Rapamycin reduces the total amount of senescent cells

Rather than simply modifying senescent cells present in the tissue, rapamycin treatment either reduces the number of cells entering senescence or increases the clearance of senescent cells
https://gethealthspan.com/blog/articles/inhibiting-skin-senescence-with-topical-rapamycin-sirolimus-for-anti-aging-skincare/40o2ogqdwaekuxak96h3iy/

https://youtu.be/8l0GVXpN2q4

Privacy policy on bio data which restricts to share for AI training on such data kills not only the owners of this data, but kills all of us.

These AI trainings can find solutions on fighting severe diseases which kill EVERY DAY 166,000 people

There should be the international law obligating everyone to share their bio data in anonymous way for radical life extension purposes.

We, in Longevity InTime, use the anonymization token, which anonymizes on the client’s end l sensitive private data (names, contacts, social security numbers & etc) and gives values of these client’s bio data parameters (e.g. glucose, cholesterol, blood pressure rate & dozens of other parameters) to data scientists in the anonymized token number, which can be associated with end user (if needed) only by the end user itself. For the rest of the world this data belongs to the token (random numbers).

The other thing, that AI can save and extend lifespan. In 500,000 hours (approximately) everyone who was involved in this discussion will die due to “natural causes”. But these natural causes can de delayed or one day even cancelled by AI. This is not just a thought, it is evidence based science.

It’s the greatest tragedy that people with such serious faces, questions and answers are focusing on the fractions of the picture (potential threat & etc), they don’t see the picture itself (that we live 30-40 years less than physically can, up to 120). If there are more than 600 recorded cases of people lived over 110 years then its possible and AI can try to do it!

Just imagine only 600, out of 109 billion of people who lived until know, plus 8 billion who lives now and big part of them will die in just 500,000 hours.

We, in Longevity InTime, use AI for simulation of clinical trials, that can speed up the outcomes of these trials and destroy so to called “longevity paradox”. When trials organizers & participants die before the end of the clinical trials process, due to natural causes, because trials take decades.

Interested in longer active life, join teterin@longevityintime.org

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Oleg Teterin

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Oleg Teterin

May the longevity be with you!

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Free course on longevity:

https://www.longevity.degree/p/longevity-medicine-101

*May 23, 2023*
Long but revealing as well as entertained article that covers interesting paths and views from scientists such as Charles Brenner (known as "the longevity skeptic"), David Sinclair and Leonard Guarente.
https://nautil.us/the-longevity-skeptic-305806/

“The field of gene therapy has made massive advancements in the last 10 years with 15 approved gene therapies. BUT some of the evidence for those approved therapies were evident in the 1990s! So regulations are still slow. They are speeding up but there is still not one aging-related or regenerative gene therapy in clinical trials (outside of follistatin that started over a decade ago for muscular dystrophy). Things are speeding up but for 110,000 people today it is too late. And this trend continues.”

Liz Parrish

Restoring Protein Elastin
Introduction:
• Our skin contains two essential proteins, elastin and collagen, which support the elasticity, resilience, and general young look of our skin. Since birth, elastin has allowed the skin to stretch and rebound, while collagen offers resilience and structural support.
• However, as we get older, the synthesis of these proteins declines, which causes the skin to lose its firmness and suppleness. Fortunately, there are a number of actions you can do to help the recovery and upkeep of collagen and elastin.
• Adopting a balanced diet high in important nutrients, shielding the skin from damaging UV rays, utilising topical treatments with healthy components, thinking about dermatological procedures, establishing good living habits, and placing a priority on getting enough sleep are a few examples.
• Our skin's elasticity and resilience are provided by the protein elastin, which is a vital part of our skin. While it is true that as we age, our ability to produce elastin declines, there are a number of things you can do to help your skin's elastin and collagen levels return to normal. Here are some recommendations based on research:
Details:
• Support via nutrition: Eating a diet that is well-balanced and rich in nutrients that support skin health might be helpful. Vitamins A, C, and E are important nutrients because they are antioxidants that help prevent oxidative damage to collagen and elastin. Additionally, the creation of collagen and elastin depends on minerals like copper and zinc. You may help supply these nutrients by including foods like fruits, vegetables, lean meats, whole grains, nuts, and seeds in your diet.
• Hydration: It's important to drink enough water to keep your skin healthy. Drinking adequate water facilitates the delivery of nutrients to the cells, particularly those responsible for the production of elastin and collagen, and keeps your skin moisturised.
• Sun protection: Prolonged sun exposure can cause the collagen and elastin fibres in the skin to break down more quickly. Maintaining these proteins requires that you protect your skin from the sun. When going outside, be careful to use a broad- spectrum sunscreen with a high SPF, wear protective clothes, and look for shade during the hottest parts of the day.
• Treatments that are applied topically: Some topical therapies may support the skin's elastin and collagen development. Look for skincare products with retinoids, peptides, vitamin C, and hyaluronic acid as components. These compounds have the potential to increase the skin's ability to produce collagen and elastin.
• Dermatological treatments: A variety of dermatological procedures can enhance the synthesis of collagen and elastin. These include of radiofrequency therapy, microneedling, and laser treatments. By boosting the synthesis of these proteins, these techniques help to rejuvenate the skin.

