An update on the LysoSENS research project from the SENS Foundation, which aims to discover and adapt bacterial enzymes to break down the damaging buildup of unwanted metabolic byproducts in the aging body: "SENS Foundation-funded research shows that expression of a modified microbial enzyme protects human cells against 7-ketocholesterol toxicity, advancing research toward remediation of the foam cell and rejuvenation of the atherosclerotic artery. ... Atherosclerotic cardiovascular disease is the principal cause of ischaemic heart disease, cerebrovascular disease, and peripheral vascular disease, making it the root of the leading cause of morbidity and mortality worldwide. Atherosclerosis begins with the entrapment and oxidation of low-density lipoprotein (LDL) cholesterol in the arterial endothelium. As a protective response, the endothelium recruits blood monocytes into the arterial wall, which differentiate and mature into active macrophages and engulf toxic oxidized cholesterol products (oxysterols) such as 7-ketocholesterol (7-KC). Although initially protective, this response ultimately leads to atherosclerotic plaque: oxidized cholesterol products accumulate in the macrophage lysosome, and impair the processing and trafficking of native cholesterol and other materials, leading macrophages to become dysfunctional and immobilized ... more and more of these disabled "foam cells" progressively accumulate in the arterial wall, generating the fatty streaks that form the basis of the atherosclerotic lesion. Rejuvenation biotechnology can be brought to bear against this disease of aging through the identification, modification, and therapeutic delivery of novel lysosomal enzymes derived from microbes to the arterial macrophage - enzymes which are capable of degrading oxidized cholesterol products. SENS Foundation-funded researchers have been making steady progress in the identification and characterization of candidate enzymes for several years now, and a new report represents a substantial advance in the research: the rescue of cellular oxysterol toxicity by an introduced microbial lysosomal enzyme."

Link: http://sens.org/node/2737

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

You might recall research published last near on NRG-1 levels in naked mole-rats. Here is an update: "The typical naked mole rat lives 25 to 30 years, during which it shows little decline in activity, bone health, reproductive capacity and cognitive ability. ... Naked mole rats have the highest level of a growth factor called NRG-1 in the cerebellum. Its levels are sustained throughout their life, from development through adulthood. ... NRG-1 levels were monitored in naked mole rats at different ages ranging from a day to 26 years. The other six rodent species have maximum life spans of three to 19 years. The cerebellum coordinates movements and maintains bodily equilibrium. The research team hypothesized that long-lived species would maintain higher levels of NRG-1 in this region of the brain, with simultaneous healthy activity levels. Among each of the species, the longest-lived members exhibited the highest lifelong levels of NRG-1. The naked mole rat had the most robust and enduring supply. ... In both mice and in humans, NRG-1 levels go down with age ... The strong correlation between this protective brain factor and maximum life span highlights a new focus for aging research, further supporting earlier findings that it is not the amount of oxidative damage an organism encounters that determines species life span but rather that the protective mechanisms may be more important."

Link: http://www.mysanantonio.com/life/health/article/The-secret-of-long-life-may-be-in-a-naked-mole-rat-3543091.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The choroid plexus is, amongst other things, a filter for cerebrospinal fluid - you might think of this role as analogous to that of the kidney as a filter for blood, though the two organs are very different in structure at every level, and the choroid plexus also produces the fluid it filters. Like all of the systems in the body and brain, the choroid plexus progressively fails in its function with age, and researchers have reason to believe that this failure contributes to conditions such as Alzheimer's disease:

An organ in the brain called the choroid plexus apparently plays a critical role in preventing the accumulation of a protein associated with Alzheimer's disease. The researchers found that the choroid plexus acts as a sort of 'fishnet' that captures the protein, called beta-amyloid, and prevents it from building up in the cerebrospinal fluid, which surrounds and bathes the brain and spinal cord. Moreover, tissue in the organ is able to soak up large amounts of the protein and may contain enzymes capable of digesting beta-amyloid.

Levels of beta-amyloid in the brain are more dynamic than their slow buildup over the years implies. You might think of the condition - and indeed the increase in amyloid levels in aging in general - as a slowly progressing imbalance of amyloid creation and clearance mechanisms rather than a slow and irrevocable deposition of amyloid. That in turn implies that a working therapy could quickly reverse all but the latest stages of the disease, when neurons are dying in large numbers.

Do rising brain levels of a plaque-forming substance mean patients are making more of it or that they can no longer clear it from their brains as effectively? ... Clearance is impaired in Alzheimer's disease. We compared a group of 12 patients with early Alzheimer's disease to 12 age-matched and cognitively normal subjects. Both groups produced amyloid-beta (a-beta) at the same average rate, but there's an average drop of about 30 percent in the clearance rates of the group with Alzheimer's. ... Scientists calculate this week [that] it would take 10 years for this decrease in clearance to cause a build-up of a-beta equal to those seen in the brains of Alzheimer's patients. The results have important implications for both diagnosis and treatment.

