As Chris Patil of Ouroboros points out, the latest issue of the Journal of Pathology focuses on the pathology of aging - accumulated molecular damage leads to failure of organs and processes, named diseases of aging, and then suffering and death. Against that backdrop, I am pleased to more often see echos of the intent and thinking behind SENS, the Strategies for Engineered Negligible Senescence, out in the scientific community these days. Strong ideas don't exist in a sealed realm; rather they are diffuse at the edges, spreading to cause change. The active efforts of SENS supporters help that process along - and so we can hope to see ever more scientists declaring that something can be done about aging:
The mechanisms of cellular ageing at a genetic, protein and organelle level are becoming clearer, as are some of the more complex associations between environment and ageing. System ageing is also becoming better understood, and the potential biological advantages of ageing are being explored. Many of the advances in these fields are opening up the prospect of targeted therapeutic intervention for ageing and age related disease.
As Chris Patil notes, "The devotion of an entire issue to this subject is just the latest example of the increasing mainstream attention being paid to the biology of aging." There's a lot of good stuff in there, but this caught my eye:
As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy and other degradative systems, long-lived postmitotic cells, such as cardiac myocytes, neurons and retinal pigment epithelial cells, progressively accumulate biological garbage (waste materials). The latter include lipofuscin (a non-degradable intralysosomal polymeric substance), defective mitochondria and other organelles, and aberrant proteins, often forming aggregates (aggresomes). An interaction between senescent lipofuscin-loaded lysosomes and mitochondria seems to play a pivotal role in the progress of cellular ageing. Lipofuscin deposition hampers autophagic mitochondrial turnover, promoting the accumulation of senescent mitochondria, which are deficient in ATP production but produce increased amounts of reactive oxygen species. Increased oxidative stress, in turn, further enhances damage to both mitochondria and lysosomes, thus diminishing adaptability, triggering mitochondrial and lysosomal pro-apoptotic pathways, and culminating in cell death.
In other words, you need well-functioning lysosomes (the little recycling plants inside your cells that digest failing components and damaging chemicals) to keep your mitochondria (the power plants inside your cells) in good shape. Mitochondria need to be replaced when they are damaged, or else they can start to damage the cell that hosts them - and that damage is a cause of aging. But simply living across the decades generates an ever-increasing load of biochemical junk that lysosomes can't deal with; eventually they become bloated and inefficient.
Long-time readers of this blog will find this an interesting link between past posts on the mitochondrial free radical theory of aging, methods to tackle lipofuscin buildup, and the lysoSENS project - the latter being a search for bacterial enzymes that can degrade and remove this buildup of "biological garbage" in lysosomes and elsewhere in your cells.
The paper above is a good reminder that many classes of age-related cellular damage feed off one another; damage accelerates damage in all failing machinery. This is all the more reason to accelerate the search for ways and means to fix these problems before they kill us!