CRONA - Calorie Restriction with Optimal Nutrition and Aging
Limiting calories slows aging at the genetic/cell signaling level – a comprehensive exploration.
On behalf of the CR Society International and The CR Way Longevity Center, we are pleased to announce the launch of CRONA, a new research study on the effects of calorie restriction on human aging.See the CR Way Research forum for updates about participating in the CR cohort and other study details.
Project Investigators
Dr Elizabeth Blackburn's identification of telomerase as an enzyme crucial to the successful replication of chromosomes in cell division is hailed as one of the most important discoveries in the field of molecular genetics.
The capped ends of chromosomes, called telomeres, maintain DNA integrity, which is particularly important during cell division, when mutations might be likely. Telomerase enables telomeres to replicate fully. For more on telomeres, telomerase and cell division see
The Telomere -- Function and Synthesis.
"Genetic material can get very messed up if you do not have a special cap on the chromosomes," said Blackburn. She used a shoelace analogy to illustrate "If you don’t have those little tips on both ends of your shoelace, the shoelace frays," she said. Even worse, without telomeres, broken chromosome ends combine with any other end they find and that is not good for the health of the organism. It's as though someone ties your shoe laces together and makes you fall over."*
*Department of Innovation, Industry, Science and Research, Copyright © Commonwealth of Australia
Dr. Blackburn's work has already influenced The CR Way through her collaboration on "Accelerated telomere shortening in response to life stress, " a study reported worldwide and showing for the first time that stress may accelerate aging. For more about how DR. Blackburn and colleagues discovered telomeres and how they work read "The Ends Have Arrived" by by VA Zakian.
Anne Brunet (Dept of Genetics, Stanford)
Anne Brunet is well known for her her work on "longevity genes," FOXOs and Sirtuins.
She was principal investigator of a 2004 study showing that interaction between SIRT1 and FOXO3a shifted cellular actions away from apoptosis, increasing cell resistance.
Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase.
Science. 2004 Feb 19
Brunet A et al
The Sir2 deacetylase modulates organismal lifespan in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homologue SIRT1 appears to control the cellular response to stress by regulating FOXO transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.
PMID: 14976264
As
principal investigator of the research linking chronic stress shortened telomere
length, Dr. Epel had a major influence on The CR Way, making us aware that
telomere length is a likely aging marker and that chronic stress hastens
telomere shortening. In fact, the 2004 study in which she collaborated
with Dr. Elizabeth Blackburn, prompted us to integrate meditation into the CR
Way lifestyle:
Accelerated
telomere shortening in response to life stress.
Epel
ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM.
Proc
Natl Acad Sci U S A. 2004 Dec 14;101(50):17323-4.
Numerous
studies demonstrate links between chronic stress and indices of poor health,
including risk factors for cardiovascular disease and poorer immune function.
Nevertheless, the exact mechanisms of how stress gets "under the
skin" remain elusive. We investigated the hypothesis that stress impacts
health by modulating the rate of cellular aging. Here we provide evidence that
psychological stress--both perceived stress and chronicity of stress--is
significantly associated with higher oxidative stress, lower telomerase
activity, and shorter telomere length, which are known determinants of cell
senescence and longevity, in peripheral blood mononuclear cells from healthy
premenopausal women. Women with the highest levels of perceived stress have
telomeres shorter on average by the equivalent of at least one decade of
additional aging compared to low stress women. These findings have
implications for understanding how, at the cellular level, stress may promote
earlier onset of age-related diseases.
PMID:
15574496
Pankaj Kapahi (Buck Institute for Age Research) the lab of Dr. Kapahi was the first to identify the role of mTOR (mammalian