Here is a more recent paper that reviews what is known of the role of the choroid plexus:

Pathological Alteration in the Choroid Plexus of Alzheimer's Disease: Implication for New Therapy Approaches

In the recent years, much attention has been directed to the roles of the choroid plexus in the central nervous system (CNS) under both normal and pathological conditions. This specialized ventricular structure has recently emerged as a key player in a variety of processes that monitor and maintain the biochemical and cellular homeostasis of the CNS.

The main role of the choroid plexus is to produce cerebrospinal fluid (CSF) and to maintain the extracellular environment of the brain by monitoring the chemical exchange between the CSF and the brain tissue. This involves the surveying of the chemical and immunological status of the extracellular fluid and the removal of toxic substances as well as important roles in the regenerative processes following traumatic events. In addition to CSF, the plexus produces various peptides which can have nourishing and neuroprotective properties.

...

Morphological alterations of choroid plexus in Alzheimer's disease (AD) have been extensively investigated. These changes include epithelial atrophy, thickening of the basement membrane, and stroma fibrosis. As a result, synthesis, secretory, and transportation functions are significantly altered resulting in decreased cerebrospinal fluid (CSF) turnover. Recent studies discuss the potential impacts of these changes, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to the amyloid peptide.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The choroid plexus is, amongst other things, a filter for cerebrospinal fluid - you might think of this role as analogous to that of the kidney as a filter for blood, though the two organs are very different in structure at every level, and the choroid plexus also produces the fluid it filters. Like all of the systems in the body and brain, the choroid plexus progressively fails in its function with age, and researchers have reason to believe that this failure contributes to conditions such as Alzheimer's disease:

An organ in the brain called the choroid plexus apparently plays a critical role in preventing the accumulation of a protein associated with Alzheimer's disease. The researchers found that the choroid plexus acts as a sort of 'fishnet' that captures the protein, called beta-amyloid, and prevents it from building up in the cerebrospinal fluid, which surrounds and bathes the brain and spinal cord. Moreover, tissue in the organ is able to soak up large amounts of the protein and may contain enzymes capable of digesting beta-amyloid.

Levels of beta-amyloid in the brain are more dynamic than their slow buildup over the years implies. You might think of the condition - and indeed the increase in amyloid levels in aging in general - as a slowly progressing imbalance of amyloid creation and clearance mechanisms rather than a slow and irrevocable deposition of amyloid. That in turn implies that a working therapy could quickly reverse all but the latest stages of the disease, when neurons are dying in large numbers.

Do rising brain levels of a plaque-forming substance mean patients are making more of it or that they can no longer clear it from their brains as effectively? ... Clearance is impaired in Alzheimer's disease. We compared a group of 12 patients with early Alzheimer's disease to 12 age-matched and cognitively normal subjects. Both groups produced amyloid-beta (a-beta) at the same average rate, but there's an average drop of about 30 percent in the clearance rates of the group with Alzheimer's. ... Scientists calculate this week [that] it would take 10 years for this decrease in clearance to cause a build-up of a-beta equal to those seen in the brains of Alzheimer's patients. The results have important implications for both diagnosis and treatment.

Here is a more recent paper that reviews what is known of the role of the choroid plexus:

Pathological Alteration in the Choroid Plexus of Alzheimer's Disease: Implication for New Therapy Approaches

In the recent years, much attention has been directed to the roles of the choroid plexus in the central nervous system (CNS) under both normal and pathological conditions. This specialized ventricular structure has recently emerged as a key player in a variety of processes that monitor and maintain the biochemical and cellular homeostasis of the CNS.

The main role of the choroid plexus is to produce cerebrospinal fluid (CSF) and to maintain the extracellular environment of the brain by monitoring the chemical exchange between the CSF and the brain tissue. This involves the surveying of the chemical and immunological status of the extracellular fluid and the removal of toxic substances as well as important roles in the regenerative processes following traumatic events. In addition to CSF, the plexus produces various peptides which can have nourishing and neuroprotective properties.

...

Morphological alterations of choroid plexus in Alzheimer's disease (AD) have been extensively investigated. These changes include epithelial atrophy, thickening of the basement membrane, and stroma fibrosis. As a result, synthesis, secretory, and transportation functions are significantly altered resulting in decreased cerebrospinal fluid (CSF) turnover. Recent studies discuss the potential impacts of these changes, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to the amyloid peptide.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm