June 30, 2011

Interventional anti-aging

Melanie Swan covered the 40th annual meeting of the American Aging Association held June 3-6, 2011 in Raleigh NC USA. They covered emerging concepts in the mechanisms of aging.

Many usual topics in aging were covered such as dietary restriction (DR), inflammation, stress resistance, homeostasis and proteasome activity, sarcopenia, and neural degeneration.

Newer methods like microRNAs and genome sequencing were employed to investigate gene expression variance with aging and genetic signatures of longevity.

Melanie has a full 13 page report

Many of the conference talks had a translational focus, applying the biology of aging to the development of anti-aging interventions:

* Using an individual’s own stem cells to regenerate organs for transplantation and as a cell source for cellular therapies could be a powerful near-term solution to disease.

* Several proposed interventions were pharmaceutical, myostatin inhibition, losartan, JAK pathway inhibitors, and enalapril for frailty and sarcopenia, and metformin to promote Nrf2 anti-inflammation response.

* In dietary restriction, protein restriction was found to be better than general caloric restriction. Short-term fasting may be helpful in chemotherapy, surgery, and acute stress, simultaneously increasing the killing of cancer cells by chemotherapy, while improving the survival of normal cells.

* Dietary restriction mimetics, most promisingly involving TOR (TORC1 inhibition and rapamycin), may be more feasible than dietary restriction.

* Immune system interventions remain elusive, although statins may help to improve cellular-senescence promoted bacterial infection.

* Engineered enzymes may be useful in lysosomal catabolism.

Personalized therapies: organ regeneration and stem cells
One of the most exciting, and possibly near-term solutions for aging-related conditions is regenerative medicine, using an individual’s own stem cells to recreate organs for transplantation and as a cell source for cellular therapies. Regenerative medicine efforts are currently underway in 20-30 organs. There are also numerous uses for stem cell therapies, two discussed here are improving neural stem cell genesis and treating neurodegenerative disease, and ameliorating telomere dysfunction present in both aging pathologies and disease states.

Shay Soker (Wake Forest University) presented an overview of Anthony Atala lab’s wide range of preeminent regenerative medicine work. Existing progress has been made in the organ regeneration of bladders, urethras, and tracheas, and additional work is underway in the liver, kidney, pancreas, intestine, and other organs. Making regenerated organs fully functional may involve several tricky steps. For example in working with cardiomyocytes, experiments are being conducted to facilitate cell-cell communication by incorporating connexin, a protein that assembles to form gap junctions between cells and is important for the coordinated depolarization of cardiac muscle. A second example is working with urinary incontinence, where urine-holding muscles weaken. Research is looking at the injection of chondrocytes (cells found in cartilage which produce and maintain the cartilaginous matrix) into dog bladders.

Translational aging research: remedy of frailty and sarcopenia

A translational aging research session focused on ameliorating frailty and sarcopenia.

Sarcopenia is characterized mainly as an excessive reduction in skeletal muscle mass, but also includes changes in adiposity. It is an ‘undefined’ condition in that it is not yet prescribable and does not have agreed-upon measurement parameters and cut-off points for intervention. One definitional approach could be measuring loss of function in physical performance, for example gait speed has been linked with survival in humans as well as falls and Timed Up and Go (TUG) capability. Frailty, on the other hand, is a diagnosable geriatric syndrome which is defined by one or more factors: a decline in strength and activity, an increase in inflammation, involuntary weight loss, exhaustion,slow walking speed, and reduced grip strength. Proposed interventions were pharmacological including myostatin inhibition, losartan, JAK pathway inhibitors, and enalapril.

Nathan LeBrasseur (Mayo Clinic) investigated the signaling and transcriptional
regulatory pathways involved in increasing muscle mass and glycolytic capacity.
The high degree of plasticity in skeletal muscle suggests the potential success of
interventions such as resistance training, genetic alterations, and pharmaceuticals.

Myostatin inhibition was examined for its potential to improve muscle mass, physical
function, and metabolism in mice and humans

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