Why cellular senescence is more than just one of the 12 hallmarks of aging - It’s a central pillar of aging
3 min read
OCT 4, 2023
LONGEVITY
Why cellular senescence is more than just one of the 12 hallmarks of aging - It’s a central pillar of aging
3 min read
OCT 4, 2023
LONGEVITY
Aging is a systemic and multifaceted process with many root causes. In fact, there are twelve hallmarks of aging that contribute to all aspects of human aging–from fine lines on our face to age-related diseases like Alzheimer’s and arthritis. But recent breakthroughs in longevity science have revealed that not all twelve hallmarks of aging are equal. Some hold greater importance–and therefore greater potential as therapeutic targets in the aging process.
Aging is a systemic and multifaceted process with many root causes. In fact, there are twelve hallmarks of aging that contribute to all aspects of human aging–from fine lines on our face to age-related diseases like Alzheimer’s and arthritis. But recent breakthroughs in longevity science have revealed that not all twelve hallmarks of aging are equal. Some hold greater importance–and therefore greater potential as therapeutic targets in the aging process.
One mechanism of aging, cellular senescence, has been identified by longevity scientists as central to the other eleven hallmarks of aging. By targeting cellular senescence, scientists hope to unravel the interconnected web of aging factors by developing breakthrough therapies that could help people live longer lives in good health. Let’s take a closer look at why cellular senescence is central to aging and how targeted therapies can effectively reverse this process in the skin and our bodies as a whole.
One mechanism of aging, cellular senescence, has been identified by longevity scientists as central to the other eleven hallmarks of aging. By targeting cellular senescence, scientists hope to unravel the interconnected web of aging factors by developing breakthrough therapies that could help people live longer lives in good health. Let’s take a closer look at why cellular senescence is central to aging and how targeted therapies can effectively reverse this process in the skin and our bodies as a whole.
01
What is cellular senescence?
In the 1960s, Leonard Hayflick determined that cells can only replicate and divide about 50 times before they cease to function due to the gradual accumulation of damage. [1] This normal aging process, called cellular senescence, is biologically intended to promote tissue homeostasis and prevent the proliferation of damaged cells that could potentially lead to tumors. When we’re young and healthy, our immune systems efficiently eliminate senescent cells as they arise, but this process becomes less efficient as we age. Plus, throughout our lives, we continuously encounter factors that induce premature senescence, such as oxidative stress [2], inactivation of tumor suppressor genes [3], and infections [4]. This results in an increasing accumulation of senescent cells in our bodily tissues. Like rotten apples that spoil the bunch, these cells drive neighboring cells into senescence by releasing pro-aging and inflammatory signals. This process significantly accelerates aging and age-related diseases. Read more on cellular senescence here.
01
What is cellular senescence?
In the 1960s, Leonard Hayflick determined that cells can only replicate and divide about 50 times before they cease to function due to the gradual accumulation of damage. [1] This normal aging process, called cellular senescence, is biologically intended to promote tissue homeostasis and prevent the proliferation of damaged cells that could potentially lead to tumors. When we’re young and healthy, our immune systems efficiently eliminate senescent cells as they arise, but this process becomes less efficient as we age. Plus, throughout our lives, we continuously encounter factors that induce premature senescence, such as oxidative stress [2], inactivation of tumor suppressor genes [3], and infections [4]. This results in an increasing accumulation of senescent cells in our bodily tissues. Like rotten apples that spoil the bunch, these cells drive neighboring cells into senescence by releasing pro-aging and inflammatory signals. This process significantly accelerates aging and age-related diseases. Read more on cellular senescence here.
02
How is cellular senescence related to the other eleven hallmarks of aging?
