A Hidden Trick for Cell Cleansing Could Reverse the Aging Process

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that causes children to show signs of accelerated aging. Those affected often develop wrinkles at an early age, lose skin elasticity, have less body fat, suffer from hair loss, arteriosclerosis, and insulin resistance. Scientists have discovered that about 90% of HGPS cases are caused by a defective protein called progerin.

Activating the Cells’ Cleaning System Could be the Secret to Staying Young Longer

Progerin has a harmful “dominant-negative” effect on cells, which means that it impairs normal cell function. This abnormal protein triggers several cellular problems, such as deformation of the nuclear envelope (NE), increased DNA damage, shortened telomeres, cell cycle arrest, and reduced division capacity. Interestingly, there is growing evidence that small amounts of progerin are also present in the natural aging process and in chronic kidney disease (CKD). For this reason, therapies that promote the removal of progerin may be promising for the treatment of HGPS, CKD, and other age-related diseases.

A research team led by Professor Chuanmao Zhang of Peking University and Kunming University of Science and Technology has long been engaged in research into the biological mechanisms behind aging and progeria. In a recent study published in Science China Life Sciences, the group identified a key process in which lysosomes—tiny cell compartments responsible for breaking down waste materials—play a central role in the elimination of progerin.

Their study found that defects in lysosomes contribute to the accumulation of progerin in HGPS cells. More importantly, they were able to demonstrate that stimulating lysosomal activity can restore this “cleaning function” of cells, removing progerin and reducing signs of cellular aging. These discoveries make lysosomes an important new target for potential therapies for HGPS, CKD, and other age-related diseases.

How Progerin Accumulates in Cells

Using a combination of immunofluorescence imaging, live cell observation, and biochemical analysis, the researchers tracked how progerin behaves in the cells. They observed that progerin, which initially appears near the nuclear envelope, can enter the cell’s cytoplasm through a process called nuclear envelope budding. Once in the cytoplasm, progerin should normally be degraded via the cell’s autophagy-lysosome pathway, an important recycling system.

However, this system does not function efficiently in HGPS cells, allowing progerin to accumulate. To investigate the reason for this, the team performed RNA sequencing on primary cells from two patients with HGPS. The results showed a significant reduction in the activity of genes associated with lysosomal function. Further tests, including RT-qPCR, immunofluorescence, and biochemical assays, confirmed that the lysosomes in these cells were indeed defective.

Restoring Lysosomal Function to Combat the Aging Process

Next, the researchers tested whether repairing the lysosomal defects could improve progerin clearance and slow down cell aging. They activated lysosomal biogenesis—the process by which new lysosomes are formed—using two methods: by stimulating protein kinase C (PKC) or by inhibiting the mammalian target of rapamycin complex 1 (mTORC1).

Both approaches successfully improved lysosome function, promoted the removal of progerin, and reduced signs of cellular aging such as DNA damage, growth arrest, and loss of cell vitality. These results suggest that reviving the body’s own cleaning mechanism could help reverse some of the harmful effects of progerin accumulation.

Towards Anti-Aging Therapies Targeting Lysosomes

This research clearly demonstrates that lysosomes play a key role in removing progerin and maintaining cell health. It also points to the activation of lysosomes as a potential strategy for combating premature and natural aging. By specifically targeting the body’s recycling systems, scientists may ultimately find new ways to treat HGPS and a variety of age-related diseases.