Part 1 of 2 – DNA Methylation Associated With Disease and Aging

DNA methylation is very important in aging solutions.

DNA methylation is becoming recognized as a being associated with specific diseases, and also resulting in age related decline.

Its measurement is used as an important aging biomarker.

DNA methylation step-by-step — starting with the basics so non-scientists, and scientists working in different disciplines, can better understand this:

  • DNA consists of sequences of the molecules adenine, cytosine, guanine, thymine (represented as A, C, G, and T)
  • CpG sites are DNA segments consisting of cytosine, followed by guanine. The “p” means “followed by”.
  • So CpG = “C followed by G”.
  • A methyl group is a specific type of molecule. Things like diet and toxins affect the creation of methyl groups.
  • Methylation is when a methyl group becomes added to a CpG site
  • Methylation typically acts to repress (turn off) gene transcription, although it can trigger transcription and have other effects
  • It does this without changing the DNA sequence
  • Some CpG sites should be methylated for good health, and human development is partly controlled by changing methylation over time.
  • Methyl groups attached to a combination of specific CpG sites is called a methylation pattern.
  • There is a DNA methylation pattern associated with youth.
  • As we grow older, more CpG sites become methylated, so more genes are repressed (or there are other effects to DNA sequence) resulting in the negative effects of aging.
  • Measuring the epigenetic clock is measuring methylation patterns to arrive at an individual’s biological age.
  • Methylation at specific CpG sites are associated with specific diseases. So it’s a small step to see how methylation at specific sites can be associated with the effects, infirmaries and decline of aging – some or all of the following:
    • Reduced strength, energy, and passion for life
    • Faded appearance, aching bones, loss of productivity, decreased sex drive, declining memory, thinning grey hair, sagging skin
    • Just plain feeling bad
    • etc
  • Research is underway to understand the molecular pathways of different therapies resulting in resetting the epigenetic clock to a more youthful pattern.

Next I’ll send more references, including references about the association of methylation with specific components and therapies — rapamycin, senolytics, telomeres etc.

And will try to get some specific CpG sites associated with specific diseases and the effects of aging.



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Gene Editing Trials Poised to Expand, but Hurdles Remain

Medscape Medical News
Ricki Lewis, PhD
November 30, 2015

Article Highlights:

  • So far, few formal gene editing clinical trials are in progress
  • but improvements in the technology are expected to accelerate
  • Gene editing uses DNA-cutting enzymes, called nucleases, to remove, alter, or replace specific DNA sequences
  • Clinicians made headlines worldwide with the case of Layla Richards, the 1-year-old girl who was treated for aggressive acute lymphoblastic leukemia (ALL)
  • Cellectis is funding clinical trials to test chimeric antigen receptor cells in larger groups of patients with ALL
  • The T cells that Layla received were novel in two ways:
    • they were the first cells engineered using the gene-editing tool transcription activator-like effector nucleases (TALENs),
    • and the first to use gene-edited donor cells, which opens the possibility of “off-the-shelf” products

Looking forward to applying gene editing to slow and ultimately reverse aspects of age related functional decline.

Full article:

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There must be something substantially different in young blood compared to old

Andrew Johnson and team at National Institute of Health/National Heart, Lung and Blood Institute believe there must be something substantially different in young blood compared to old.   They conducted an extensive study using thousands of patient blood samples that was then replicated.

The study identified 1,497 genes in blood cells and/or brain tissue that showed significantly differential expression patterns in older individuals when compared to younger individuals.

  • They had analyzed the blood samples transcriptome, a measurement of the RNA transcripts from each gene.  The compilation of RNA transcripts is a reflection of the relative expression levels of the genome at a given point in time.
  • They chose the transcriptome (the set of all RNA molecules, including mRNA, rRNA, tRNA, and other non-coding RNA transcribed in one cell or a population of cells), as all the cells in an organism will have the same DNA and this DNA does not generally change during the person’s lifetime, thus making DNA genomic analysis less useful for an age-related study.
  • What does change over a person’s lifetime is modifications of DNA, which genes are expressed from the DNA and the relative levels of expression of each gene.
  • This study was published in Nature Communications.  It used blood cells and brain tissue to examine age-associated changes in gene expression.
  • Gene expression can either be negatively or positively expressed at a lower or higher level in relation to chronological age.
  • Three distinct groups of genes were negatively correlated with chronological age.
  • An interesting finding in this study involved epigenetic patterns, specifically methylation on cytosines.
  • Epigenetics doesn’t change the underlying pattern of DNA base pairs, but instructs how a gene is to be expressed.
  • The 1,497 genes identified as being associated with chronological age offer a plethora of new targets to better understand the aging process and age-related diseases.
  • With current progress in gene therapy and drug fields it’s possible that some of these 1,497 genes could potentially be manipulated to ameliorate many age-related diseases.

Full articles

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AGINGSCIENCES™ – Anti-Aging Firewalls™ has posted a new item, ‘G-qaudruplexes’

Just a few highlights, best to read it all

– G-quadruplexes are secondary semi-stable folded structures found in our DNA and RNA which tend to assemble around guanine-rich sequences in the presence of cation molecules like potassium.