Before we dive into the science, here’s a quick look at the twelve hallmarks of aging:(Note: Hallmarks 1-9 have been established since 2013, and 10-12 were recently added in 2023)
- Genomic instability
- Telomere attrition
- Epigenetic alterations
- Loss of proteostasis
- Deregulated nutrient sensing
- Mitochondrial dysfunction
- Cellular senescence
- Stem cell exhaustion
- Altered intercellular communication
- Chronic inflammation
- Disabled macroautophagy
- Dysbiosis
02
How is cellular senescence related to the other eleven hallmarks of aging?
Before we dive into the science, here’s a quick look at the twelve hallmarks of aging:(Note: Hallmarks 1-9 have been established since 2013, and 10-12 were recently added in 2023)
- Genomic instability
- Telomere attrition
- Epigenetic alterations
- Loss of proteostasis
- Deregulated nutrient sensing
- Mitochondrial dysfunction
- Cellular senescence
- Stem cell exhaustion
- Altered intercellular communication
- Chronic inflammation
- Disabled macroautophagy
- Dysbiosis
Cellular senescence is arguably the most detrimental of these twelve biological phenomena and the one that links them all together. Senescence can be caused by five of the twelve hallmarks that are primary factors of cell aging: 1) genomic instability, 2) telomere attrition, 3) epigenetic alterations, 6) mitochondrial dysfunction, and 11) disabled macroautophagy. These factors can all be induced by both internal triggers and environmental factors like UV rays, environmental toxins, and daily stress.[5] As senescent cells accumulate in tissues across the body, they drive further aging by triggering the remaining six hallmarks of aging: 9) altered intercellular communication, 5) disruption of nutrient signaling, 4) irregular protein manufacturing, 8) exhaustion of replacement stem cells, 10) chronic inflammation, and 12) dysbiosis.[6] Because senescence is directly related to all other hallmarks, it is considered a “central pillar” of aging.
Cellular senescence is arguably the most detrimental of these twelve biological phenomena and the one that links them all together. Senescence can be caused by five of the twelve hallmarks that are primary factors of cell aging: 1) genomic instability, 2) telomere attrition, 3) epigenetic alterations, 6) mitochondrial dysfunction, and 11) disabled macroautophagy. These factors can all be induced by both internal triggers and environmental factors like UV rays, environmental toxins, and daily stress.[5] As senescent cells accumulate in tissues across the body, they drive further aging by triggering the remaining six hallmarks of aging: 9) altered intercellular communication, 5) disruption of nutrient signaling, 4) irregular protein manufacturing, 8) exhaustion of replacement stem cells, 10) chronic inflammation, and 12) dysbiosis.[6] Because senescence is directly related to all other hallmarks, it is considered a “central pillar” of aging.
Telomere damage, epigenetic dysregulation, DNA damage, mitochondrial dysfunction, and disabled macroautophagy are primary drivers of damage in aging. Several of these drivers of damage can induce senescence. Senescence can in turn drive the consequential aging hallmarks in response to damage: stem cell exhaustion and altered intercellular communication. Other responses to damage, such as proteostatic dysfunction, chronic inflammation, dysbiosis, and nutrient signaling disruption, are also integrally linked with senescence response. [6]
Telomere damage, epigenetic dysregulation, DNA damage, mitochondrial dysfunction, and disabled macroautophagy are primary drivers of damage in aging. Several of these drivers of damage can induce senescence. Senescence can in turn drive the consequential aging hallmarks in response to damage: stem cell exhaustion and altered intercellular communication. Other responses to damage, such as proteostatic dysfunction, chronic inflammation, dysbiosis, and nutrient signaling disruption, are also integrally linked with senescence response. [6]
03
Why is cellular senescence a prime target for longevity therapeutics?
Because cellular senescence is so central to other aging processes, preventing and reversing cellular senescence is a very effective method for extending healthspan–from skin health to whole-body wellbeing. Senescent cells in the skin can contribute to wrinkles, crepiness, and disease progression [7] while senescent cell accumulation in other tissues can contribute to diseases such as osteoarthritis [8] and type 2 diabetes [9]. Due to its role in the etiology of many age-related diseases, preventing and disrupting senescence can effectively delay aging, making it a prime target for longevity therapeutics.