• Lifestyle factors: Your skin's health may be affected by certain lifestyle choices. Elastin and collagen integrity can be preserved by refraining from smoking and consuming less alcohol. Alcohol abuse can hinder collagen production, whereas smoking has been related to increased elastin breakdown.
• Adequate sleep: A good night's sleep is crucial for maintaining good skin health. The body regenerates tissues, including the skin, while we sleep. To promote healthy skin function and regeneration, aim for 7-9 hours of unbroken sleep each night.
Elastin and collagen maintenance and restoration in the skin:
• Retinoids: Retinoids are vitamin A derivatives that have been extensively researched for their capacity to increase the formation of collagen and enhance the look of ageing skin. They function by enhancing cell renewal and enhancing the production of collagen and elastin fibres. Retinoids come in over-the-counter medicines like retinol and prescription-strength formulations like tretinoin.

When taking retinoids, it's crucial to adhere to your dermatologist's instructions and suggestions because they can make skin sensitive and should be added to your skincare regimen gradually.
• Peptides: serve as the building blocks for proteins like collagen and elastin. Peptides are short chains of amino acids. Some peptides have the ability to tell the skin to make more collagen and elastin when administered topically. Palmitoyl pentapeptide and copper peptides are two examples of peptides that are frequently utilised in cosmetics.
• Vitamin C: Vitamin C is a powerful antioxidant that is essential for the production of collagen. Collagen fibres benefit from its stabilising and free radical-damage prevention properties. Additionally, vitamin C has a role in the transformation of the amino acid proline into hydroxyproline, which is required for collagen synthesis. To encourage the production of collagen and the general health of your skin, look for serums or creams containing vitamin C (ascorbic acid).
• Hyaluronic Acid: A naturally occurring component in the skin, hyaluronic acid aids in moisture retention and adds to the plumpness and flexibility of the skin. Although it doesn't directly promote the formation of elastin or collagen, it can improve the skin's look by increasing moisture and lessening the visibility of fine lines and wrinkles. Serums and moisturisers are only two examples of skincare products that include hyaluronic acid.
• Microneedling: Microneedling is a technique that uses small needles to make channels in the skin. As the skin heals itself, this process encourages the creation of collagen and elastin. Microneedling can be performed with a dermatologist's assistance or at home using dermarollers, although professional treatments often provide more noticeable results.
• Radiofrequency Therapy: Radiofrequency (RF) therapy employs radiofrequency radiation to heat the deep layers of the skin in a non-invasive manner. The regulated heat helps to tighten and firm the skin by stimulating the creation of collagen and elastin. A licenced aesthetician or dermatologist can provide RF treatment.

Conclusion:
• Despite the fact that the synthesis of elastin and collagen in our skin naturally declines as we age, there are proactive measures we can take to assist their repair and maintenance.
• We can encourage the creation and preservation of these essential proteins by using a comprehensive strategy that includes good diet, sun protection, topical treatments, dermatological procedures, healthy lifestyle choices, and enough sleep.
• While these steps might not completely reverse the effects of ageing on elastin and collagen, they can help create healthier, more elastic, and resilient skin, which helps keep our skin strong and youthful-looking as we age.
Evidence based articles and links:
• “Skin collagen through the lifestages: importance for skin health and beauty": https:// parjournal.net/article/view/3863
• "How To Improve Skin Elasticity, According To Dermatologists”: https:// www.forbes.com/sites/nomanazish/2021/08/28/how-to-improve-skin-elasticity- according-to-dermatologists/?sh=4e4d3a847a65
• "A Collagen Supplement Improves Skin Hydration, Elasticity, Roughness, and Density: Results of a Randomized, Placebo-Controlled, Blind Study”: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC6835901/
• “Diet and Skin Aging—From the Perspective of Food Nutrition”: https:// www.mdpi.com/2072-6643/12/3/870
• “Elastin”: https://my.clevelandclinic.org/health/body/22482-elastin
• “Clinical Relevance of Elastin in the Structure and Function of Skin”: https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC8239663/
• “Ways to smooth the skin by boosting collagen levels”: https:// www.medicalnewstoday.com/articles/317151
• “Radiofrequency for the treatment of skin laxity: mith or truth”: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC4631236/
• “Prevention of Ageing-The Role of Micro-Needling in Neck and Cleavage Rejuvenation: A Narrative Review”: https://pubmed.ncbi.nlm.nih.gov/35897441/

