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The Hallmarks of aging

Aging is something we all go through, and scientists have always been curious about it. As time goes on, our bodies don’t work as well as they used to. This means we might get sick more often or take longer to heal. Some of us might even face bigger health problems like heart diseases or cancer. A famous study called “The Hallmarks of Aging” listed nine main reasons why we age. Then, in 2022, researchers in Copenhagen added five more reasons to that list. All this research helps us better understand the changes happening in our bodies as we grow older.

At Purovitalis, we’re deeply invested in understanding these hallmarks of aging. We believe that by focusing on them, we can create supplements that truly support our bodies as we age. But we also know that science can be complicated. That’s why we’re committed to explaining these hallmarks in a way that’s easy for everyone to understand. Our goal is to bridge the gap between complex scientific concepts and everyday knowledge, ensuring you’re well-informed and confident in the choices you make for your health.

Close-up of a young child's hand gently holding the wrinkled hand of a grandma, symbolizing the connection between generations and the hallmarks of aging and causes of aging.

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All the Hallmarks of Aging

Let’s take a closer look at these 14 hallmarks to better understand what happens in our body during the aging process:

Primary causes of aging are the main hallmarks.
Accumulating causes of aging is caused by long term small damages

1/ DNA damage

Genomic Instability

Think of your DNA as your body’s instruction manual. Genome instability can blur these instructions due to errors from DNA replication or cellular stress. While minor DNA damages aren’t always harmful, they can accumulate over time, causing cells to malfunction and contribute to aging.

If a cell has too many errors, especially in the mitochondria (the cell’s energy producers), it might not work efficiently. However, substances like Resveratrol, magnesium, vitamin B, melatonin, creatine, and NMN can support healthy mitochondrial function.

2/ Loss of DNA protection

Telomere Shortening

Think of your DNA as a shoelace, with telomeres resembling the small plastic tips at the ends. These telomeres protect our essential DNA.

Why are Telomeres Associated with Aging?

Telomeres prevent our DNA from sticking to other cellular components. If DNA is the body’s instruction manual, telomeres ensure these instructions remain separate and undamaged. They also regulate how often a cell can divide. As cells divide, telomeres shorten, acting like a countdown. When they become too brief, the cell stops dividing, which can lead to cell aging or damage. Some researchers believe this process might be tied to human aging. Preserving our telomeres could potentially extend our healthspan.

3/ Gene expression compromised

Epigenetic Alterations: A Shift in Gene Expression

Epigenetic changes are like switches that can turn certain parts of our DNA on or off. They don’t change the DNA itself but can affect how it works. These changes can be influenced by our diet, stress, and things in our environment.

As we age, these switches can affect things like inflammation and how our cells produce energy. If too many switches are in the wrong position, it can make us age faster.

By understanding and managing these switches, we might be able to age more healthily. Simple things like eating well, reducing stress, and avoiding harmful habits like smoking can help keep these switches in the right position.

4/ Protein balance gets disrupted

Proteostasis loss

As we age, our bodies might struggle to keep proteins in check, leading to issues like inflammation and organ problems. If too many damaged proteins accumulate, it can speed up aging and cause diseases.

The good news? We can help our bodies manage proteins. Eating less, fasting, and following diets like the Mediterranean or DASH can help. Plus, living a stress-free life is essential, as stress can disrupt our protein balance and overall health.

5/ Gut bacteria unbalanced

Microbiome disturbances (new)

A recent 2022 study from Copenhagen highlighted a new aspect of aging. The tiny organisms in our gut, known as the gut microbiome, undergo changes over time. There’s a shift in the type of microbes and a decrease in species variety. Additionally, barriers in our body, like the gut wall, can weaken, leading to inflammation. These alterations in gut health can result in inflammation that affects our overall well-being.

Maintaining a healthy gut can involve lifestyle changes such as eating healthy fats, drinking plenty of water, and staying active.

Table graphic comparing the potential benefits of NMN, Resveratrol, Quercetin, Spermidine, and CA-AKG on the hallmarks of aging, showcasing how each compound might influence the causes of aging.

*These statements are not yet been officially established by the (European) authorities and are based on research articles.

