p53 , resveratrol , pancreatic cancer and apoptosis

Intrigued by pancreatic cancer, infection and environmental toxins, I stumble into this topic from Wiki. One of my clients died of stomach , esophagal and pancreatic cancer. Previous to that , he had shingles and other infections.  Her immune system became weaker during the last 5 years before his death.  He disregarded stomach pains and […]

Novel Type of Cell Death in Huntington’s Disease May Lead to Effective New Therapies

Summary: Researchers have identified a novel type of cell death associated with Huntington’s disease. Source: Tokyo Medical and Dental University. Researchers centered at Tokyo Medical and Dental University (TMDU) identify novel type of cell death in Huntington’s disease that may uncover new treatments. In Huntington’s disease (HD), the huntingtin gene is mutated, causing progressive neuronal […]

Causal Link Between Alzheimer’s Disease and Telomere Shortening

In a newly published study, researchers at Karolinska Institutet show that the shortening of the telomeres – the caps at each end of the chromosomes in our cells – can be linked statistically to the active mechanism responsible for Alzheimer’s disease. However, the effect is small and telomere length cannot yet be used to assess […]

What is your molecular age? P16 protein can ID your molecular age

Aging biomarket test –  coming soon

Researchers report the development of a new blood test that they say may show your “molecular age,” as opposed to your chronological age.

That test measures levels of a protein called p16. A new study shows that p16 levels rise as people age, that smokers have higher levels of p16 than nonsmokers, and that people who exercise have lower levels of p16.

The test isn’t available to the public yet. But if it was, would you want to know your “molecular age”?

Let’s say you took the test and found out your molecular age was greater than your chronological age, suggesting that your aging process is on the fast track. Or maybe you’d find out that the opposite is true, that your clock isn’t ticking quite as fast as you thought.

What would you do with that information? Would it spur you to make lifestyle changes to try to stave off aging, or would you be looking for reassurance that your healthy habits are paying off?

Role in senescence

Concentrations of p16INK4a increase dramatically as tissue ages. p16INK4a, along with senescence-associated beta-galactosidase, is regarded to be a biomarker of cellular senescence.[32] Therefore, p16INK4a could potentially be used as a blood test that measures how fast the body’s tissues are aging at a molecular level.[33]

It has been used as a target to delay some aging changes in mice. P16 along with SABG can be a biomarker of cellular senescence.

Senescence-associated beta-galactosidase (SA-β-gal or SABG) is a hypothetical hydrolase enzyme that catalyzes the hydrolysis of β-galactosidesinto monosaccharides only in senescent cells. Senescence-associated beta-galactosidase, along with p16Ink4A, is regarded to be a biomarker of cellular senescence.[1]

Its existence was proposed in 1995 by Dimri et al.[2] following the observation that when beta-galactosidase assays were carried out at pH 6.0, only cells in senescence state develop staining. They proposed a cytochemical assay based on production of a blue-dyed precipitate that results from the cleavage of the chromogenic substrate X-Gal. Since then, even more specific quantitative assays were developed for its detection at pH 6.0.[3][4][5]

Today this phenomenon is explained by the overexpression and accumulation of the endogenous lysosomal beta-galactosidase specifically in senescent cells.[6] Its expression is not required for senescence. However, it remains as the most widely used biomarker for senescent and aging cells, because it is easy to detect and reliable both in situ and in vitro.

P16 Role in cancer

Mutations resulting in deletion or reduction of function of the CDKN2A gene are associated with increased risk of a wide range of cancers and alterations of the gene are frequently seen in cancer cell lines.[13][14] Examples include:

Pancreatic adenocarcinoma is often associated with mutations in the CDKN2A gene.[15][16][17]

Carriers of germline mutations in CDKN2A have besides their high risks of melanoma also increased risks of pancreatic, lung, laryngeal and oropharyngeal cancers and tobacco smoking exacerbates carriers’ susceptibility for such non-melanoma cancers.[18]

Homozygous deletion of p16 are frequently found in esophageal cancer and gastric cancer cell lines.[19]

Germline mutations in CDKN2A are associated with an increased susceptibility to develop skin cancer.[20]

Hypermethylation of tumor suppressor genes has been implicated in various cancers. In 2013, a meta-analysis of 39 articles using analysis cancer tissues and 7 articles using blood samples, revealed an increased frequency of DNA methylation of p16 gene in esophageal cancer. As the degree of tumor differentiation increased, so did the frequency of DNA methylation.

Tissue samples of primary oral squamous cell carcinoma (OSCC) display hypermethylation in the promoter regions of p16. Cancer cells show a significant increase in the accumulation of methylation in CpG islands in the promoter region of p16. This epigenetic change leads to the loss of tumor suppressor gene function through two possible mechanisms. Methylation can physically inhibit the transcription of the gene or methylation can lead to the recruitment of transcription factors that repress transcription. Both mechanisms lead to the same end result—downregulation of gene expression that leads to decreased levels of the p16 protein. It has been suggested that this process is responsible for the development of various forms of cancer serving as an alternative process to gene deletion or mutation.[21][22][23][24][25][26]

Clinical use

Use as a biomarker

Furthermore, p16 is now being explored as a prognostic biomarker for a number of cancers. For patients with oropharyngeal squamous cell carcinoma, using immunohistochemistry to detect the presence of the p16 biomarker has been shown to be the strongest indicator of disease course. Presence of the biomarker is associated with a more favorable prognosis as measured by cancer-specific survival (CSS), recurrence-free survival (RFS), locoregional control (LRC), as well as other measurements. The appearance of hyper methylation of p16 is also being evaluated as a potential prognostic biomarker for prostate cancer.[27][28][29]

p16 FISH

p16 deletion detected by FISH in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma.[30]

p16 immunochemistry

Gynecologic cancers

p16 is a widely used immunohistochemical marker in gynecologic pathology. Strong and diffuse cytoplasmic and nuclear expression of p16 in squamous cell carcinomas (SCC) of the female genital tract is strongly associated with high-risk human papilloma virus (HPV) infection and neoplasms of cervical origin. The majority of SCCs of uterine cervix express p16. However, p16 can be expressed in other neoplasms and in several normal human tissues.[31]

Urinary bladder SCCs

More than a third of urinary bladder SCCs express p16. SCCs of urinary bladder express p16 independent of gender. p16 immunohistochemical expression alone cannot be used to discriminate between SCCs arising from uterine cervix versus urinary bladder.[31]

Email motherhealth@gmail.com if you want more info on testing your molecular age next year as we will add this service at avatarcare.net  soon.


P16 (gene) has been shown to interact with:

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Exercise your brain with cross-fit training

It’s been three months with a crossfit training coach at NC Fit when my coach asked me why I attend my 30min group training every day. I told my coach Brandon, that I wanted to increase 10 yrs in my life. I want to help raise my future grandchildren and be able to experience life everyday and share it with others.

http://nc.fit/memberships

Mention my name (Connie Dello Buono) when joining this cross fit gym in the bay area. My team asked what I eat for breakfast and I said one pouched egg and Roibois tea. I also use VEGA protein powder and Garden of Life after working out. My mom cooks fish and veggie for me and my friend shares his garden produce with me.

I want to be a good example for my children and hopefully I will not spend any fortune when it is time for me to be taken cared for during old age.

I worked two jobs, sending my children to college and some nieces in the Philippines to college. I have a fitness and financial goals.

NC Fit cross fit.JPG