Aging | Lamin A to Z in Normal Aging

Aging-US

“It has long been debated to what extent the mechanisms of aging and progeria overlap.”

BUFFALO, NY- November 9, 2022 – A new research perspective was published in Aging (listed as “Aging (Albany NY)” by MEDLINE/PubMed and “Aging-US” by Web of Science) Volume 14, Issue 20, entitled, “Lamin A to Z in normal aging.”

Almost since the discovery that mutations in the LMNA gene, encoding the nuclear structure components lamin A and C, lead to Hutchinson-Gilford progeria syndrome (HGPS), people have speculated that lamins may have a role in normal aging. 

The most common HPGS mutation creates a splice variant of lamin A, progerin, which promotes accelerated aging pathology. While some evidence exists that progerin accumulates with normal aging, an increasing body of work indicates that prelamin A, a precursor of lamin A prior to C-terminal proteolytic processing, accumulates with age and may be a driver of normal aging. Prelamin A shares properties with progerin and is also linked to a rare progeroid disease, restrictive dermopathy. 

“Patients with the laminopathy, restrictive dermopathy (RD), have mutations in either ZMPSTE24 or LMNA, the latter associated with altered processing and the accumulation of prelamin A [4, 29]. RD has some phenotypes of accelerated aging; however, the condition is often very early onset and severe, making comparison with normal aging more challenging.”

In this new research perspective, researchers Stanley R. Primmer, Chen-Yu Liao, Oona M.P. Kummert, and Brian K. Kennedy from the Buck Institute for Research on Aging, National University of Singapore and National University Health System describe mechanisms underlying changes in prelamin A with aging and lay out the case that this unprocessed protein impacts normative aging. 

“This is important since intervention strategies can be developed to modify this pathway as a means to extend healthspan and lifespan.”

DOI: https://doi.org/10.18632/aging.204342 

Corresponding Author: Brian K. Kennedy – Corresponding Email: [email protected] 

Keywords: lamin A, prelamin A, zmpste24, mTOR, aging

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Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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