• “The roles of hyaluronic acid, collagen and elastin in the mechanical properties of connective tissues”: https://pubmed.ncbi.nlm.nih.gov/7216901/

Topical Rapamycin
Introduction:
A drug called topical rapamycin is employed in a number of dermatological procedures. It originates from the immunosuppressive qualities of the naturally occurring substance known as rapamycin, which was first found in the soil of Easter Island.
It has been demonstrated that rapamycin lowers the body's overall senescent cell count. The term "cellular senescence" describes a condition in which cells no longer have the capacity to divide and proliferate and instead experience a persistent and irreversible growth stop.
Senescent cells build up with ageing and have a role in a number of age-related illnesses and ailments. Will discuss more about Rapamycin below.
"Rapamycin reduces the total amount of senescent cells”
• It has been revealed that rapamycin, a drug produced from the substance first identified on Easter Island, has the capacity to lessen the overall amount of senescent cells in the body. Age-related cell accumulation of senescent cells, which are cells that have reached an irreversible growth halt.
• Rapamycin causes a process known as autophagy, which includes the recycling and destruction of damaged cellular components, by blocking a protein known as mTOR (mammalian target of rapamycin). Senescent cells and cell waste are removed via autophagy.
• Rapamycin therapy has been shown in several trials to reduce the number of senescent cells in a variety of organs, including the skin, liver, and adipose tissue. In several animal models, this decrease in senescent cells has been linked to a number of positive outcomes, including better tissue function, higher regenerative ability, and prolonged life.
• Studies on anti-aging and age-related diseases are increasingly focusing on the treatment of senescent cells. Senescent cell burden reduction is thought to offer therapeutic promise for a number of illnesses, including cancer, neurological disorders, and cardiovascular ailments.
• To completely comprehend the effects of rapamycin, including ideal dose and possible adverse effects, further study is still required. The effectiveness and safety of rapamycin and other senolytic treatments in humans are now being studied in clinical studies.
• The medication rapamycin is a member of the group of substances known as mTOR inhibitors. A protein kinase known as mTOR (mechanistic target of rapamycin) is essential for cell growth, metabolism, and ageing.
• Rapamycin has been shown to have potential anti-aging properties and has been found to alter a number of cellular processes via blocking mTOR.

• Numerous studies have shown that rapamycin therapy can lessen the formation of senescent cells in both animal and human cells. It is believed that rapamycin's senolytic effects are caused by a number of different pathways. Senescent cells can be selectively eliminated from the body by rapamycin by inducing apoptosis (programmed cell death) in such cells. Rapamycin can also improve the immune system's capacity to eliminate senescent cells.
• Senescent cells can contribute to tissue malfunction and encourage inflammation, which are important causes of age-related disorders, therefore reducing their number is a desired goal. Rapamycin may have the ability to lengthen life expectancy and postpone the onset of age-related diseases by eliminating or decreasing senescent cells.
• It's important to remember that the prescription medicine rapamycin is mostly utilised as an immunosuppressant to avoid organ transplant rejection and in the treatment of certain malignancies.
• Even though it has demonstrated promise as an anti-aging strategy, more study is still required to properly comprehend its long-term benefits, ideal dose regimes, and potential adverse effects in the context of ageing.
More information:
• Mechanism of action: Rapamycin works by inhibiting the protein kinase mTOR, which is involved in cellular activities such protein synthesis, cell proliferation, and autophagy. Rapamycin slows or stops some biological processes, such as the buildup of senescent cells, by blocking mTOR.
• Senescent cell clearance: Rapamycin has been demonstrated to improve senescent cell clearance through a number of ways. Senescent cells can experience apoptosis, or cell death, which enables the body to get rid of them. Rapamycin also activates the immune system's immunosurveillance mechanism, which helps it identify and destroy senescent cells.
• Benefits for healthspan: Removing or decreasing senescent cells has been associated with a number of healthspan advantages. Chronic inflammation, tissue malfunction, and age-related illnesses including cancer, cardiovascular disease, and neurological disorders are all linked to senescent cells. Rapamycin may assist in alleviating certain age-related diseases and enhancing general health and longevity by lowering the load of senescent cells.
• Studies on animals: Rapamycin has showed encouraging effects in reducing senescent cells. It has been shown that rapamycin therapy in mice reduces the development of senescent cells in a variety of organs, including the liver, adipose tissue, and skeletal muscle. Additionally, these research have demonstrated improved ageing characteristics and lengthened longevity in certain mice models.
• Studies on humans: Although rapamycin has been the subject of substantial research in animals, nothing is known about how it affects senescent cells in people. There are now some clinical trials looking at how rapamycin affects ageing and age-related

