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USC Leonard Davis Communications

Feb 25
Headshot of Hussein Yassine with name and faculty title

Dr. Hussein Yassine: Uncovering links between nutrition, genes, and risk for Alzheimer’s disease

By Alzheimer's and Dementia, Lifespan Health, Podcast, Research

Dr. Hussein Yassine is a professor of medicine at the Keck School of Medicine at USC and is uncovering links between nutrition, genes, and risk for Alzheimer’s disease. He spoke to us about his research on APOE4, omega-3s and inflammation in the brain.

On APOE4 and Alzheimer’s risk

So APOE is a gene on chromosome 19. It exists in the population in three different forms. The two form, not very common, the three form, the most common and the four form, which makes about 20% of the population. The four form, if you get one copy from your parents, your chances of getting Alzheimer’s disease increased two to four times. If you inherit two copies, meaning you get one copy from mom and one copy from dad,  your chances of getting Alzheimer’s, or the odds ratio, goes to 12 times, meaning an APOE4 E4 homozygote, uh, 50% of those homozygotes by the age of 80 will have Alzheimer’s disease.

On the work of his lab

My lab is working to understand whether omega-3s can slow down cognitive decline in people at high risk of Alzheimer’s disease, based on APOE4. We are working on three different fronts. One, we have basic science models where we study the brains of APOE4 targeted replacement mice. We use brain imaging to study labeled DHA brain uptake in the human brain, and we do clinical trials where we give people omega-3 supplementation and look at outcomes.

On omega-3 supplements versus dietary interventions

At this point in time, we do not have high quality evidence to suggest that supplements make a difference. But we know from landmark observational cohorts, for example, the Framingham in the US, the Triple C in France, the Rotterdam in the Netherlands, and many others that people who consume at least one serving of fatty fish per week have lower risk of developing Alzheimer’s disease. In contrast trials that have involved omega-3 supplements have not panned out. And as we discussed, omega-3 supplements might be too late to be given to patients with neurodegeneration because they may not reverse neuronal death. Giving omega-3s to the general population may prove to be very difficult because the majority of people do not develop Alzheimer’s. So we need more research before we can recommend supplements. In addition, we don’t know exactly what kind of supplements we should be providing, the exact dose, the composition that duration. More research is needed to figure out those questions.

On what can people do to reduce Alzheimer’s disease risk

I think timing is key. I think if you know that you are at increased risk based on family history or APOE4 genotype  nutritional and lifestyle interventions during middle age will provide you likely the most benefit. Our research and others suggest that between the ages of 45 and 65, those at risk individuals should be on certain lifestyle modifications, whether it is at least one serving of fatty fish per week, or some good exercise regimen. We’re not talking about marathon running, maybe three times a week, 15 minutes per day is good enough. Lifestyle modifications, no smoking, reduced consumption of simple sugars to avoid complications of diabetes and obesity, increased intake of green leafy vegetables, which are enriched in polyphenols and antioxidants, good sleep, listening to music, certain forms of meditation, or in some individuals praying. And, uh, all of these factors, we know that have positive effect on mitigating or decreasing the chances of getting Alzheimer’s.

One additional factor that I did not discuss is hypertension or blood pressure control.  Blood pressure is known as a silent killer, because people have blood pressure, but they don’t know that they do so. Blood pressure control, diabetes control, cholesterol control in middle age together with these lifestyle changes can really pay dividends decades later. Once people start having symptoms and we’re talking now 60 to 80, they often come to us and they’re talking to us about omega-3 intake, about all these changes. And unfortunately at this time, the interventions are not very effective.

On the most important points  Dr. Yassine hopes people understand from  his research?

The biggest takeaway is that there is a life-course risk of Alzheimer’s disease risk in APOE4 carriers that starts shortly after birth. But mainly it takes decades before symptoms start. We know from imaging studies, between the ages of 20 all the way to 60, that the APOE4 brain is compensating to maintain cognition. Once this compensation fails, APOE4 carrier brains starts deteriorating, and you see signs of neurodegeneration and Alzheimer’s dementia. Our research emphasizes the importance of a healthy lifestyle, which includes sufficient omega-3 consumption, defined as at least one serving of fatty fish per week, lifestyle factors such as exercise, sleeping, music, meditation, family connections, combating depression, and social isolation, and social isolation is a problem now with COVID. And in addition to that, not smoking and reducing the amount of simple sugars consumed to reduce diabetes and cardiometabolic risk. Those interventions, we all know that they are critical, but our research suggests that there’s a critical time to do these interventions during middle age, to prevent the progression to Alzheimer’s at the age of 65 to 75. Once patients develop this disease, those interventions become less effective. So this is the greatest takeaway from the research we are doing.

On his message to young people

So my message to young people is that if you have a family history of Alzheimer’s disease, or that you know that you are an E4 carrier, plan in advance. Learn about the risks of Alzheimer’s disease, learn about the risks of carrying the APOE4 genotype and get informed, because we have cutting-edge research to help you out in preventing the risks of this disease early on.

On the importance of Alzheimer’s research

Up to 25% of individuals carry APOE4. So in a room of a hundred people, 25 people will have one copy of APOE4, that’s enormous. And they make the bulk, up to 50%, of patients with Alzheimer’s. We have so many APOE4 carriers in the community, and I think more research in this area is very important to the future of mitigating or changing the risk of Alzheimer’s disease. We should start early and we should try the best we can to prevent this disease because we know once it happens, it’s very difficult to treat.

On how to reach Dr. Yassine

If anybody listening to the podcast has family members with Alzheimer’s disease, they are concerned about being an APOE4 carrier and would require more advice or perhaps participate in any of our trials. Please feel free to email me. My email is hyassine@usc.edu, and you can look me up at the USC directory website and I’m happy to help.

