Pushing off the Inevitable: Research Resisting Mortality

It seems that every time I dare turn on the T.V. I am involuntarily scarred by commercials of old men craving a sex drive. It makes you wonder...are Americans increasingly obsessed with youth? Or is the market simply appealing to the aging baby boomers? Whatever the reason, I'm here to discuss some of the research going down on anti-aging.

past century has seen a 30 year increase in the average American lifespan. Scientists attribute this dramatic, 140% rise to cooperative measures taken to control infectious disease, improve sanitation, and promote the use of antibiotics and vaccines. However, there is a limit to the number of years these measures can add to the average lifespan, which has now steadied at 77 years in the U.S.

If not external environmental factors (i.e sanitation), then what other factors limit our lifespan? Turns out, the answer is within. Scientists are increasingly examining internal factors - genetics, immunology, cell biology, neurology, and microbiology - to understand the secrets of long life.

With billions now flowing into anti-aging research, I will briefly summarize  some of the prominent advances in hormone therapy, gene mutation, and drug therapy as they relate to the quest to extend life.

Hormones Therapy

"Finding a 'fountain of youth' is a captivating story," says the National Institute on Aging. "The truth is that, to date, no research has shown that hormone replacement drugs add years to life or prevent age-related frailty."

Accordingly, the FDA has not approved hormone replacement drugs for combating aging. 

And yet, hormone replacement pharmaceuticals staunchly continue to support a booming, one-billion dollar industry – and customers are willing to pay high prices. A hormone based dietary supplement known as DHEA (dehydroepiandrosterone), which the body converts into estrogen and testosterone, sells at $12.95 for a single capsule. 

There exists a deep divide in confidence of hormone replacement therapies between pessimistic scientists and optimistic doctors and patients. The truth is that there have been no long term clinical research conducted on many hormone drugs, including DHEA.

Patients seem to use the simple logic that since hormone levels are highest in youth, added hormones in old age will increase youthful energy and strength. In reality, the body remains a delicate balance in hormone levels that can fluctuate every hour to maintain stability. Hormone therapies disrupt this natural, healthy variation.

Human growth hormone (HGH) can be especially dangerous, with studies even suggesting that people with naturally high levels of growth hormone die at younger ages than those with lower levels of the hormone (Read Hanneke Hop's experience with HGH shots).

 Read more on Hormone Therapy:

Overall discussion on aging with emphasis on hormones

A discussion of HGH

Gene Mutation

 

C. elegans, a microscopic round worm...
he's kinda cute

Studies have shown that genes attribute to 25% of  the variation in the human life span. 

Dr. Cynthia Kenyon, director of the Hillblom Center for the Biology of Aging at the University of California, San Francisco has identified daf-2, a gene thought to play a major role in aging. 

Kenyon used the model organism, Caenorhabditis elegans, because of its simple physiology and short lifespan of just two to three weeks. She found that when the daf-2 gene was mutated, the roundworms lived twice as long. 

In a later study, researchers led by Gary Ruykun, found that daf -2 codes for the creatively named  DAF-2 protein, which acts similarly to the human insulin receptor proteins. 

Further research found that single daf-2 gene actually controls the expression of a whole slew of genes through a cascade of events. Daf-2 reduces the expression of daf-16 (via phosphorylation),  a gene that encodes a transcription factor and thus regulates hundreds of other genes. In concert, this cassette of genes regulate a variety of physiological processes including: metabolism, fertility, stress response, collagen levels,and cell growth.  

Thus, daf-16 is crucial to life extension and healthy aging, and mutating its suppressor, daf-2 could extend life. 

If daf-2 limits lifespan, than why has the gene and its corresponding insulin pathway passed the test of evolution? Would it not be unwise to ignore what evolution has determined to be fit for survival? 

It turns out that daf-2 is vital; dysregulation of our insulin pathway and natural aging processes (slow of cell growth, fertility, and metabolism) can lead to both Type II diabetes and cancer, two diseases that increase with age. 

I suppose that evolution has decided that it is best to die younger, free of disease than to live longer and be crippled by these debilitating ailments. Would you agree?

Read more on gene mutation:

Summary of UCSC anti-aging symposium featuring Dr. Kenyon's research

Successful gene therapy in mice

Describes genetic control of aging 

General article on various target aging genes

Drug Therapy

If I were to discuss just one anti-aging drug, it would be resveratrol. It is a chemical that is found in small quantities in red wine, but it is now being produced synthetically for stronger, more concentrated activity. 

It all has to do with calorie restriction. Calorie restriction is the only well established factor to increased lifespan.  Calorie restriction, in its role in inducing metabolic changes, improvement of insulin sensitivity, and regulation of neuroendocrine function, has been shown to reduce diabetes, cancer, cardiovascular disorders, and other age-related ailments. 

So where does resvertarol come into play? It turns out that this chemical naturally mimics calorie restriction by enhancing the expression of the key enzyme, SIRT1. Mechanisms in which it does so are unclear, but it proves to be a promising field of study. 

What implications do you think exist when our bodies reap the benefits of calorie restriction without actually restricting calories?

Why Reading Fast is Overrated

Saturday Mornings were then Torturous.

