Nir Barzilai | |
---|---|
Born | Haifa, Israel | December 27, 1955
Citizenship | United States of America and Israel |
Alma mater | Technion-Israel Institute of Technology |
Known for | biology of aging, genetics of exceptional longevity |
Awards | Irving S. Wright Award of Distinction in Aging Research Award (September 2010) |
Scientific career | |
Fields | genetics and biology of aging, endocrinology/diabetes |
Institutions | Albert Einstein College of Medicine |
Nir Barzilai (born December 27, 1955) is an Israeli geneticist and longevity researcher.
Barzilai is the founding director of the Institute for Aging Research, [1] the Nathan Shock Center of Excellence in the Basic Biology of Aging and the Paul F. Glenn Center for the Biology of Human Aging Research at Albert Einstein College of Medicine (Einstein). He also directs the Longevity Genes Project, [2] a genetics study of over 600 families of centenarians and their children. The participants are all Ashkenazi Jews, a group selected for their genetic homogeneity, which makes it easier to identify significant genetic variations. Barzilai found that many of the centenarians had very high levels of HDL. [3] Barzilai also co-founded of CohBar, Inc., a biotechnology company developing mitochondria based therapeutics to treat diseases associated with aging.
Barzilai discovered several “longevity genes” in humans that were validated by others. [4] These include variants in genes involved in cholesterol metabolism (CETP [5] and APOC3 [6] ), metabolism (ADIPOQ [7] and TSHR [8] ) and growth (IGF1R [9] ). These genes appear to protect centenarians against major age-related diseases, such as cardiovascular disease, cancer, type 2 diabetes and dementia. [10]
Treatments for age-related diseases were under development based on Barzilai’s work. A collaboration with Merck conducted early-stage clinical trials but ultimately abandoned Anacetrapib. The diabetes research is led by CohBar Inc., [11] a biotech company that Barzilai helped co-found.
In addition to his “longevity gene” research, Barzilai studies key mechanisms involved in the biology of aging, including how nutrients [12] and genetics [13] influence lifespan. He has also proposed metformin as a tool to target aging [14] and has run the Metformin in Longevity Study (completed May 2018) [15] He is also investigating how mental decline and personality affect longevity. [16] Barzilai believes that metformin will extend human lifespan. He has pointed to studies suggesting that diabetics who take metformin tend to live longer than non-diabetics. In support of this, a large study previously showed that diabetic patients on metformin had a longer lifespan compared to non-diabetic individuals who were not on the drug. [17]
Barzilai was born in Haifa, Israel. During his national service in the Israel Defense Forces, he served as a medical instructor. In 1976, he served as a medical officer in Operation Entebbe. He was the Israeli army's chief medic from 1977 to 1985. He studied medicine at the Technion – Israel Institute of Technology, obtaining his MD in 1985. He interned at Rambam Medical Center in Haifa, Hadassah Medical Center in Jerusalem, and the Royal Free Hospital in London. He first came to the U.S. in 1987 as a resident at Yale University. He joined Einstein in 1993 as an instructor of medicine (endocrinology). [18] [19]
Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled biological limit of around 125 years. Several researchers in the area, along with "life extensionists", "immortalists", or "longevists", postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition (agerasia). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.
Longevity may refer to especially long-lived members of a population, whereas life expectancy is defined statistically as the average number of years remaining at a given age. For example, a population's life expectancy at birth is the same as the average age at death for all people born in the same year.
Haptoglobin is the protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds with high affinity to free hemoglobin released from erythrocytes, and thereby inhibits its deleterious oxidative activity. Compared to Hp, hemopexin binds to free heme. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system.
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of Type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, and is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics. It has also been shown to inhibit inflammation, and is not associated with weight gain. Metformin is taken orally.
Heteroplasmy is the presence of more than one type of organellar genome within a cell or individual. It is an important factor in considering the severity of mitochondrial diseases. Because most eukaryotic cells contain many hundreds of mitochondria with hundreds of copies of mitochondrial DNA, it is common for mutations to affect only some mitochondria, leaving most unaffected.
Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low-density (VLDL) or Chylomicrons and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a heteroexchange, trading a triglyceride for a cholesteryl ester or a cholesteryl ester for a triglyceride.
Apolipoprotein E (Apo-E) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular diseases. It is encoded in humans by the gene APOE.
Battenin is a protein that in humans is encoded by the CLN3 gene located on chromosome 16. Battenin is not clustered into any Pfam clan, but it is included in the TCDB suggesting that it is a transporter. In humans, it belongs to the atypical SLCs due to its structural and phylogenetic similarity to other SLC transporters.
In genomics, a genome-wide association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.
Forkhead box O3, also known as FOXO3 or FOXO3a, is a human protein encoded by the FOXO3 gene.
Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene.
Paola Sebastiani is a biostatistician and a professor at Boston University working in the field of genetic epidemiology, building prognostic models that can be used for the dissection of complex traits. Her research interests include Bayesian modeling of biomedical data, particularly genetic and genomic data.
A centenarian is a person who has attained the age of 100 years or more. Research on centenarians has become more common with clinical and general population studies now having been conducted in France, Hungary, Japan, Italy, Finland, Denmark, the United States, and China. Centenarians are the second fastest-growing demographic in much of the developed world. By 2030, it is expected that there will be around a million centenarians worldwide. In the United States, a 2010 Census Bureau report found that more than 80 percent of centenarians are women.
The medical genetics of Jews have been studied to identify and prevent some rare genetic diseases that, while still rare, are more common than average among people of Jewish descent. There are several autosomal recessive genetic disorders that are more common than average in ethnically Jewish populations, particularly Ashkenazi Jews, because of relatively recent population bottlenecks and because of consanguineous marriage. These two phenomena reduce genetic diversity and raise the chance that two parents will carry a mutation in the same gene and pass on both mutations to a child.
Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.
Humanin is a micropeptide encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2. Its structure contains a three-turn α-helix, and no symmetry.
Epigenetic therapy refers to the use of drugs or other interventions to modify gene expression patterns, potentially treating diseases by targeting epigenetic mechanisms such as DNA methylation and histone modifications.
In biogerontology, the disposable soma theory of aging states that organisms age due to an evolutionary trade-off between growth, reproduction, and DNA repair maintenance. Formulated by British biologist Thomas Kirkwood, the disposable soma theory explains that an organism only has a limited amount of resources that it can allocate to its various cellular processes. Therefore, a greater investment in growth and reproduction would result in reduced investment in DNA repair maintenance, leading to increased cellular damage, shortened telomeres, accumulation of mutations, compromised stem cells, and ultimately, senescence. Although many models, both animal and human, have appeared to support this theory, parts of it are still controversial. Specifically, while the evolutionary trade-off between growth and aging has been well established, the relationship between reproduction and aging is still without scientific consensus, and the cellular mechanisms largely undiscovered.
Katalin Susztak (Suszták) is a Hungarian American scientist and nephrologist at the Perelman School of Medicine at the University of Pennsylvania. She is a professor of medicine and genetics, and currently the codirector of the Complications Unit at the Institute for Diabetes, Obesity and Metabolism. Her laboratory made major contributions to the current understanding of kidney disease development. She is also the founder of the Transformative Research In DiabEtic NephropaThy (TRIDENT), a collaborative network of physicians and basic scientists, to find cures for diabetic kidney disease.
Itsik Pe'er is a computational biologist and a Full Professor in the Department of Computer Science at Columbia University.
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