Dec 17
Headshot of John Tower with name and faculty title

Professor John Tower: the roles of sex differences and mitochondria on aging

By Lifespan Health, Mitochondria, Podcast, Research

John Tower is a professor of biology and gerontology. He spoke to us about his research on the roles of sex differences and mitochondria in aging.

Highlights from our conversation:

As you may know, in humans, women live longer than men. And the reason for that is not entirely understood and also malfunction of the mitochondria, which is also called the powerhouse of the cell is, directly implicated in aging and multiple aging-related diseases, including Parkinson’s disease and Alzheimer’s disease and cancer. And so we’d like to understand at a very basic level, why does the mitochondria malfunction during aging and does this, or does this not have, uh, is this related to, or a result of sexual differentiation of the male and female?

While there’s no consensus in the aging field on pretty much anything. But, I would say at this point, antagonistic pleiotropy is the most favored model for how the genetics of aging works across species. And the idea is that genes can be beneficial in one context, but detrimental in another context. Specifically they’re likely to be beneficial early in life, promoting things like differentiation and growth and sexual reproduction and in the long term, the same genes are detrimental and have a cost during aging.

I’ve made a complete about face, from thinking that sexual differentiation was not important, to thinking that well, maybe sexual differentiation is actually causative to a large part in the aging process. In other words, in differentiating the male and the female, you set up the situation for sex specific trade-offs between reproduction and aging, and some aspects of these trade-offs are common between the male and the female. And some of them are unique to either the male or the female in that there are pathways that promote a reproduction, but then have a cost for the long-term maintenance of the animal. That’s the kind of antagonistic pleiotropy my lab is focusing on right now which is the idea that a gene can be beneficial to one sex, but detrimental to the other, or a gene could be detrimental to each sex in different ways

Across species, we see a decrease in mitochondrial gene expression and mitochondrial gene function during aging and the relevance to sex is that the mitochondria is transmitted to offspring only through the mother. And so this means natural selection can only optimize mitochondrial gene function for the female. This means that the male inherits a mitochondria that is less optimal for his physiology than, than it might be. And so what we see is that mitochondria isolated from female mammal tissues function better than mitochondria isolated from males consistent with this hypothesis. And so this may be one reason why females tend to live longer than males

I think what I would expect is we’re going to see sex-specific interventions in aging and aging-related diseases,  even diseases common to the male and the female, like Parkinson’s and Alzheimer’s,  that having an intervention that’s tailored, to the male or the female will be more efficacious.

Nov 23
Headshot of Kerry Burnight with name and title

Alumna Kerry Burnight: Leveraging technology to help older adults

By Careers in Aging, Lifespan Health, Podcast, Technology

Dr. Kerry Burnight is the chief gerontologist at GrandPad, the creators of an internet-connected tablet designed specifically for seniors. She spoke to us about how the device aims to combat loneliness and abuse and about the sense of purpose that powers her gerontology career.

Selected Quotes

On being a gerontologist

“To this day, if anybody asks me what I do I say I’m a gerontologist // a person who studies aging. And our goal is to try to make aging a better experience for all of us. And then people are right on board. So I think there’s like a million different ways to express your gerontology ness. And I honestly feel so like the world is the oyster of undergrad master’s and PhD gerontologist and the only thing that will hold you back is not going for it.”

On using technology to address loneliness

“And so, all things being constant being lonely or socially isolated would put you at greater risk for elder abuse and exploitation, but also at significantly greater risk for cognitive impairment for stroke for heart disease and even mortality. So you’re 25% more likely to pass away than those who are not lonely and something. //And so I was thinking, gosh, you know, maybe technology could help us.”

On providing a vulnerable senior with a GrandPad

“He was able to connect with all of us but without any of the scammers are perpetrators and so he was a guy who listened to jazz music and he loved to listen to it on his GrandPad and we did all these video calls and the reason it was so helpful is because it was so different.”

On considering seniors in technology research and development

“Standard technology creates technology targeted and built for those in their 20s and 30s// It was never designed intelligently and to honor you to honor your autonomy. //Many organizations are all about “training seniors” and it’s so silly. If you even take one step back and you think, don’t train them. It’d be like saying let’s train people to wear size two pants. No, you need to make size six pants and size eight pants and size 20 pants not shove people into the tiny pants.”

“Einstein says that the greatest sophistication is simplicity and it’s true, like the hardest thing in the world that you can do is to create something simple and it’s not because seniors are less than. It’s because we have listened. The best thing of my job is that I employ a group of seniors ages 86 to 106 who are called our grand advisors and every step of the way. It is just by listening of what matters and what doesn’t matter to people.”

On the flexibility of a gerontology degree

I say you can literally do anything you’re interested in because aging is living// My aspect now is human connection and technology. But, if you’re interested in food, you’re interested in transportation, if you’re interested in entertainment…basically, in my opinion, any facet of being a human in this time of demographic revolution needs a gerontologist to really be thinking at it in a systematic way from what it means from an aging perspective.

On the importance of stepping up to help older adults

“All you have to do is spend time with older adults and then you realize you don’t have the luxury of being shy because it’s not about you, it’s about what you can do to serve.

And actually it was a senior who told me that one time I was speaking, there was a crowd of 1000 and I was getting nervous. And so this older person said to me, ‘you need to get out of your way’. And I got really struck me that I was the one like I’m scared to talk in front of people. I don’t want to, blah, blah, blah. Get out of your way because if you’re going to help aging and our own aging, then you better get to work.”