Tactic to Delay Age-Related Disorders

ScienceDaily (Nov. 2, 2011) — Researchers at Mayo Clinic have shown that eliminating cells that accumulate with age could prevent or delay the onset of age-related disorders and disabilities. The study, performed in mouse models, provides the first evidence that these "deadbeat" cells could contribute to aging and suggests a way to help people stay healthier as they age.

The findings appear in the journal Nature, along with an independent commentary on the discovery.

"By attacking these cells and what they produce, one day we may be able to break the link between aging mechanisms and predisposition to diseases like heart disease, stroke, cancers and dementia," says co-author James Kirkland, M.D., Ph.D., head of Mayo's Robert and Arlene Kogod Center on Aging and the Noaber Foundation Professor of Aging Research. "There is potential for a fundamental change in the way we provide treatment for chronic diseases in older people."

Five decades ago, scientists discovered that cells undergo a limited number of divisions before they stop dividing. At that point the cells reach a state of limbo -- called cellular senescence -- where they neither die nor continue to multiply. They produce factors that damage adjacent cells and cause tissue inflammation. This alternative cell fate is believed to be a mechanism to prevent runaway cell growth and the spread of cancer. The immune system sweeps out these dysfunctional cells on a regular basis, but over time becomes less effective at "keeping house."

As a result, senescent cells accumulate with age. Whether and how these cells cause age-related diseases and dysfunction has been a major open question in the field of aging. One reason the question has been so difficult to answer is that the numbers of senescent cells are quite limited and comprise at most only 10 to 15 percent of cells in an elderly individual.

"Our discovery demonstrates that in our body cells are accumulating that cause these age-related disorders and discomforts," says senior author Jan van Deursen, Ph.D., a Mayo Clinic molecular biologist and the Vita Valley Professor of Cellular Senescence. "Therapeutic interventions to get rid of senescent cells or block their effects may represent an avenue to make us feel more vital, healthier, and allow us to stay independent for a much longer time."

"Through their novel methodology, the research team found that deletion of senescent cells in genetically engineered mice led to improvement in at least some aspects of the physiology of these animals. So, with the caveat that the study involved a mouse model displaying accelerated aging, this paper provides important insights on aging at the cellular level," says Felipe Sierra, Ph.D., Director of the Division of Aging Biology, National Institute on Aging, National Institutes of Health.

How They Did It

Dr. van Deursen and colleagues genetically engineered mice so their senescent cells harbored a molecule called caspase 8 that was only turned on in the presence of a drug that has no effect on normal cells. When the transgenic mice were exposed to this drug, caspase 8 was activated in the senescent cells, drilling holes in the cell membrane to specifically kill the senescent cells.

The researchers found that lifelong elimination of senescent cells delayed the onset of age-related disorders such as cataracts and muscle loss and weakness. Perhaps even more importantly, they showed that removing these cells later in life could slow the progression of already established age-related disorders.

The findings support a role of senescent cells in the aging process and indicate that chemicals secreted by these cells contribute to age-related tissue dysfunction and disease.

Other co-authors of the article are: Darren Baker, Ph.D., Tamar Tchkonia, Ph.D., Nathan LeBrasseur, Ph.D. and Bennett Childs, all of Mayo Clinic; and Tobias Wijshake and Bart van de Sluis, Ph.D., both of Groningen University, The Netherlands. The Ellison Medical Foundation, the Noaber Foundation, the Robert and Arlene Kogod Center on Aging, and the National Institutes of Health funded the study.

Story Source:

The above story is reprinted from materials provided by Mayo Clinic.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1. Darren J. Baker, Tobias Wijshake, Tamar Tchkonia, Nathan K. LeBrasseur, Bennett G. Childs, Bart van de Sluis, James L. Kirkland, Jan M. van Deursen. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 2011; DOI: 10.1038/nature10600

Mitochondria: Body’s Power Stations Can Affect Aging

ScienceDaily (May 10, 2011) — Mitochondria are the body's energy producers, the power stations inside our cells. Researchers at the University of Gothenburg, Sweden, have now identified a group of mitochondrial proteins, the absence of which allows other protein groups to stabilise the genome. This could delay the onset of age-related diseases and increase lifespan.

Some theories of human aging suggest that the power generators of the cell, the mitochondria, play a part in the process. In addition to supplying us with energy in a usable form, mitochondria also produce harmful by-products -- reactive oxyradicals that attack and damage various cell components. Eventually these injuries become too much for the cell to cope with, and it loses its capacity to maintain important functions, so the organism starts to age. That's the theory anyway. Oddly enough, several studies have shown that certain mitochondrial dysfunctions can actually delay aging, at least in fungi, worms and flies. The underlying mechanisms have yet to be determined.

In a study from the Department of Cell and Molecular Biology at the University of Gothenburg, published in the journal Molecular Cell, a research team has now identified a group of mitochondrial proteins that are involved in this type of aging regulation. The researchers found that a group of proteins called MTC proteins, which are normally needed for mitochondrial protein synthesis, also have other functions that influence genome stability and the cell's capacity to remove damaged and harmful proteins.

"When a certain MTC protein is lacking in the cell, e.g. because of a mutation in the corresponding gene, the other MTC proteins appear to adopt a new function. They then gain increased significance for the stabilisation of the genome and for combating protein damage, which leads to increased lifespan," says Thomas Nyström of the Department of Cell and Molecular Biology.

He adds, "These studies also show that this MTC-dependent regulation of the rate of aging uses the same signalling pathways that are activated in calorie restriction -- something that extends the lifespan of many different organisms, including yeasts, mice and primates. Some of the MTC proteins identified in this study can also be found in the human cell, raising the obvious question of whether they play a similar role in the regulation of our own aging processes. It is possible that modulating the activity of the MTC proteins could enable us to improve the capacity of the cell to delay the onset of age-related diseases. These include diseases related to instability of the genome, such as cancer, as well as those related to harmful proteins, such as Alzheimer's disease and Parkinson's disease. At the moment this is only speculation, and the precise mechanism underlying the role of the MTC proteins in the aging process is a fascinating question that remains to be answered."

Story Source:

The above story is reprinted from materials provided by University of Gothenburg, via AlphaGalileo.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1. Antonio Caballero, Ana Ugidos, Beidong Liu, David Öling, Kristian Kvint, Xinxin Hao, Cora Mignat, Laurence Nachin, Mikael Molin, Thomas Nyström. Absence of Mitochondrial Translation Control Proteins Extends Life Span by Activating Sirtuin-Dependent Silencing. Molecular Cell, 2011; 42 (3): 390 DOI: 10.1016/j.molcel.2011.03.021

The treatment:

In past articles, I have outlined many anti aging supplements. Among the most effective and the most scientific data have narrowed the list to the anthocianins in fruit, and the polephenol compounds otherwise known as: Reservatrol, Grape seed extract, berry extracts and whole blueberries, cherries, blackberries.

Blessings,

Robert