disorders. In these studies, rapamycin and its analogues will be tested on humans to determine their safety, effectiveness, and any possible adverse effects.
• Considerations and restrictions: Rapamycin is a prescription medication with possible adverse effects, and research on its long-term impact on ageing and human health is ongoing. Research is still being conducted on the best dose, length of therapy, and possible side effects of rapamycin for anti-aging objectives.
Conclusion:
• In conclusion, the claim that rapamycin lowers the overall number of senescent cells is supported by the available data. Animal preclinical investigations have shown that rapamycin therapy can reduce the formation of senescent cells in a variety of organs.
• Senescent cells may undergo apoptosis due to rapamycin, which also makes the immune system more effective in eliminating them. To completely comprehend the effects of rapamycin on senescent cells in people and to establish the ideal dosage schedules and potential adverse effects connected with its usage for this purpose, more study is necessary.
• Rapamycin should thus be used cautiously and in accordance with medical advice even if it has promise as a senolytic drug.
Evidence based articles and links:
• “Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial”: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC6925069/
• “Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2‐independent mechanism”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418203/
• “The mTOR inhibitor Rapamycin protects from premature cellular senescence early after experimental kidney transplantation”: https://journals.plos.org/plosone/article? id=10.1371/journal.pone.0266319
• “Effect of rapamycin on aging and age-related diseases—past and future”: https:// link.springer.com/article/10.1007/s11357-020-00274-1
• “Progressive slowdown/prevention of cellular senescence by CD9-targeted delivery of rapamycin using lactose-wrapped calcium carbonate nanoparticles”: https:// www.nature.com/articles/srep43299
• “Targeting senescent cells: approaches, opportunities, challenges”: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC6949083/ #:~:text=SUPPRESS%20SENESCENT%20CELLS-,Senolytics,in%20senescent%20cel ls%20%5B16%5D.
• “Cell senescence, rapamycin and hyperfunction theory of aging”: https:// www.tandfonline.com/doi/full/10.1080/15384101.2022.2054636

Longevity Genes

List of genes responsible for Longevity:

The complicated attribute of longevity is impacted by a number of genetic, environmental, and lifestyle variables. Even while research into the genetic causes of longevity is ongoing, it's crucial to remember that no one gene can be entirely to blame for determining lifetime.

However, certain genes have been linked to long life and are thought to contribute to the ageing process. Based on research, the following genes have been associated with long life:

FOXO3: This gene has been linked to remarkable human lifespan and is involved in controlling the insulin/insulin-like growth factor (IGF) signalling pathway. Source: “FOXO3 and Exceptional Longevity: Insights From Hydra to Humans”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295567/

SIRT1: This gene is a member of the sirtuin gene family, which plays a variety of roles in cellular functions such DNA repair, metabolism, and stress response. SIRT1 has been associated with increased longevity in a number of model species. Source: “The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651129/

MTOR: The protein kinase known as the mammalian target of rapamycin (mTOR) controls cellular development, metabolism, and ageing. Numerous creatures have showed longer lifespans when mTOR signalling is inhibited. Source: “Mammalian Target of Rapamycin”: https://www.sciencedirect.com/topics/neuroscience/mammalian-target-of-rapamycin

APOC3: Variants of the APOC3 gene have been linked to prolonged longevity and a decreased risk of cardiovascular illnesses. Source: “ApoC-III: a potent modulator of hypertriglyceridemia and cardiovascular disease”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524519/

CETP: The cholesteryl ester transfer protein (CETP) gene has genetic variants that have been linked to increased lifespan and a decreased chance of developing age-related disorders. Source: “Cholesteryl Ester Transfer Protein (CETP) Genotype and Reduced CETP Levels Associated With Decreased Prevalence of Hypertension”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878255/

