Discoveries Magazine

Cedars-Sinai

Age: A Biological Guide to Longevity

Illustration: Patrick George

Conversations about age tend to go in one of two directions: a gripe about its pitfalls or a fanciful chat that taps into the human longing for immortality. But aging is as fundamental as time itself and, according to a slew of experts at Cedars-Sinai, we would do well to concern ourselves with doing it healthfully (griping optional). So in the interest of demystifying aging and encouraging longevity, Discoveries presents a scientific guide to the force of time on the human organism.

QUESTION
How does brain health affect the rest of the body?

EXPERTS
Dean Sherzai, MD, PhD, and Ayesha Z. Sherzai, MD, Co-directors, Cedars-Sinai Alzheimer’s Disease Prevention Program

WHAT THEY KNOW
Staying agile is key. To care for the brain is to maintain the ability to imbue life with quality and purpose. The brain is a connecting organ: Each neuron can make 20,000 to 30,000 connections with other cells, and evidence shows that healthy agers hang on to more connections in their 80s and beyond. We know that exercise grows the parts of the brain responsible for memory, and that engaging in challenging, novel tasks helps build new connections. Disease development starts early in degenerative conditions such as Alzheimer’s and Parkinson’s, but preventive measures such as good nutrition, exercise, sleep, and stress reduction can preserve brain health.

AND ANOTHER THING
“Sugar is the energy source of the brain, but it should be consumed in slow-release form, as in complex carbohydrates. Pure sugar in your cells is like putting a 1971 Ford Pinto on nitro fuel 24 hours a day. The engine will burn out — the engine in this case being the mitochondria that power the cell.”

Diving Deeper
“Alzheimer’s is probably not a disease that is simply present or absent,” wrote the scientist who started the Nun Study, a landmark effort that began in 1986 examining the lives, diaries, and brains of 678 nuns in Minnesota. One nun, Sister Mary, maintained good cognitive function until her death at 101 years old, despite having a brain stippled with the hallmarks of Alzheimer’s. Various reasons were posited for this, but Dean and Ayesha Sherzai favor one interpretation: “Even with shrunken brains and pathology, Sister Mary and some of the other nuns appeared relatively normal. They had complex vocabularies, as evidenced in their diaries, and were more socially active throughout life. Mental and social activity seem to create connections that confer resilience in the face of significant pathologies that accumulate with aging,” Dean Sherzai says.

QUESTION
Women live a few years longer than men, but do the sexes age differently?

EXPERT
Chrisandra Shufelt, MD, Associate Director, Barbra Streisand Women’s Heart Center at the Cedars-Sinai Heart Institute

WHAT SHE KNOWS
Estrogen influences the whole body. Estrogen plays a key role in almost all tissues and cells; therefore, aging in women is influenced by the decrease of estrogen in menopause. The most well-known effect is bone loss, but the hormonal shift also is linked to increased cardiovascular risk factors such as high blood pressure, high “bad” cholesterol, and low “good” cholesterol. Research on the impact of estrogen on the brain may reveal even more: Withdrawal of estrogen leads to foggy thinking, as in the postpartum period, and may affect women in menopause as well.

AND ANOTHER THING
“My latest research is studying how low estrogen levels affect the immune system and how this, in turn, is connected with heart disease. The data is preliminary, but we have found that lower estrogen levels are associated with higher levels of inflammation in the body, which can lead to disease states, including heart disease.”

QUESTION
Why are older adults more prone to infections?

EXPERT
Moshe Arditi, MD, Executive Vice Chair for Research, Department of Pediatrics; Director, Division of Pediatric Infectious Diseases and Immunology; GUESS?/Fashion Industries Guild Chair in Community Child Health

WHAT HE KNOWS
Testosterone supports immunity. Aging is like infancy in terms of diminished immune function. Vaccine response falls off and the immune system is sapped. One important mechanism, especially in men, is the way testosterone interacts with immune cells. When the hormone dwindles with age, the cells that kill bacteria, viruses, and even cancerous cells are hamstrung. Tumors metastasize more easily and infections can gain a foothold.

AND ANOTHER THING
“As we examine the mechanisms of aging, the goal is to allow people to live more productively. The idea is not to sit at home at 107 years old but to have the mental and physical capacity to write, paint, do science, or some other pursuit. That is what I get excited about.”

QUESTION
Is there any way to reverse aging in older animals?

EXPERT
Helen Goodridge, PhD, Research Scientist, Board of Governors Regenerative Medicine Institute

WHAT SHE KNOWS
Young blood is powerful. Vampiric as it seems, an influx of young blood can reduce some effects of aging in mice. Immune cells produced in the bone marrow are released into the blood where they help maintain all the body’s tissues, so Goodridge gave older mice bone marrow transplants from their youthful counterparts. Sure enough, the transplanted mice exhibited renewed zest and improved memory. Other institutions have performed young-to-old blood and plasma transfusions in rodents and humans, hoping to boost cognitive capacity and even treat Alzheimer’s disease.

AND ANOTHER THING
“The thing that’s attractive about a bone marrow transplant versus a blood transfusion is that, once it’s done, the patient’s blood system is rejuvenated for the long term. There are risks, though, including the need to wipe out the immune system for a time. We are far from recommending bone marrow transplants in older humans, but someday they could be a solution for patients with neurodegenerative conditions.”

QUESTION
What do religions teach us about how to address aging?

EXPERT
Rabbi Jason Weiner, BCC, Senior Rabbi and Manager, Cedars-Sinai Spiritual Care Department and Chaplaincy

WHAT HE KNOWS
Respect your elders. Classical Jewish teachings instruct that a person who is elderly, weak, and dying should be treated as though they are holier than a person in his or her full strength. As the body breaks down, the philosophy goes, one is more in touch with the spiritual aspect of the universe and therefore closer to God. Multiple religions teach the value in wisdom and lived experience, which we should not overlook in a rush to celebrate youth and new ideas.

