:38)

• Nail growth rate is an indicator of biological aging, decreasing about half a percent per year.
• Historical data, such as a long-term study by an individual named Mr. Bean, support that nail growth rates correlate with the aging process.

Autophagy and Retinoids (00:34:45)

• Biting nails can be jestingly associated with autophagy, a process beneficial to lifespan.
• Autophagy involves recycling old proteins in the cell, and can be influenced by retinoic acids.
• Different levels of autophagy occur, from shallow (skipping meals) to deeper cleansing (extended fasting).
• A protein called LAMP2A, controlled by retinoic acids, regulates deeper chaperone-mediated autophagy.
• Enhancing chaperone-mediated autophagy in mice significantly increased their lifespan.
• Retinoids, despite having benefits, might negatively impact long-term skin health by inhibiting this autophagy mechanism.
• It's suggested to use retinols intermittently, possibly avoiding use when fasting.

Resveratrol, NAD Boosters, and Hyaluronic Acid (00:36:57)

• Literature suggests that most antioxidants do not have a significant impact on longevity.
• Resveratrol, while an antioxidant, likely benefits the skin by activating body defenses and sirtuin activity, not through its antioxidant properties.
• Topical creams with resveratrol and NAD-boosting molecules, like nicotinamide, are beneficial for skin health.
• Ongoing research is focused on boosting NAD directly in the skin.
• Hyaluronic acid (HA) is acclaimed for its skin and body-wide benefits, including cancer resistance in studies with animals like naked mole rats.
• Injectable HA can be effective for skin volume loss and laxity.
• Smaller HA oligomers in creams may penetrate the skin better, and resveratrol can enhance HA synthesis.

Botox, Skin Peels, and Microneedling (00:41:44)

• Botox is a popular cosmetic treatment for wrinkles that works by inhibiting neurotransmission to muscles.
• The effects of Botox are cosmetic, with no known anti-aging implications at the cellular level beyond appearance.
• Skin peels mainly provide a superficial benefit, rather than anti-aging effects.
• Microneedling might trigger hormetic effects that potentially benefit skin aging, though confirmation is needed.

No Duh Stuff: Sun Damage, Smoking, Alcohol, and Bad Food (00:43:28)

• Avoiding sun damage, smoking, and the consumption of alcohol is critical for maintaining skin health.
• Alcohol consumption was recently associated with negative skin effects.
• Poor diet, especially one high in processed foods, fats, and chemicals, accelerates aging visibly in skin and hair.

Hair Loss and Hair Graying (00:45:42)

• Hair loss has over 600 genes involved, with only about 20 on the X chromosome, accounting for roughly 11% of male pattern baldness.
• For females, hair loss genetics are split 50/50 between both parents since the X chromosome is involved.
• Hair loss is strongly genetically determined, and while it can be slowed, it's not a major health concern and in some professions, long hair can be hazardous.
• Evolutionarily, hair loss and graying signified dominance and wisdom, as seen in the silverback gorilla's societal structure.
• Hair loss at a cellular level involves malfunctioning hair follicle stem cells getting expelled and follicle shrinkage due to dihydrotestosterone, leading to thinner hair.

Topical Treatments, Pills, and Dihydrotestosterone (00:49:45)

• Minoxidil (Rogaine), a treatment for hair loss, was initially a blood pressure medication and stimulates nitric oxide production, promoting hair growth.
• Tretinoin (Retin-A) also promotes hair regrowth, especially when combined with minoxidil.
• The pill Propecia (finasteride) inhibits dihydrotestosterone (DHT), which is linked to hair thinning; optimal DHT levels correlate with longevity.
• Studies have shown eunuchs live significantly longer than average men, suggesting lower levels of testosterone might increase lifespan.
• Propecia can reduce hair loss effectively, but it can also have side effects like mood swings, decreased sex drive, and breast tenderness, so monitoring and doctor guidance are essential.

Frickin Laser Beams: Low-level Laser Therapy (00:55:19)

• Low-level laser therapy (LLLT) using red laser light is FDA-approved for hair regrowth and has few side effects.
• LLLT is delivered through devices like combs or caps, usually for 10-15 minute sessions.
• Clinical trials have shown it can slow hair loss and regrow hair in many individuals.
• The mechanism is unclear, but may involve nitric oxide's effect on mitochondria.
• Laser light disrupts enzyme interaction with the electron transport chain in mitochondria.
• This disruption may lead to mitohormesis, enhancing stem cell energy and potentially rejuvenation.
• Red laser light, capable of penetrating skin layers, might have broader beneficial body effects and is used in infrared saunas.

Platelet-rich Plasma (PRP) Injections (00:57:59)

• PRP injections, using one's own centrifuged blood, are used for hair loss and other conditions.
• PRP is rich in growth factors, exosomes, hormones, and peptides, which might rejuvenate hair follicle stem cells.
• The specific active component in PRP is unknown.
• There is potential anti-aging effects from PRP, linking to systemic rejuvenation seen in animal studies.

Hair Aging, Stress, and Gray Hair Reversal (01:00:11)

• Growth of hair in unwanted places (like ears or nose) could be due to aging-related changes in DNA structure.
• Delaying aging might prevent these changes and unwanted hair growth.
• Psychological stress is known to accelerate graying; recent studies suggest gray hair can, under some conditions, revert to its original color.
• Hair color changes are likely epigenetic, influenced by the functional state of melanocyte stem cells.
• A combination treatment tested in mice suggests a potential for reversing graying, involving drugs like cyclosporine and rapamycin analogs, which also rejuvenate mitochondria and simulate a fasting response.
• This treatment is not ready for human use, but hints at future possibilities for hair repigmentation through scientific advances.

Targeting Aging Upstream (01:06:11)

• Addressing aging pathways can impact various conditions that are downstream.
• The lessons learned from reversing skin aging and improving hair color could be applied to other organs.
• Cells share fundamental aging causes and defense pathways.
• Drugs like rapamycin, cyclosporine, and minoxidil could be tested for whole-body rejuvenation effects.
• Future treatments could potentially lead to taking pills to not only reverse aging but also regenerate and darken hair.

Today’s Takeaways (01:07:37)

• The big picture is the potential to reverse aging internally and externally.
• Future treatments may involve injectables, edibles, or topical products to deliver anti-aging molecules.
• Initially considered superficial, anti-aging research is seen as a way to improve overall health.
• Traditional health advice remains important: exercise, diet, sleep, and stress reduction.
• Looking good through healthy practices can be a byproduct of a longer life span.