Likars'ka Sprava / Ministerstvo Okhorony Zdorov'ia UkraÔny
Telomeres are the ends of chromosomes and are non-coding DNA "end-capped" with structures containing DNA-quadruplexes and proteins. Telomeres become shorter after each cell division, which is one of the mechanisms of gradual ageing. Telomerase is the reverse transcriptase responsible for the extension of telomere length. It is well known that activation of telomerase in the most types of organism's cells is not enough for telomere length stabilization. The reason may be in the telomere "caps", which cover telomere ends from telomerase action.
During development and aging, vascular remodeling represents a critical adaptive response to modifications in oxygen supply to tissues. Hypoxia inducible factor (HIF) has a crucial role and is modulated by oxygen levels, with an age-dependent response in neonates, adult, and aged people. ROS are generated under hypoxic conditions and the accumulation of free radicals during life reduces the ability of tissues to their removal.
Aging is associated with high incidence of ischemic diseases, which go along with a drop in tissue oxygenation. At the molecular level the hypoxia inducible factor (HIF) is the master regulator for hypoxia-induced gene expression. Recent studies demonstrated age-related changes in the HIF system, which might explain the reduced ability to cope with hypoxia in elderly. There are also some evidences that HIF is functionally connected to the aging process itself.
There is an imperative need for exploring and implementing mitochondria-rejuvenative interventions that can bridge the current gap toward the step-by step realization of strategies for engineered negligible senescence (SENS) agenda. Recently discovered in mammals, natural mechanism mitoptosis-a selective "suicide" of mutated mitochondria-can facilitate continuous purification of mitochondrial pool in an organism from the most reactive oxygen species (ROS)-producing mitochondria.
Journal of the American Society of Nephrology: JASN
Sirtuins (silent information regulator 2 [Sir2] proteins) belong to an ancient family of evolutionary conserved nicotinamide adenine dinucleotide (NAD)(+)-dependent enzymes with deacetylase and/or mono-ADP-ribosyltransferase activity. They regulate DNA repair and recombination, chromosomal stability, and gene transcription, and most importantly mediate the health-promoting effects of caloric restriction (CR), which includes the retardation of aging. At least seven Sir2 homologs, sirtuins (SIRT) 1 to 7 have been identified in mammals.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Stabilization of the hypoxia-inducible factor (HIF-1) protein extends longevity in Caenorhabditis elegans. However, stabilization of mammalian HIF-1? has been implicated in tumor growth and cancer development. Consequently, for the hypoxic response to benefit mammalian health, we must determine the components of the response that contribute to longevity, and separate them from those that cause harm in mammals. Here, we subject adult worms to low oxygen environments. We find that growth in hypoxia increases longevity in wild-type worms but not in animals lacking HIF-1 or DAF-16.
Pharmacological effects of ifenprodil (IP), 4-benzyl-alpha-(p-hydroxyphenyl)-beta-methyl-1-piperidineethanol-L-(+)-tartrate monohydrate (Funai Pharmaceutical), a potential vasodilator, were studied in the dog, rabbit, guinea-pig and mouse. 1) Intravenous administration of IP (0.1 approximately 1 mg/kg) exhibited a continuous fall in blood pressure, an increase in heart rate and an increase in cardiac contractile force in the dog. The depressor and chronotropic effects of IP appeared likewise in the pithed dog, and the depressor responses were slightly more evident in the rabbit.
The mechanism which normally affects distribution of blood flow through unventilated areas of the lung is hypoxic pulmonary vasoconstriction; this acts to divert the blood to well ventilated alveoli, resulting in a better ratio of ventilation to perfusion. Several reports have focused attention on the reduction or abolition of this reflex in the unventilated lung by most of the volatile anaesthetic agents used in clinical practice. This response was not abolished by the intravenous anaesthetic agents.
We have studied the effects of chlormethiazole infusion on the ventilatory response to progressive isocapnic hypoxia in seven healthy volunteers, during both normocapnia and induced hypercapnia. The dose of chlormethiazole was such that it produced the same degree of hypnosis as would be expected from oral administration of two capsules each containing 192 mg of base in arachis oil. Ventilation did not change significantly during chlormethiazole administration. The ventilatory response to hypoxia was unaffected by chlormethiazole during normocapnia and was enhanced during hypercapnia.
BACKGROUND: In humans the ventilatory response to isocapnic hypoxia is biphasic: an initial increase in minute ventilation (VE) from baseline, the acute hypoxic response, is followed after 3-5 min by a slow ventilatory decay, the hypoxic ventilatory decline, and a new steady state, 25-40% greater than baseline VE, is reached in about 15-20 min. The transition from 20 min of isocapnic hypoxia into normoxia results in a rapid decrease in VE, the off-response. In humans, halothane, at subanesthetic concentrations, is known to decrease the acute hypoxic response.