– The article and images show how G-complexes make DNA look a lot more complicated than “prevailing dogma” (simple guanine/cytosine base pairs) shows.

– G-quadruplexes are an alternative way that DNA and RNA can fold – and adopt a variety of geometric configurations depending on where they are found.

– They’re very relevant to many critical biological processes like gene regulation, expression of telomerase and telomere maintenance, understanding of growth/oncogenes like C-myc, understanding of organismic development, comprehension of certain enigmatic diseases like ALS and possible new cancer treatments.

– Many critical aging-related processes like the telomere/telomerase story can’t be fully told without considering G-quadruplexes.

– G-quadraplexes are only one of several types of quadraplex structures

– Article continues in detail. It’s a recommended read.

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Aging 2.0 group

Dear GRG Member,

Aging 2.0 about page says
Aging2.0® is a global innovation platform for aging and senior care. It is on a mission to accelerate innovation to improve the lives of older adults around the world. (continues)

Looks like a useful group. You can sign up for their newsletter on main page

Upcoming expo Nov 19-20

Events have product presentations and networking. Leadership team are key members of sister group Generator Ventures. Good to harness free enterprise to advance creation of aging solutions.

They have “Pitch Events”. Look for others
#30in30in30 is an initiative supported by Aging2.0 to encourage local communities around the world to host pitch events for new innovative products and services that stand to improve the lives of older adults. We are taking part by hosting one of 30 Pitch Events in 30 cities around the world in 30 days.


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Quantification of biological aging in young adults

Quantification of biological aging in young adults

Biomarkers measuring results

Numerous blood measures: starts at “Pace of Aging”
Glycated hemoglobin, forced expiratory volume in one second (FEV1) and others
Physical Limitations
Cognitive Testing
Retinal Imaging
Self Rated Health
Facial Aging

Young People Age at Different Rates
Kristie Nybo, PhD

A newly developed method for measuring aging during youth confirmed that some people age quicker than others.

Logically, it seems that one year in time should add one year of wear and tear to your body. But some years seem harder on us than others and some people maintain their baby faces long after their same-age peers develop wrinkles. Now in the journal Proceedings of the National Academy of Sciences, researchers present a new method to measure the rate of aging in young people and used it to confirm the suspicion that people age at different rates.

To develop the new approach, Israel’s team turned to the Dunedin Study, a collection of 1037 individuals monitored from birth until age 38 for 18 biomarkers established as risk factors for chronic disease. The team assessed indicators of the health of the cardiovascular, metabolic, and immune systems, as well as kidney, liver, and lung functions, dental health, and DNA features such as telomere length.

Although none of the study participants showed evidence of age-related disease, test results indicated that the 38 year old study participants ranged from 28 to 61 years old biologically. By using measurements from ages 26, 32, and 38, the team quantified each study participant’s rate of physiological deterioration and found that some participants showed nearly 3 years of physiological change per chronological year, while others showed almost no change at all.

The researchers found that biomarker evidence of advanced biological age correlated with poor performance on balance and motor tests, reduced muscle strength, and poor cognitive functioning. These individuals also looked older to undergraduate students estimating the age of individuals in photos.

“This research shows that age-related decline is already happening in young adults who are decades away from developing age-related diseases, and that we can measure it,” Israel said.

Interestingly, three study participants’ biomarkers indicated that they were growing healthier or younger during their 30s.

“Above all, measures of aging in young humans allow for testing the effectiveness of antiaging therapies (e.g., caloric restriction) without waiting for participants to complete their lifespans.”


Belsky DW, Caspi A, Houts R, Cohen HJ, Corcoran DL, Danese A, Harrington H, Israel S, Levine ME, Schaefer JD, Sugden K, Williams B, Yashin AI, Poulton R, Moffitt TE. Quantification of biological aging in young adults. Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):E4104-10.

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NIA advisory: Can We Prevent Aging?

NIA advisory: Can We Prevent Aging?

Excerpt from National Institute of Aging article — link is below:

The National Institute on Aging (NIA) investigates ways to support healthy aging and prevent or delay the onset of age-related disease and decline. We have already gained important insights, and what we learn from ongoing and future studies may not only help to increase longevity, but may also promote what is known as “active life expectancy”—the time in late life free of disability. We already know, for example, that healthy eating and exercise and physical activity help promote healthy aging. Are there other interventions that can help? NIA-supported and other studies are taking a look at the possible benefits and risks of a number of approaches, including antioxidants, calorie restriction, and hormone supplements. This tip sheet provides an overview of what we know about these interventions and the research needed to learn more. Until we have a better understanding, it is a good idea to be skeptical of claims that any supplements can solve your age-related problems.

Calorie restriction
How Hormones Work
Hormone Therapy
Some Dangers of Hormone Therapy and “Anti-Aging” Supplements
Human Growth Hormone
Hormones in Women
Many Questions, Seeking Answers

Article on the NIA web site:

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