Aging: past, present and future

Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion Abstract Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age accelerati...

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption Abstract Recent research has proposed that GIT2 (G protein-coupled receptor kinase interacting protein 2) acts as an integrator of the aging process through regulation of ‘neurometabolic’ integrity. One of the commonly accepted hallmarks of the aging process is thymic involution. At a relatively young age, 12 months old, GIT2 -/-  mice present a prematurely distorted thymic structure and dysfunction compared to age-matched 12 month-old wild-type control (C57BL/6) mice. Disruption of thymic structure in GIT2 -/-  (GIT2KO) mice was associated with a significant reduction in the expression of the cortical thymic marker,  Troma-I  (cytokeratin 8). Double positive (CD4 + CD8 + ) and single positive CD4 +  T cells were also markedly reduced in 12 month-old GIT2KO mice compared to age-matched control wild-type mice. Coincident with this premature thymic dis...

Circadian clock-coordinated hepatic lipid metabolism: only transcriptional regulation Abstract By regulating the metabolism of fatty acids, carbohydrates, and xenobiotic, the mammalian circadian clock plays a fundamental role on the liver physiology. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. However, recent evidences suggest that some signaling pathways synchronized by the circadian clock can also influence metabolism at a post-transcriptional level. In this context, we have recently shown that the circadian clock synchronizes the rhythmic activation of the IRE1α pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock, provokes deregulation of endoplasmic reticulum-localized enzymes, and leads to impaired lipid metabolism. We will describe here the additional pathways synchronized by the clock and discussed the influence of the cir...

Quantifying pharmacologic suppression of cellular senescence: prevention of cellular hypertrophy versus preservation of proliferative potential Zoya N. Demidenko 1 , 2   ,   Mikhail V. Blagosklonny 1 , 2 1  Oncotarget, Buffalo, NY 14263, USA 2  Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263 Received: May 25, 2009          Accepted: December 30, 2009          Published: December 31, 2009 https://doi.org/10.18632/aging.100115 How to Cite Abstract Development of agents that suppress aging (aging suppressants) requires quantification of cellular senescence. Cellular senescence in vitro is characterized by a large cell morphology and permanent loss of proliferative potential. When HT-1080 cells were arrested by p21, they continued to grow exponentially in size and became hypertrophic with a 15-fold increase in the protein content per cell. These changes were mirrored by accumulation of GFP (...

Aging: past, present and future  Mikhail V. Blagosklonny In his Foundation series, published in the 1950’s, Isaac Asimov imagined Civilization capable of colonizing the entire Universe. This feat is unlikely to occur. Strikingly, Asimov referred to a 70-old man as an old individual who is unlikely to live much longer. Thus, in literature’s most daring fantasy, the pace of aging could not be slowed. Yet, given the present pace of discovery in the aging field, this feat might become a reality within our life time, with science surpassing science fiction. PAST Once August Weismann had divided life into a perishable soma and immortal germ line, the soma began to be viewed as disposable. As Weismann wrote in 1889, “the perishable and vulnerable nature of the soma was the reason why nature made no effort to endow this part of the individual with a life of unlimited length” (see [1]). Weismann speculated that somatic mortality might give the individual benefits early in life, such as “a ...