TERT: Telomeres, which are protective structures at the ends of chromosomes, are maintained by telomerase reverse transcriptase (TERT). Telomere length and longevity variations have been linked to variations in the TERT gene. Source: “Telomeres and Telomere Length: A General Overview”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139734/

APOB: Apolipoprotein B (APOB) gene variations have been associated with remarkable lifespan and a lower risk of cardiovascular illnesses. Source: “Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540246/

KLOTHO: A protein that has been linked to ageing and lifespan is encoded by the KLOTHO gene. KLOTHO gene variations have been linked to increased longevity and cognitive performance. Source: “Klotho and aging”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743784/

NRF2: The nuclear factor erythroid 2-related factor 2 (NRF2) gene controls cellular stress defences and antioxidant responses. In model organisms, activation of NRF2 has been associated with longer life. Source: “The KEAP1-NRF2 System in Healthy Aging and Longevity”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750203/#:~:text=The%20KEAP1%2DNRF2%20activity%20and%20longevity.&text=In%20experimental%20models%2C%20mild%20activation,tolerance%2C%20accelerates%20the%20aging%20process.

PON1: The paraoxonase 1 (PON1) gene encodes an enzyme that is involved in lipid metabolism and oxidative stress defence. Age-related illness risk has been shown to be lower and lifespan has been linked to variations in the PON1 gene. Source: “PON1 is a longevity gene: results of a meta-analysis”: https://pubmed.ncbi.nlm.nih.gov/19376276/#:~:text=Patients%20carrying%20PON1%20codon%20192,represented%20in%20long%2Dliving%20individuals.

GSTM1: The glutathione S-transferase mu 1 (GSTM1) gene results in the production of an enzyme that aids in the detoxification of a number of substances. Increased longevity and better health outcomes have been linked to certain GSTM1 gene variants. Source: “GSTM1”: http://www.cancerindex.org/geneweb/GSTM1.htm#:~:text=GSTM1%20is%20a%20glutathione%20S,a%20range%20of%20different%20cancers.

HSPA1A/HSPA1B: These genes are members of the heat shock protein (HSP) family and are involved in the regulation of protein quality and the response of cells to stress. Longevity and enhanced stress tolerance have been related to variations in the HSPA1A and HSPA1B genes. Source: “Anti-Inflammatory Heat Shock Protein 70 Genes are Positively Associated with Human Survival”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631775/

PINK1: PTEN-induced putative kinase 1 (PINK1) gene mutations have been linked to Parkinson's disease. A longer lifespan and resistance to cellular stress have also been associated with certain PINK1 gene variants. Source: “PINK1 signaling in mitochondrial homeostasis and in aging (Review)”: https://www.spandidos-publications.com/10.3892/ijmm.2016.2827

BPIFB4: The innate immune system is regulated by the gene BPI fold-containing family B member 4 (BPIFB4). Alterations in the BPIFB4 gene have been linked to a longer life expectancy and a lower chance of developing age-related disorders. Source: “The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy”: https://pubmed.ncbi.nlm.nih.gov/36635236/


TP53: The TP53 gene produces the tumour protein p53, which is essential for DNA repair, controlling the cell cycle, and causing apoptosis. Longevity and a lower chance of developing cancer have been associated with certain TP53 gene variants. Source: “The Regulation of Aging and Longevity”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135645/

Should they all be applied at once? Or maybe it depends on the individual?

It is uncommon to employ the genes linked to long life as a single package or treatment. Instead, they behave as possible predictors of characteristics that could support lifespan. These genes can have a complicated and variable impact on longevity depending on the person, their genetic composition, and their environment.

It's critical to remember that genetics only accounts for a small portion of lifespan. Diet, exercise, stress management, and environmental influences are all important lifestyle aspects.

It is also difficult to separate the influence of specific genes in a complex characteristic like lifespan since the interaction between genes and environment is a dynamic process.

The majority of the present knowledge on genes linked to long life is derived from observational research and genetic association studies, which offer correlations rather than causes.

As a result, it is not advised to utilise genetic data for lifespan as a firm prescription or treatment strategy. Instead, it is generally agreed that the ideal method for maintaining lifespan and wellbeing is a complete approach that includes a healthy lifestyle, frequent medical checkups, and proactive treatment of risk factors.

Evidence based articles and links:

“Genetics of extreme human longevity to guide drug discovery for healthy ageing”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912776/

“The Genetics of Aging”: https://www.annualreviews.org/doi/10.1146/annurev.genom.2.1.435