AND ANOTHER THING
“It can uplift people at the end of life to write an ethical will — a document that describes their values and the knowledge they want to impart to the next generation. It can help ease depression while adding meaning to a life.”

QUESTION
Could regenerative medicine create an elixir of youth?

EXPERT
Clive Svendsen, PhD, Director, Board of Governors Regenerative Medicine Institute; Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine

WHAT HE KNOWS
Eternal youth is foiled by tumors. Scientists can transform an adult skin cell into a stem cell (which can produce new cells of any type) by drenching it in the right chemical cocktail. These cells are called induced pluripotent stem cells. The process also erases damage and returns old cells to mint condition. Theoretically, a doctor could do the same thing to all the cells in a human body. One potential problem is that some of those fresh stem cells would divide like crazy, and some could even become out-of-control growths. The result could be a rejuvenated body riddled by tumors — but the field is trying to find the ideal “tweaking” of the cells to give longevity without tumor formation.

AND ANOTHER THING
“Scientists have rejuvenated mice by reprogramming some of their cells to become stem cells. The researchers at the Salk Institute for Biological Studies didn’t go all the way with this — they just ‘tickled’ the system, if you will. Animals that had a gene that made them age rapidly looked and acted younger and lived longer. In normal mice, some organs performed better after injury. What I would like to see next is evidence that the process can really extend the lifespan of normal mice and also could work in the brain and central nervous system, where cells don’t readily replace themselves.”

Diving Deeper
Late in 2016, an expert on aging published a deduction in Nature that punctured dreams of immortality: The human lifespan may be capped at 115 years. The investigators determined this ceiling by parsing demographics from all over the world. Throughout the 20th century, human life expectancy trended upward, and the very oldest people reached ever-greater ages. In recent decades, these trends have ground to a halt. Regardless of technological innovation and medical advancement, the paper’s lead author is unyielding on the existence of a biological cutoff. The conclusion kicked up a ruckus among scientists, with some vehement disagreement. The debate will go on, but one thing is sure: The death rate is holding steady at 100 percent.

QUESTION
How do individual cells age?

EXPERT
Roberta Gottlieb, MD, Director, Molecular Cardiobiology; Dorothy and E. Phillip Lyon Chair in Molecular Cardiology in honor of Clarence M. Agress, MD; Research Scientist, Heart Institute

WHAT SHE KNOWS
Keep a clean house. An old cell is like grandpa’s garage. It has accumulated a lifetime of odds and ends, and nobody has the energy to identify and sweep away the junk. Body cells accumulate junk such as misfolded proteins, dead organelles (specialized structures), and damaged DNA, which are purged in a process called autophagy. Evidence shows that exercise, caloric restriction, and intermittent fasting are all ways of inducing autophagy and extending health.

AND ANOTHER THING
“I supervised a study at my former organization where we had mice go without food twice per week to trigger autophagy. We kept this going for a full year (until the mice were an elderly 24 months of age) and then studied their immune cells. They were more immunologically youthful and responded better than non-fasting mice to heart attack injury. Even their fur was shinier, which suggests that every tissue in the body responds well to this kind of fasting — at least in rodents.”

QUESTION
How can we ponder our eventual demise in a positive way?

EXPERT
Stuart Finder, PhD, Director, Cedars-Sinai Center for Healthcare Ethics

WHAT HE KNOWS
Change is fundamental. Each stage of aging is preparatory for the next. If a person could avoid all pain in youth — sidestep every pulled muscle and rhinovirus — he might be unfit to cope with serious medical problems in middle and late age. To wipe away the experience of aging would raise fundamental questions about our ability to withstand the struggles of both living and dying. Change over time prepares us to accept change over time. That is life’s great lesson.

AND ANOTHER THING
“Ask yourself: ‘What sort of quality of life have I had, what have I imparted, and what have I embraced? People who are in need, who are in want — how do I help them?’ Every footprint I leave, I am changing the world. That is something that should concern me, whether I’m 20 years old or 90 years old.”

QUESTION
Why does hearing fade with age?

EXPERT
Martin L. Hopp, MD, PhD, Medical Director, Cedars-Sinai Sinus Center; Otolaryngologist, Head and Neck Cancer Center and the Division of Otolaryngology

WHAT HE KNOWS
Decay happens. We all lose hearing over time because noise wears out the hair cells in the ear — large noises such as explosions can destroy them quickly. People exposed to more noise over time, even low-key city noise, will lose hearing faster than those in serene environments. The impact is serious because hearing loss has been linked to accelerated brain shrinkage and dementia.

AND ANOTHER THING
“The little hair cells in the ear can recover from loud sounds like concerts if exposed for less than one hour at a time.”

QUESTION
What can we do to help people age healthily in their homes?

EXPERT
Harriet Aronow, PhD, Research Scientist, Nursing Research

WHAT SHE KNOWS
It takes a village to age well. In decades of caring for older adults and leading research into their challenges, Aronow has determined that the most valuable asset for this population might be community. Most people will fight to hang on to independence at all costs, so a balance must be struck between autonomy and cooperation with caregivers, service providers, and family members. For example, a person might have to curtail or give up driving and therefore become isolated. Hiring a rideshare or taxi could solve the problem, but first the older adult must be willing to accept help.

AND ANOTHER THING
“One solution — growing in use as the population ages in place — is the NORC: naturally occurring retirement community. An organization emerges in an existing neighborhood with many older adults. It arranges or provides services to the community like transportation and nutrition. It creates a central node that tracks people’s needs — and meets them.”

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