03
Why is cellular senescence a prime target for longevity therapeutics?
Because cellular senescence is so central to other aging processes, preventing and reversing cellular senescence is a very effective method for extending healthspan–from skin health to whole-body wellbeing. Senescent cells in the skin can contribute to wrinkles, crepiness, and disease progression [7] while senescent cell accumulation in other tissues can contribute to diseases such as osteoarthritis [8] and type 2 diabetes [9]. Due to its role in the etiology of many age-related diseases, preventing and disrupting senescence can effectively delay aging, making it a prime target for longevity therapeutics.
04
What are senotherapeutics and how do they target cellular senescence?
Senotherapeutics are a class of molecules that have been shown to prevent the accumulation and/or enhance the removal of senescent cells. Data from animal and clinical models suggest that senotherapeutic drugs and peptide therapies can effectively target and reverse cellular senescence in two ways:[10]
- Senolytics: enhance the specific killing of senescent cells. For a senolytic to be safe it should target senescent cells without affecting the viability of neighboring healthy cells.
- Senomorphics: change senescence phenotypes by enhancing the cell function or inhibiting the harmful signals secreted by senescent cells that drive neighboring cells into senescence (also calledsenescence-associated secretory phenotype or SASP).
04
What are senotherapeutics and how do they target cellular senescence?
Senotherapeutics are a class of molecules that have been shown to prevent the accumulation and/or enhance the removal of senescent cells. Data from animal and clinical models suggest that senotherapeutic drugs and peptide therapies can effectively target and reverse cellular senescence in two ways:[10]
- Senolytics: enhance the specific killing of senescent cells. For a senolytic to be safe it should target senescent cells without affecting the viability of neighboring healthy cells.
- Senomorphics: change senescence phenotypes by enhancing the cell function or inhibiting the harmful signals secreted by senescent cells that drive neighboring cells into senescence (also calledsenescence-associated secretory phenotype or SASP).
05
What is the potential for senotherapeutics in the longevity field?
Along with longevity-focused lifestyle habits like good nutrition and regular exercise, the use of senotherapeutics may one day be a powerful tool for preventing age-related diseases and reversing aging. Nearly 30 clinical trials are currently investigating the role of senotherapeutics in treating various cancers, aging phenotypes, neurodegenerative diseases, and infections. [11]When it comes to skin longevity, the future is already here. The researchers at OneSkin examined nearly one thousand potential senotherapeutic peptides in the laboratory to discover one lead peptid eand further optimize it to become OS-01: the first peptide proven to reduce skin’s biological age. [12] Lab studies on human skin samples and cells have shown that the OS-01 peptide reduces the number of senescent cells in the skin by up to 50%.[12] These results show that by reducing cellular senescence, the OS-01 peptide can slow the aging process and associated aging processes, ensuring that skin behaves, appears, and feels like younger skin for longer. [12]
05
What is the potential for senotherapeutics in the longevity field?
Along with longevity-focused lifestyle habits like good nutrition and regular exercise, the use of senotherapeutics may one day be a powerful tool for preventing age-related diseases and reversing aging. Nearly 30 clinical trials are currently investigating the role of senotherapeutics in treating various cancers, aging phenotypes, neurodegenerative diseases, and infections. [11]When it comes to skin longevity, the future is already here. The researchers at OneSkin examined nearly one thousand potential senotherapeutic peptides in the laboratory to discover one lead peptid eand further optimize it to become OS-01: the first peptide proven to reduce skin’s biological age. [12] Lab studies on human skin samples and cells have shown that the OS-01 peptide reduces the number of senescent cells in the skin by up to 50%.[12] These results show that by reducing cellular senescence, the OS-01 peptide can slow the aging process and associated aging processes, ensuring that skin behaves, appears, and feels like younger skin for longer. [12]
Key Takeaways:
- Cellular senescence is at the center of all other hallmarks of aging and can mediate many aging phenotypes.
