Thinning and graying hair, wrinkles, arthritis, cataracts, heart disease, diabetes, cancer, and maybe dementia. The list of age-related maladies is both familiar and intimidating.

On the microscopic level, cells also show characteristic signs of aging. They become loaded with debris. The neatly packaged bundles of DNA lose organization. Telomeres, the protective caps of chromosomes that guard DNA, wear down. Stem cells, which replace destroyed cells throughout the body, lose their regenerative capacity.

These changes are linked, so anything that affects cellular deterioration shows up in the whole body. And for millennia, these changes were considered irreversible and inevitable, ending in death.

While eternal youth remains firmly in the realm of science fiction, there’s now solid scientific evidence that the inevitable aging process is not so inevitable after all. Methods of slowing down aging are available right now.


Moreover, some of these anti-aging methods are free and can be applied by anyone. They can be as simple as changing the way you think about the problems and opportunities of life. Some of the classic health advice, such as exercise and refraining from smoking, also plays a role.

And in the more distant future, scientists envision developing therapies to reverse the cellular marks of wear and tear, restore telomeres, remove damaged cells and replace them with healthier cells.

Much of this anti-aging research is being carried on in the laboratories of San Diego area researchers and biotech companies. This includes:

-- Healthy elderly ages 85 and up and their DNA are being examined in the Wellderly Study by Scripps Health, led by Dr. Eric Topol. Volunteers are still being sought, go to j.mp/wellderly for details.


-- Human Longevity, a company co-founded by genome pioneer J. Craig Venter, is performing large-scale DNA sequencing to find health-related variants.

-- The Salk Institute hosts noted researchers studying aging, including Juan Carlos Izpisúa Belmonte and Jan Karlseder, who have made major advances in the field.

A groundbreaking study led by Izpisúa Belmonte and published Thursday demonstrated that signs of aging can actually be reversed, in mice, by intermittent production of four proteins that reprogram cells back to an embryonic-like state when continuously produced.

Karlseder found in another recent study that artificially lengthening telomeres makes them unstable, damaging cells. This means that telomere lengthening can’t be considered a surefire solution to aging.


Extending health

While life extension may be a byproduct of some of this research, it’s not necessarily their goal, said Felipe Sierra, director of the Division of Aging Biology at the National Institute on Aging. In a word, they’re trying to extend the “healthspan,” that period of life in which people enjoy good health.

“The goal is not to live to 150,” Sierra said. “The goal is to live to 150 in good health. When you ask people, would you like to live to 150, most people say, I’m going to get sick around 70 and then I’m going to be miserable for 70 or more years. No, I don’t want that.

“However, if you asked them, do you want to live to be 150 and be healthy until you’re 140, then the answer is different.”


Life expectancy has traditionally been a key public health metric because it’s binary and objective, Sierra said — you’re either alive or dead. Moreover, the assumption has been that improving lifespan implies reducing disease.

But the actual experience for many people has been that extending their lives means they spend their added years in an unhealthy and unhappy state, Sierra said. So the goal of researchers now is to delay and treat the onset of serious diseases and disabilities.

“We usually think of the diseases that kill us, cancer, cardiovascular disease and so on,” Sierra said. “But personally, I think more important are the diseases that rob us of our quality of life, like arthritis, hearing problems vision problems. If I cannot move my fingers, I cannot paint, I cannot play the guitar; I’ll be very unhappy.”

Diseases have historically been treated individually. With the advance in understanding aging, it’s now realistic to envision combat aging itself, Sierra said. If aging is inhibited, so will age-related diseases.


Metformin, the widely used diabetes drug, has emerged as one potential anti-aging drug. Experiments in rodents indicate the drug alleviates age-related conditions, such as inflammation, oxidative damage and cell senescence that promote disease.

Since metformin was approved decades ago, its safety profile is well-understood. That should speed up getting a clinical trial under way; one is now being prepared but is not yet accepting applicants. More information can be found at: j.mp/metforminaging.

If metformin does indeed delay the onset of any diseases, it would improve quality of life, even if the actual lifespan doesn’t increase, Sierra said.

Controlling stress


“A merry heart doeth good like a medicine: but a broken spirit drieth the bones.” — Proverbs 17-22, King James Version

As the proverb above indicates, the idea that one’s outlook on life influences health is thousands of years old. But only in recent years has direct scientific evidence emerged to show not only that this folk wisdom is true, but how it operates at the cellular level.

Elizabeth Blackburn, president of the Salk Institute for Biological Studies, has coauthored an entire book explaining how people can influence their aging process to improve health and be happier in the process.

Blackburn shared a Nobel Prize in 2009 for her discovery of telomerase, an enzyme that restores telomeres.


The book, “The Telomere Effect,” is based on discoveries about how chronic stress, poor diet and lack of good sleep accelerates loss of telomeres, the protective caps of chromosomes. It will be available Jan. 3, 2017. Go to j.mp/telomerebook for more information.

Each time a cell divides, its telomeres shorten. Eventually, they become so short that cells stop dividing and become senescent. This prevents production of cells that can become genetically unstable and lead to cancer (telomerase is activated in most cancers). But stress can trigger telomere loss prematurely.

Blackburn and coauthor Elissa Epel describe in detail the research that found the association between aging, telomere reduction and stress, along with further evidence that this association is causal.

“Genetics has been very helpful in showing there are real causality effects,” Blackburn said. “For most of us, you really can modulate this.”


Psychological habits such as training to focus one’s attention, avoiding habitual pessimism, reducing stress-inducing things in life that are within your control and cultivating a few close friendships can help, the authors recommend. Good sleep patterns and exercise (which go together), along with avoidance of sugar and refined carbohydrates also help maintain telomere length.

“It’s not the only one,” Blackburn said. “It interacts with all the other things in our lives … but it’s one part of (aging) that’s important in humans, because we live so many decades that small things can accumulate and have big effects if they go on long enough.”

Izpisúa Belmonte, the Salk Institute stem cell researcher, has explored how aging decreases the body’s regenerative ability, Blackburn said.

“The telomere aspect converges on the same thing,” Blackburn said. “Telomeres run down in our stem cells, and then the stem cells won’t replenish tissues.”


Looking ahead

The Izpisúa Belmonte-led study will most immediately be useful for providing a model platform for controlling and studying aging in animals, said Amy Firth, a stem cell researcher at the University of Southern California.

“The strategy they’ve used provides a fantastic tool to learn the complexity and gain mechanistic insight into aging,” said Firth, assistant professor of medicine at the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC.

With aging reversal, scientists can now study the molecular mechanisms and pathways involved in aging, and validate what is now thought to drive aging, and to find new targets, Firth said.


“You’ve got it at a cellular level, at a tissue level, at a whole organ level, and now the whole animal level,” Firth said. They can do anything from single-cell analysis to whole animal analysis now.”

With that knowledge, she said, scientists and medicinal chemists can close in on the ultimate prize — therapies to target these mechanisms.

When that takes place, aging will present a new face to humanity. Instead of an inevitable reminder of our mortality, aging will become just another disease to be treated and eventually cured.

bradley.fikes@sduniontribune.com


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