Telomerase Reverse Transcriptase Synergizes with Calorie Restriction to Increase Health Span and Extend Mouse Longevity

Abstract

Caloric restriction (CR), a reduction of food intake while avoiding malnutrition, can delay the onset of cancer and age-related diseases in several species, including mice. In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background. Given the CR cancer-protective effects in rodents, we set to address here whether CR impacts on telomere length and synergizes with mTERT to extend mouse longevity. CR significantly decreased tumor incidence in TERT transgenic (TgTERT) mice and extended their lifespan compared to wild-type (WT) controls under the same diet, indicating a synergy between TgTERT and CR in increasing mouse longevity. In addition, longitudinal telomere length measurements in peripheral blood leukocytes from individual mice showed that CR resulted in maintenance and/or elongation telomeres in a percentage of WT mice, a situation that mimics telomere dynamics in TgTERT cohorts. These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing “health span” and extending mouse longevity.

Seventy years after the siege of Leningrad

“…Moderate caloric restriction is beneficial for reduction of telomere shortening [11]; lifestyle can also be essential for telomere length, but little is known about the effects of severe starvation on telomere length.…”

Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

“…82 There are several studies suggesting an increased expression in miRNA network that modulates the inflammatory profile of neural and glial cells, also affecting behavioral aspects and, therefore, influences the epigenetics, 79,83 or the cells' telomerase activity by accelerating or slowing down the process of cerebral aging. 84 In this sense, accelerated brain aging by environmental components, behavioral or genetic, makes the brain structure vulnerable to two distinct disease processes, which are associated in some situations: i) oxidative stress modulating the chronic accumulation of protein clusters (a-synuclein, β amyloid, Tau, etc) or intracellular apoptotic/degenerative events by the increased immune response, and ii) the ischemic event, acute in most situations, caused by trauma or thromboembolic events. 48 AD, Parkinson's disease, stroke, and sclerosis are the most prevalent diseases related to the cerebral aging process.…”

Epigenetic linkage of aging, cancer and nutrition

“…It is known that cancer cells metabolize glucose at an elevated rate compared with normal cells, and it is this phenomenon that makes glucose restriction a novel therapeutic approach in the impairment of cancer growth and progression. Moreover, CR improves insulin sensitivity and causes its subsequent decrease in response to a reduction in glucose levels (Vera et al, 2013). A reduction of caloric consumption in humans has also been linked to reduced risks of diabetes and cardiovascular disease (Fontana and Klein, 2007;Cruzen and Colman, 2009).…”

“…CR has also been shown to both decrease the incidence and delay the onset of various age-related diseases, such as artherosclerosis and neurodegenerative diseases in humans and primates (Roth et al, 2001;Holloszy and Fontana, 2007;Colman et al, 2009). The exact mechanisms by which CR affects aging, age-related diseases and cancer are debated, although there is a strong suggestion that CR promotes protective mechanisms that allow evasion from DNA damage (Bordone and Guarente, 2005;Vera et al, 2013).…”