Pathways that slow down the aging of the heart

Cardiovascular disease is the leading cause of death worldwide, in part due to age-related structural dysfunction of the heart
.
On December 22, a group of bioengineers from the lab of Professor Adam Engler at the University of California, San Diego, published a paper in the journal Nature Aging, helping us deepen our understanding of cardiac aging and shed light on possible ways
to slow cardiac aging.

Dr.
Natalie Kirkland, a postdoctoral scholar in Engler's lab and first author of the paper, demonstrated with fruit flies that Lamin C, a protein responsible for maintaining the structural integrity of the heart's nucleus, declines
as fruit flies age.
The study found that the decline in lamine protein is responsible for age-induced structural remodeling in fruit fly hearts, and it may be a potential target for
slowing or even helping reverse cardiac aging in humans.

"Our study shows that age-dependent nuclear remodeling plays a key role in cardiac function," Kirkland said, "and nuclear morphology may be a marker of cell and tissue health that could be a target
for potential treatments.
" ”

Drosophila is a relatively quick and simple model to determine the cardiac preservation pathways
of interest to human studies.
Kirkland and the paper's co-author, fourth-year bioengineering undergraduate student Scott Skalak, used a microdissection technique
on the hearts of fruit flies.
The heart is then preserved and examined
with immunofluorescence and confocal microscopy.

"That's why
I first observed the nuclei of old fruit flies shrink and become rounder in their nuclei," Kirkland said.

The team then quantified this change
by splitting and measuring nuclear stiffness through atomic force microscopy.
They found that during the natural aging process, the nucleus of cardiomyocytes hardens; After genetic analysis, the researchers found that lamins expression decreased
as the flies aged.

Thanks to collaborators at the National Institute on Aging, the team was able to verify that these results also apply to mice and primates
.
This suggests that the role of lamins may also apply to human cardiac aging, which could have great therapeutic value, as targeting lamin-stimulating pathways may help avoid this mechanical change
associated with cardiac aging.

"We found the role of cardiac transcription factors in regulating cardiac contractility in adults and showed that maintaining expression of Lamin C and cardiac transcription factors can prevent age-dependent heart decline
," the researchers wrote in the study.
Our findings are conserved in older non-human primates and mice, suggesting that age-dependent nuclear remodeling is the primary mechanism
leading to cardiac dysfunction.
”

Future studies will explore why lamin is lost with age and how maintaining the expression of certain heart genes improves heart function and longevity
.

For Skalak, the experience helped him firm his decision
to apply for a PhD in bioengineering after graduating in 2023.
He learned about the importance of planning and communication to the research process, as well as various molecular biology skills
.

"In the first weeks and months of my involvement in the lab and this project, I helped Dr.
Kirkland while refining the new skills
I learned," Skalak said.
These skills include feeding and care of fruit flies, immunofluorescence, microdissection of fruit flies, and confocal microscopy
.
Over time, I acquired new skills, especially fruit fly anatomy, which allowed me to perform new experiments
independently.
This gave me the opportunity to do the experiments
needed to revise my paper in early 2022.
”