21st Century Science

Human Longevity Science: Healthy Births and Aging

Epigenetic Aging Biomarkers of Mild Cognitive Impairment, Alzheimer’s Disease and Related Dementias, and Brain Aging

In the United States, 1 in 3 seniors dies with Alzheimer’s or another dementia, and more than 6 million Americans are living with the disease, according to the Alzheimer’s Association. Alzheimer’s disease kills more people than breast cancer and prostate cancer combined.

“If we can slow biological aging, we may be able to prevent multiple diseases and conditions that affect older adults simultaneously. My work is a step toward understanding whether epigenetic age acceleration is a biomarker of biological aging that can predict future risk of Alzheimer’s disease and related dementias,” said Aladdin H. Shadyab, Ph.D., assistant professor at the Herbert Wertheim School of Public Health.

“We will investigate whether epigenetic age acceleration is associated with higher risk of Alzheimer’s disease, with the long-term goal of determining whether targeting epigenetic aging could slow or prevent the development of Alzheimer’s disease. We also want to identify age-associated epigenetic mechanisms of dementia as possible therapeutic targets,” said Shadyab, whose work is at the intersection of geroscience, longevity science and multiomics.

Chronological age is based on a person’s birthdate. Epigenetic aging refers to the biological age of a person’s cells, tissues and organ systems. If biological aging occurs faster than an individual’s chronological age, the person is undergoing epigenetic age acceleration, which is associated with higher risk of cancer, cardiovascular disease, Parkinson’s disease, and other diseases.

Research on the role of epigenetic aging on cognitive and brain health is limited. Shadyab and colleagues have added to data with research published in peer-reviewed journals like the August 2021 paper identifying an association with epigenetic age acceleration and cognitive impairment among women who developed coronary heart disease.

That same month, the National Institute on Aging, part of the National Institutes of Health, awarded Shadyab a $2.1 million grant for a project that will evaluate blood-based epigenetic aging biomarkers for predicting risk of mild cognitive impairment, Alzheimer’s disease and related dementias, cognitively healthy longevity, and accelerated brain aging.

For this research, Shadyab is gathering data from the Women’s Health Initiative Memory Study which will supply blood samples for epigenomic profiling in more than 6,000 women. Because the data will be made available to the scientific community for studying the epigenomics of various age-related diseases such as cardiovascular diseases, cancer, and diabetes, as well as healthy longevity, the data could have a broad public health impact, said Shadyab.

“What’s important when we talk about human longevity science and geroscience is that we’re not just interested in lifespan — the length of someone’s life — but rather the ultimate goal is to identify strategies that can extend health span in older adults,” said Shadyab.

Health Services Research

UC San Diego RELINK Program

In 2016, facing an overwhelmed prison system, California voters passed Proposition 57 to allow incarcerated people convicted for nonviolent crimes to reduce their sentence by earning credits for sustained good behavior and participation in rehabilitation.

Although the prison population has been dropping yearly, continued overcrowding and concerns with the impact of COVID-19 outbreaks, the California Department of Corrections and Rehabilitation expanded the good behavior program to make more incarcerated people eligible to earn credits and therefore shorter sentences.

“State policy now says that a lot of people currently in prison should no longer be incarcerated. The result is that people with 10 to 30 years of prison history are returning to their communities and need help navigating re-entry to daily life,” said Victoria Ojeda, Ph.D., M.P.H., UC San Diego RELINK principal investigator and professor at the Herbert Wertheim School of Public Health.

Formerly incarcerated people who are moving back into the community are known as reentrants. After lengthy sentences they may not know how to obtain help finding work, housing or health care. They may also face persistent stigma.

While there are programs available to assist, many programs may limit how long individuals may access services after their release from prison or jail.

That’s where the UC San Diego RELINK program comes in.

RELINK serves adult reentrants living in three underserved regions of San Diego County — Central, South and East County — by using evidence-based approaches to tackle basic, vocational and health needs through service navigation, warm-handoffs to community providers, and skill-building mentorship to enhance pro-social behaviors.

