March 10, 2011

A Model for Aging in a Dish.

One of the major difficulty in studying human aging is the duration, the human aging process takes decades to develop. The slow progression as well as the complexity of the aging process makes it very hard to study progression of cardiovascular and other related age diseases. 

Researchers at the salk institute lead by Juan-Carlos Izpisua Belmonte has reprogrammed skin cells from a child suffering from Hutchinson-Gifford progeria into induced pluripotent (iPS) stem cells and differentiated them into smooth muscle cells in a lab dish that displayed all the charachetrisic of aging cell. 

Progeria is a rare genetic disorder where symptoms resembling aspects of aging are manifested at an early age. Progeria is caused by mutation in gene encoding protein lamin A, which forms a two dimensional matrix next to the inner nuclear membrane. Mutation results in the production of truncated version of Lamin called progeria with abnormal function. 

Further in the nature paper, the salk research noted that in the embryonic-like state the lamin A was silenced, but when those cells were differentiated into smooth muscle the signs of premature aging appeared.
   
Guang-Hui Liu, Basam Z. Barkho, Sergio Ruiz, Dinh Diep, Jing Qu, Sheng-Lian Yang, Athanasia D. Panopoulos, Keiichiro Suzuki, Leo Kurian, Christopher Walsh, James Thompson, Stephanie Boue, Ho Lim Fung, Ignacio Sancho-Martinez, Kun Zhang, John Yates III, Juan Carlos Izpisua Belmonte. Recapitulation of premature ageing with iPSCs from Hutchinson–Gilford progeria syndrome. Nature, 2011; DOI: 10.1038/nature09879


March 10, 2011 by Suji George · 0

March 8, 2011

Calorie restriction reduces oxidative stress by Boosting Primary Antioxidant Defense

It has been almost years , Bob Cavanaugh is practicing severe calorie restriction. Bob Cavanaugh, managing director of the Calorie Restriction Society, is among the first to practice calorie restriction. Although the effect of “calorie restriction “ on humans is yet unknown, some are undertaking this bid to live longer . For years there has been evidence that diet low in calories extends life span. Yet we do not completely understand molecular mechanism involved in Life span extension by calorie restriction. One theory is that state of hunger act as mild stressor that makes an organism resistant to ill effect of aging. 

So how do calorie restriction evoke an anti stress response? In a recent publication in cell metabolism, a group of Berkeley Lab researchers have shown that Calorie restriction reduces oxidative stress by activating superoxide dismutase an antioxidant enzyme. Free radicals are highly reactive chemical entities that are produced as byproduct of normal metabolic process. The antioxidant defense system consisting of enzymes including superoxide dismutase protects cells from free radical assault. A major cause of aging and numerous diseases is thought to be cumulative oxidative stress, resulting from the production of reactive free radicals during respiration.

In this study the researchers created a knockout mice missing a gene that produces a mitochondrial enzyme Sirt3. Under similar calorie restriction regime, the Knockout mouse failed to respond to beneficial effects of CR such as reduction in oxidative stress. Further it was shown that sirt3 reduces cellular free radicals by activating a crucial antioxidant enzyme superoxide dismutase. It removes acetyl moiety from two critical lysine residues on SOD and promotes its free radical scavenging activity.  

The study takes us one step closer to understanding the molecular mechanism involved in life span extension by CR. 

Qiu X, Brown K, Hirschey MD, Verdin E, Chen D (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab: 12(6):662-667.

March 8, 2011 by Suji George · 0