- Targeting cellular senescence effectively inhibits all other hallmarks of aging, such as altered cellular communication, cellular dysfunction, and irreversible cellular damage.
- Therapeutic interventions against cellular senescence can significantly reduce symptoms of aging, as senescence-mediated aging is a leading indicator of many diseases.
- Senotherapeutics can effectively target aging at the cellular level to prevent age-related diseases and extend healthspan - the ultimate goal of longevity science.
Key Takeaways:
- Cellular senescence is at the center of all other hallmarks of aging and can mediate many aging phenotypes.
- Targeting cellular senescence effectively inhibits all other hallmarks of aging, such as altered cellular communication, cellular dysfunction, and irreversible cellular damage.
- Therapeutic interventions against cellular senescence can significantly reduce symptoms of aging, as senescence-mediated aging is a leading indicator of many diseases.
- Senotherapeutics can effectively target aging at the cellular level to prevent age-related diseases and extend healthspan - the ultimate goal of longevity science.
References
- https://www.thelancet.com/article/S0140-6736(11)60908-2/fulltext
- http://www.ncbi.nlm.nih.gov/pubmed/29747066
- https://pubmed.ncbi.nlm.nih.gov/17136094/
- https://pubmed.ncbi.nlm.nih.gov/34103349/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344376/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748990/
- https://pubmed.ncbi.nlm.nih.gov/26286607/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785239/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546206/
- https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00300-7/fulltext
- https://www.jci.org/articles/view/158450#SEC3
- https://www.nature.com/articles/s41514-023-00109-1
References
- https://www.thelancet.com/article/S0140-6736(11)60908-2/fulltext
- http://www.ncbi.nlm.nih.gov/pubmed/29747066
- https://pubmed.ncbi.nlm.nih.gov/17136094/
- https://pubmed.ncbi.nlm.nih.gov/34103349/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344376/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748990/
- https://pubmed.ncbi.nlm.nih.gov/26286607/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785239/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546206/
- https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00300-7/fulltext
- https://www.jci.org/articles/view/158450#SEC3
- https://www.nature.com/articles/s41514-023-00109-1
Reviewed by Alessandra Zonari, PhD, Chief Scientific Officer (CSO) and Co-Founder of OneSkin
Alessandra earned her Master’s degree in stem cell biology, and her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil in collaboration with the 3B’s Research Group in Portugal. Alessandra did a second post-doctoral at the University of Coimbra in Portugal. She is a co-inventor of three patents and has published 20 peer-reviewed papers in scientific journals.
Reviewed by Alessandra Zonari, PhD, Chief Scientific Officer (CSO) and Co-Founder of OneSkin
Alessandra earned her Master’s degree in stem cell biology, and her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil in collaboration with the 3B’s Research Group in Portugal. Alessandra did a second post-doctoral at the University of Coimbra in Portugal. She is a co-inventor of three patents and has published 20 peer-reviewed papers in scientific journals.
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The Top 5 Benefits of Zinc Oxide for Skin
Understanding Marionette Lines: Causes and Prevent...
How to Help Your Skin Act Younger
The Science of Sunscreen: Understanding the Optima...
Better Elasticity, More Firmness: Discover OS-01 E...
Symptoms and Causes of Melasma on Face
Beyond UV Protection: 7 Surprising Ways Sunscreen ...
Making Sense of Sunscreen: Understanding the Diffe...
Navigating Anti-Aging Skincare: The industry, the ...
Sun Spots: Causes & 3 Prevention Tips
Navigating Sunscreen Labels: Unwanted Ingredients ...
How to Prevent Skin Aging Before It Starts
Face vs. Body Sunscreen: Can You Use Body Sunscree...
Sun Damaged Skin: What it is, how you can prevent ...
A Comprehensive Guide to Understanding the Differe...
How to Strengthen Your Skin: A Guide to Thicker, H...