Mother would have her day off. She would use this day to Discipline Us. 

1 hour Math Tutoring

1 hour Science Studying

1 hour Read Aloud

Repeated for her Four Children, each one dreading the end of the former's session - signaled by mother's Shrill Calling voice that she saved Just for Us, so we could not reasonably pretend to have not heard.

The Read Aloud session was Most Painstaking. Over the course of an hour, we would read perhaps just five to ten pages. Reading for Content, but more importantly, Reading for Language. And never, never for speed.

She would have us read a sentence, then she would repeat it, emphasizing each noun and each verb. And what did they mean? We weren't sure. So we would write down the "juicy" words and sentences in a notebook, define them, memorize them, appreciate them. We would learn.

Growing up in Pakistan, Mother was one of 8 children. 

Aware of surrounding poverty and illiteracy, and aware of her comparatively privileged life, she would never let knowledge to pass her without absorbing and analyzing its every aspect. Still, she takes incredible value in every word, every sentence, studying the infinite beauty in which authors seamlessly connect each idea to one cogent whole. She reads.  She re-reads. She writes. She re-reads the written. She memorizes, appreciates, learns, and connects. 

In this day and age, information is ubiquitous and infinitely more available than it was during my  mother's day and age. With all this information, more things slip than stick, enslaving our God-given drive for depth and meaning to the allure of More, Faster.

As a precursor to the science journalism that I will attempt in my upcoming posts, this post delineates some of my underlying goals of this blog - dedication, depth, and deliberation.

Maybe this blog is just a pathetic attempt to one day reach just half the level of depth that my mother has achieved. 

Time will Tell.

My First Research Project

Before my freshmen year of college, Clarkson University took on the expensive venture of letting me research under a faculty mentor. That's right - before I took any introductory science courses or labs. While I of course didn't make any big discoveries, it was a deeply maturing, humbling, and inspiring experience. 

I'm going to now kill two birds with one stone. 1) Proper abstract format and 2) attempt to elucidate you on the details of my research. If you don't care about these two things (and I wouldn't blame you), just skip ahead. 

Here is the abstract of my research:

The Estrogen-Receptor Responsiveness in Various Cervical Epithelial Cell Lines

Name, Faculty Mentor(s)

Department of Biology, Clarkson University, Potsdam, NY

                                                 

The major risk factor associated with cervical cancer is infection with high-risk strains of human papillomaviruses (HPV). HPV16 and 18 alone cause 70% of cancers attributable to HPV. However, HPV resolves spontaneously in 80 – 90% of cases; the low frequency of persisting infections suggests that HPV alone does not lead to cervical cancer. Scientists believe that non-viral cofactors, such as estrogen, must also contribute to the onset of cancer. The uterine cervix is highly responsive to estrogen and recent studies suggest that estrogen and its receptor, ERα, in combination with HPV oncogenes, contribute to carcinogenesis by inducing cell proliferation. We are measuring and comparing the estrogen responsiveness of cultured HPV16-immortalized, tumor, and normal cervical epithelial cell lines. Cells are transfected with a reporter gene containing the estrogen response element (ERE) attached to the firefly luciferase gene. The cells are treated with varying dosages of estradiol and the estrogen activity is determined using the dual luciferase assay. Overall, our findings support high estrogen sensitivity in normal cells and low responsiveness in tumor lines. We will use this data to determine the optimal dosage and duration of exposure to fulvestrant, an estrogen receptor inhibitor, as a treatment of HPV-infected cells.

I’d like to acknowledge and thank the National Institutes of Health (NIH) for their support and funding, and for the resources and knowledge provided by our mentor, Dr. Craig Woodworth.

*DISCLAIMER* - It took me about 10 research articles to be able to understand what I was writing - so don't worry!

What I Learned from my First Research Project

1) Death Trap of Idealism

When students first enter STEM fields and consider the concept of "researching" they often enter a false notion of optimism. For the biochemistry student, she will find a cure for cancer; the evolutionary biology student will discover a new species; the engineer will build a cost-effective clean water delivering system for  third world countries. These are fine life goals to have, but as an undergraduate researcher your main goal is to master techniques. Little else (unless you are a junior or senior) is expected of you.

2.) Reading 

Thanks to my thoughtful mentors, any idealistic dreams that might have budded inside of me were smothered under the humbling load of dense academic papers that I was told to read. Reading these can be utterly DRAINING and understanding one article might take close to 100 Google searches to clarify terms and concepts. My advice - save the reading for home! If you read in between experiments you will likely be too tired to concentrate on your experiment.  Also, if you aren't already a coffee or tea drinker, become one.

3.) Don't Run into Dead Ends

So you made a hypothesis and you want so desperately for your data to support it. You construe the data or represent it in a way to best serve your interests. Don't fall into this

trap! If you have done enough trials, and it is clear that your data doesn't support your hypothesis, it's okay! An unsupported hypothesis often opens up new horizons of scientific possibilities and explanations. Research is all about critical thinking. Use the articles you have read to help clarify the meaning of your results and create a new hypothesis. When you reach a dead end, build new roads. 


For More Tips on Research, visit:  US News 8 Tips for the College Researcher