6/ Food processing regulation issues

Deregulated Nutrient Sensing

Nutrient sensing is when our bodies manage the use and storage of the food we eat. In our youth, this system works efficiently, helping with energy and cell repair. But as we age, it can become less accurate. This can lead to issues like inefficient processing of sugars or fats, weight gain, and inflammation. When this system is off, it can also disrupt autophagy, our cells’ cleaning process. This disruption can speed up aging and lead to age-related diseases

7/ Energy production decline

Mitochondrial dysfunction

Mitochondrial dysfunction relates to a decline in our cells’ energy production. When cells have ample nutrients, they store energy. When nutrients are scarce, cells focus on repair. However, sometimes cells don’t react properly due to issues with nutrient-sensing pathways. Some proteins play a role in cell metabolism and aging. One way to address this is by reducing calorie intake by 10% to 30%, ensuring essential nutrients are still consumed. This approach has been shown to boost health and longevity.

Mitochondria, our cells’ powerhouses, produce most of the energy we need. But this process also releases harmful particles called free radicals. Over time, these particles damage the mitochondria, leading to less efficient energy production, DNA damage, and protein imbalances. As we age, we also have fewer mitochondria, contributing to muscle weakness and a less robust immune system.

8/ Cells lose their ability to divide

Cellular senescence

Senescent cells are old or damaged cells that stop dividing and no longer help the tissues where they live. These cells not only become inactive but also send harmful signals that can turn healthy cells senescent too. Over time, as more of these senescent cells build up, they can cause problems in our body. They can make our tissues stiff, reduce their function, and lead to age-related diseases.

In simple terms, while having some old cells is natural, too many of them can speed up the aging process and cause health issues.

9/Increase in persistent inflammation

Inflammation (new)

Inflammation is a key sign of aging, often referred to as “inflammaging.” As we grow older, a constant, low-level inflammation can develop, which is linked to many age-related diseases. Researchers believe this type of inflammation is so significant that it deserves special attention when discussing aging factors. This inflammation doesn’t just stand alone; it can affect other aspects of our health, including cell behavior and gut balance. While there are substances like green tea extracts and ginger that might help manage inflammation, it’s essential to understand its role in the aging process.

10/ The body runs out of fresh cells

Stem cell exhaustion

Stem cells, fresh and blank, wait for signals to decide their type and function, making them especially useful in replacing damaged cells in our body. These undifferentiated cells can transform into necessary cell types and assist in maintaining our body’s health.

However, senescent cells, old and non-working, emit signals that cause inflammation and can reduce stem cell activity, impacting our immune system and our tissue’s ability to regenerate. Also, issues like the shortening of their telomeres and genetic changes can negatively affect their functionality over time.

11/ Communication between cells loss

Altered intercellular communication

Our cells’ ability to communicate with each other can decline over time, leading to what’s known as altered intercellular communication. Picture it like phones with bad reception, causing misunderstandings between cells. This “static” makes cells send out “SOS” signals when they shouldn’t. These mixed signals can result in inflammation and a weakened immune system, increasing our vulnerability to health issues.

12/ Cells misinterpret instructions

Splicing Dysregulation (new)

Splicing dysregulation is a hallmark of aging that refers to the disruption in how cells process RNA, a molecule vital for translating our genetic code into functional proteins. RNA splicing is like editing a film, where unnecessary clips are removed to create a coherent story. As we age, this “editing” process can become less precise, leading to the production of incorrect or non-functional proteins. These protein anomalies can disrupt cellular functions, contribute to abnormal cell behaviors, and accelerate the aging process. Understanding splicing dysregulation is crucial because it offers insights into age-related diseases and the broader mechanisms of aging.

13/ Decline in cellular cleanup

Compromised autophagy (new)

Compromised autophagy is a hallmark of aging. Think of autophagy as our body’s housekeeping service, responsible for tidying up and recycling damaged cell components. However, as time goes on, this cleanup process becomes less effective. This decline in cellular housekeeping is linked to age-related concerns, including cognitive decline and a less responsive immune system.

Studies have shown that  boosting autophagy can extend the lifespan in mice and enhance the effectiveness of vaccines in older populations by rejuvenating their immune response.

14/ Tissue stiffness increase

Altered mechanical properties (new)

Aging relates to shifts in cells and their surrounding environment. For instance, fibroblast cells change their inner structure as they age, which affects their movement and communication with other cells. These changes, especially in the aging immune system, can damage tissue and harm health. Moreover, the nucleus of a cell, an essential part, changes during aging and can kickstart more cell aging processes. Treatments stabilizing this cell part can extend lifespan in certain conditions that speed up aging. Also, the environment outside of the cell loses flexibility and gets stiffer as we age, leading to various age-related problems and diseases.