An In-Depth Look at Glycerin: What is it and What ...
Exploring the Benefits of Glycerin for Skin Health
Exploring the Difference Between Hydrating and Moi...
3 Natural Ways to Keep Your Skin Hydrated and Glow...
How To Create A Hydrating Skin Care Routine For Dr...
Senotherapeutics, Senolytics, and Senomorphics -- ...
Cleansing 101: How to Wash Your Face the Right Way...
4 Essential Face Cleansing Steps to Achieving a Ra...
Scientific Breakthrough: OneSkin’s scientists show...
Dry Skin 101: How To Identify This Skin Type
How OS-01 Can Help Your Collagen Levels As You Age...
Developing a Skin Care Routine for Normal Skin: 4 ...
What is Normal Skin & Do I Have This Skin Type?
A Step-by-Step Guide to Creating the Perfect Skin ...
Understanding Oily Skin: Causes & Characteristics
7 Keys to Understanding Menopause and Skin Changes
Is This The Root Cause of Aging?
UV Damage Increases Cellular Senescence. Here's Ho...
Our Research Has Been Published in npj Aging
How To Reduce Hyperpigmentation by Targeting Cellu...
4 Steps to Crafting the Perfect Skin Care Routine ...
A Comprehensive Guide to Understanding and Managin...
An In-Depth Look At The Benefits Of Moringa Oil Fo...
How to Tighten the Skin Under Your Eyes
7 Causes For Crepey Skin Under Eyes
101 Guide To Restoring Dry Skin Around The Eyes
How is OS-01 EYE different from OS-01 FACE?
How to Remove Lingering Dead Skin Cells On the Fac...
Safe Beauty, Validated: Why OneSkin trusts SkinSAF...
Hallmarks of Aging
What is Sensitive Skin?
Tight Feeling Skin: 3 Reasons Why
3 Skin Tightening Ingredients To Help Boost Skin H...
How OS-01 Works on Mature Skin
Is Fragrance Bad for Your Skin?
Are Parabens Bad for Your Skin?
Target Cellular Senescence with the Highest Concen...
Can a Plant-Based Diet Really Increase Your Health...
Eye Skin Ages Faster: Here’s How OS-01 Can Help
Gut Health and Skin: How Are They Connected?
How OS-01 EYE Supports the Ultra-Thin Skin Around ...
The Science Behind Why The Skin Around the Eyes Ag...
How Do You Know When to Stop Using Retinol?
How To Heal Skin From Picking Your Face Too Much
6 Factors That Contribute to Slow Skin Healing
4 Foods To Avoid During Wound Healing & Why
A Complete Guide to the 4 Stages of Wound Healing
Collagen And Elastin: What Role Do They Play In Sk...
What is the Function of Skin as a Protective Barri...
Why We Want Skin To Be More, Not Less
More Than Skin Deep: How Physical Touch Predicts L...
What is Skin Inflammation? What Causes it?
How to Reverse (or Prevent) Aging Skin
Yes, You Need Sunscreen During Winter
Can You Use Hyaluronic Acid with Retinol?
Exploring the skin’s purpose in whole-body health
Stressed Skin: 4 Stress Effects on the Skin
What Does Hyaluronic Acid Do For Your Skin?
Good Genes vs. Good Habits: Which Impacts Your Lon...
How Does Sunscreen Work? How Long Does it Last?
What is the Best Skin Care Regimen for Aging Skin?
What happens to skin as a person ages?
What Causes Dark Circles Under and Around Your Eye...
How to Brighten Eyes and Under-Eyes
Invasive vs. Non-Invasive Skincare: The pros and c...
6 Benefits of Jojoba Oil
What are the Benefits of Sulforaphane?
What is Sustainable Packaging for Cosmetic Product...
7 Benefits of Andiroba Oil For Skin
Why is my Skin Peeling on My Face?
What Are The Causes Of Dry, Flaky Skin On Your Fac...