“We cannot solve our clients’ concerns in a short period of time and needs may change over time, so we keep our doors open to our clients whenever they need us,” said Ojeda. “They can come back to fine-tune the support they are getting from our team.”

In July 2021, the UC San Diego RELINK Program received a grant from the California Board of State and Community Corrections through the Adult Reentry Grant Program Warm Handoff Reentry Services to provide services to reentrants 18 years and older. The program began serving clients in January 2022.

“Through this program, we hope to act as a safety net individuals with limited or no access to resources. One of our goals is to determine if providing tailored support will keep people from returning to prison,” said Ojeda, who previously ran a similar program for transition age youth (18 to 26 years old) funded by the U.S. Department of Health and Human Services Office of Minority Health.

When Ojeda arrived at UC San Diego in 2007 her research was focused on migration and health. Her research revealed that there was a critical need for helping people who had histories of incarceration and needed assistance accessing resources that might help them successfully re-enter their communities.

“The Herbert Wertheim School of Public Health aims to improve the health of the region by addressing health and social disparities. This research helps reach a community that has high level needs that are often neglected,” said Ojeda. “By helping these individuals, the entire community is benefiting.”

Mental Health and Substance Use

Characterizing the Epidemiology of Cannabidiol (CBD) Use Among U.S. Adults

Eric Leas, Ph.D., M.P.H., focused his research on tobacco regulation while studying for a doctorate in public health at UC San Diego. During that period there was a groundswell of support for the adoption of recreational cannabis laws across the U.S., sprouting a new research interest.

“First, I looked across at the cannabis marketplace and saw that many of the best practices in tobacco regulation were not being applied,” said Leas, now an assistant professor at the Herbert Wertheim School of Public Health.

“However, cannabis and tobacco are not entirely the same products. Many people think of cannabis as a medicine, but we rarely think of tobacco in this way. This distinction creates this creates a need for research into how people are using cannabis products and how best to regulate them.”

Thanks to a K01 grant he was awarded in April 2022 from the National Institute on Drug Abuse, part of the National Institutes of Health, Leas’ goal is to create the first nationally representative survey of CBD users to describe who is using CBD, why they’re using it, and whether adverse events were experienced.

CBD is a non-psychoactive chemical that can be extracted from cannabis plants including hemp, which is a cannabis plant that does not contain delta-9-THC, the main psychoactive chemical in cannabis. While recreational cannabis is legal in 19 states, Washington D.C., and Guam, CBD is currently legal in every U.S. state because of distinctions in the regulation of hemp and cannabis.

CBD products are now available in a wide variety of forms including edibles, topicals, vaping products and even dog treats. These can be sold in convenience stores and online.
CBD products have become popular in part because of claimed medical benefits. Because of this marketing, many consumers have become reluctant to see it in a negative light. Instead, they see it as harmless.

But the speed of their arrival on the market, their popularity and inconsistent regulation is cause for some concern among public health experts, said Leas.

“One of the concerns is the lack of requirements for labeling practices and testing for consistency,” said Leas.

“There are several studies that show most CBD products on the market are off label, so you could be getting much more or much less of a dose of CBD than you expect. Additionally, even when they are labeled as THC-free, some CBD products on the market may also include THC, which could lead to unintended highs.”

Leas is not calling for CBD and cannabis products to be pulled from the shelves. He wants regulation to catch up with the market so that products are safer, and consumers are educated on what, if any, health benefits are offered.

In a study published in JAMA Network Open in October 2020, Leas and co-authors concluded that consumers believed CBD could be used to treat many medical conditions that have not been scientifically proven applications of CBD. The authors suggested a public health campaign to encourage consumers to talk to their health care teams before self-medicating and restrictions on unproven marketing claims.

In October 2021, Leas authored an opinion piece in the American Journal of Public Health discussing the need to address policy loopholes that allow for the production and sale of delta-8-THC, a psychoactive substance that is also being sold with few marketing restriction. Like CBD products, delta-8-THC products are frequently mislabeled and can contain toxic chemicals that are not listed on labels.

“The ultimate goal of this research is to make a safer marketplace for cannabis products and hopefully better inform consumers more about appropriate applications of the products,” said Leas.

—Yadira Galindo