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References from the Hallmarks of aging

  1. Low-dose quercetin positively regulates mouse healthspan ž ingling Geng, Zunpeng Liu, Si Wang, Shuhui Sun, Shuai Ma, Xiaoqian Liu, Piu Chan, Liang Sun, Moshi Song, Weiqi Zhang Author Notes Protein & Cell, Volume 10, Issue 10, October 2019, Pages 770–775, https://doi.org/10.1007/s13238-019-0646-8
  2. Quercetin-3-O-glucuronide promotes the proliferation and migration of neural stem cells Author links open overlay panelSamrat Baral a b 1, Ramesh Pariyar a b 1, Jaehyo Kim b c, Ho-Sub Lee b c, Jungwon Seo a b https://pubmed.ncbi.nlm.nih.gov/28110104/
  3. Rapid and selective mobilization of specific stem cell types after consumption of a polyphenol-rich extract from sea buckthorn berries (Hippophae) in healthy human subjects Christian Drapeau,Kathleen F Benson &Gitte S Jensen Pages 253-263 | Published online: 18 Oct 2022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368418/
  4. Quercetin promotes bone marrow mesenchymal stem cell proliferation and osteogenic differentiation through the H19/miR-625-5p axis to activate the Wnt/β-catenin pathway Wei Bian, Shunqiang Xiao, Lei Yang, Jun Chen & Shifang Deng BMC Complementary Medicine and Therapies volume 21, Article number: 243 (2021) https://pubmed.ncbi.nlm.nih.gov/34592982/
  5.  Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development Lindsay Peltz,Jessica Gomez,Maribel Marquez,Frances Alencastro,Negar Atashpanjeh,Tara Quang,Thuy Bach,Yuanxiang Zhao Published: May 16, 2012 https://doi.org/10.1371/journal.pone.0037162
  6. Beneficial action of resveratrol: How and why? Author links open overlay panelGustavo Tomas Diaz-Gerevini Ph.D. a, Gaston Repossi Ph.D. a b c, Alejandro Dain M.D. a, María Cristina Tarres Ph.D. c d, Undurti Narasimha Das M.D., F.A.M.S. e f, Aldo Renato Eynard Ph.D. https://pubmed.ncbi.nlm.nih.gov/32111491/
  7. Determination of Flavonoids from Allium victorialis var. platyphyllum and Their Effect on Gap Junctional Intercellular Communication  https://www.dbpia.co.kr/Journal/articleDetail?nodeId=NODE01728962
  8. Resveratrol counteracts gallic acid-induced down-regulation of gap-junction intercellular communication, Author links open overlay panelJong Hun Kim a b, Bo Kyong Lee b, Ki Won Lee b, Hyong Joo Lee
  9. Inhibition of Gap Junctional Intercellular Communication and Activation of Mitogen-Activated Protein Kinase by Tumor-Promoting Organic Peroxides and Protection by Resveratrol
  10. Targeting strategies for modulating pre-mRNA splicing with small molecules: Recent advances
  1. The Targeting of Noncoding RNAs by Quercetin in Cancer Prevention and Therapy, Man Wang, Xinzhe Chen, Fei Yu, Lei Zhang, Yuan Zhang and Wenguang Chang
  2. Quercetin and Quercetin-Rich Red Onion Extract Alter Pgc-1α Promoter Methylation and Splice Variant Expression
  3. Resveratrol, by Modulating RNA Processing Factor Levels, Can Influence the Alternative Splicing of Pre-mRNAs, M. Andrea Markus,Francine Z. Marques,Brian J. Morris
  4. Regulatory role of resveratrol, a microRNA-controlling compound, in HNRNPA1 expression, which is associated with poor prognosis in breast cancer
  5. The role of autophagy induction in the mechanism of cytoprotective effect of resveratrol
  6. Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability
  7. Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length
  8. The Epigenetic Link between Polyphenols, Aging and Age-Related Diseases
  9. https://www.nature.com/articles/s41392-020-00354-w/
  10. https://pubmed.ncbi.nlm.nih.gov/36040386/
  11. https://www.nature.com/articles/s43587-022-00322-9/
  12. https://onlinelibrary.wiley.com/doi/10.1111/joa.13618/
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