PREP enhances the effects of OS-01 FACE, and the p...
This is the Data to Look For When Choosing Skin Ca...
Why cellular senescence is more than just one of t...
Allantoin For Skin: A Comprehensive Guide
Ceramides For Skin: Everything You Need to Know
A Simplified Guide To The Different Skin Texture T...
How OS-01 Works With Different Skin Types
How To Smooth Skin Texture On The Face: 4 Expert T...
What Causes Crepey Skin & Can It Be Avoided Altoge...
Does Niacinamide Help With Acne & Scarring?
Skin Microbiome: What It Is, Why it’s Important, A...
What Foods Cause Acne and Which Fight Against It?
The 101 Guide To Understanding Acne-Prone Skin
The Top 4 Prickly Pear Benefits for Skin
What Is Exfoliation & Is It A Necessary Measure Fo...
OneSkin Notable Mention: Dave Asprey's The Human U...
How to Incorporate OneSkin’s OS-01 Topical Supplem...
Clean Beauty: What “clean” really means and why “s...
Retinol 101: Debunking Retinol as the Gold Standar...
Menopause & Skin: What you need to know
Take an Inside Look into Our Cutting-Edge R&D Plat...
101 Guide on The Benefits of Cleansing Your Face
How OneSkin Developed the OS-01 Peptide
Cleanser Vs. Face Wash: Which Should I Reach For?
Five Common Skin Problems Experienced in Perimenop...
You’re only as old as you feel, scientists are fin...
Collagen For Menopause: Why Is It Necessary For He...
Get to Know OneSkin’s Topical Supplements:
...OS-
The Top 3 Benefits of Peptides for Skin
How to Use Peptides In Your Skincare Regimen to Op...
Peptides vs Retinol: Is One Better For Increasing ...
What Is Causing the Uneven Skin Tone On Your Body?
How To Boost Skin Moisture For Your Entire Body Fr...
Three Ways To Extend Your Skinspan Starting With Y...
What Are Free Radicals and How Do They Impact Skin...
The Connection Between Mental Health, Age Percepti...
The Top 6 Best Antioxidants For Skin Health and Lo...
What are Zombie Cells & How Can We Remove Them?
SKIN CARE IS HEALTH CARE: WHY EXTENDING YOUR SKINS...
How chronic stress makes you age faster
What is Epidermal Thickness & Why Does it Matter?
Cell Turnover & Why It Slows As We Age
OneSkin Notable Mention: OneSkin Featured In Tony ...
101 Guide To Skin Tightening + 7 Noninvasive Metho...
How to Reduce Skin Inflammation & Redness
Niacinamide Vs Retinol: How Do They Compare?
What Is Causing the Uneven Skin Tone On Your Body?
Why Is Nutrient Absorption Key To Better Skin Heal...
OneSkin Notable Mention: LifeSpan Episode 6 | The ...
The Top 10 Best Foods for Skin Repair
Skin Hyperpigmentation 101: What It Is & How To Tr...
Are There Dangers of Retinol Cream Use?
What is Skin Elasticity & How Can You Improve It?
Celebrating Black History Month: A Discussion With...
Representation of the Black Community in Skin Care...
Our Story: Learn more about the history of OneSkin...
What Is Senescence & Its Relationship To Aging?
Winter Skincare - How To Prevent Dry Skin this Sea...
Special Announcement: OneSkin to Donate 1% of Sale...
Biological Age: What is Biological Age, Why Does i...
What your skincare routine is missing (Hint. It’s ...
What is a peptide?
Peptides: the first piece of th...
Peptides: the first piece of th...
Where Skin Health Meets Longevity
Health Is The New Wealth
The Correlation Between Sleep and Skin: Why It Mat...
How Relationships, Community, & Social Interaction...
OneSkin launches MolClock, the first skin-specific...
Calorie Restriction And Intermittent Fasting: Eati...
Healthspan: A New Way To Think About Aging