Theorizing a Role for Prelamin A in Aging

Researchers here review the evidence for prelamin A to have a role in aging. This derives from research into the LMNA mutation that results in Hutchinson-Gilford progeria syndrome, as normal prelamin A has some commonalities with the mutated lamin A, called progerin, that produces pathology in that condition. As is always the case, the mechanisms look plausible, but the question remains open as to whether this does in fact produce a meaningful contribution to aging. The only way to find out is to downregulate prelamin A efficiently without affecting other mechanisms of aging, and see what happens.

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, 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. Here, we describe mechanisms underlying changes in prelamin A with aging and lay out the case that this unprocessed protein impacts normative aging. This is impo...

Source: Fight Aging! - October 27, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs