Jan Vijg

Last updated
Jan Vijg
Born
Rotterdam, Netherlands
NationalityAmerican
Scientific career
FieldsGenetics
Institutions Albert Einstein College of Medicine

Jan Vijg is the Lola and Saul Kramer Chairperson in Molecular Genetics at the Department of Genetics at the Albert Einstein College of Medicine, New York City, United States. [1] Prior to this appointment, he was a professor at the Buck Institute for Research on Aging (Novato, California).

Contents

His research interests include studying genomic instability in aging. In 1989, he created the first transgenic mouse models for the study of in vivo mutagenesis. He discusses his genomic/epigenomic drift hypothesis as a cause of aging in his book Aging of the Genome: The Dual Role of DNA in Life and Death'. [2]

In his second book, The American Technological Challenge: Stagnation and Decline in the 21st Century, he argues that technological innovation has decelerated ever since 1970. [3]

Vijg is co-editor-in-chief of the journal Aging published by Impact Journals (Albany, New York).

Genome instability in aging and disease

Genome instability, i.e., the tendency of the genome to acquire mutations and epimutations, underlies human genetic disease, causally contributes to cancer and has also been implicated in aging and age-related, degenerative conditions other than cancer. Little is known about the mechanisms that give rise to spontaneous changes in the genome or epigenome and how this may lead, in somatic cells, to increased cancer risk and loss of organ and tissue function with age. We study genome and epigenome instability as a function of age in various model organisms, including mouse and fruit fly, and its consequences in terms of alterations in tissue-specific patterns of gene regulation. We developed transgenic reporter systems in mouse and fruit fly, which allow us to determine tissue-specific frequencies of various forms of genome instability, e.g., point mutations, deletions, translocations. By crossing the mutational reporter animals with mutants harboring specific defects in various genome maintenance pathways, the relevance of these pathways for the accumulation of specific forms of genome instability is assessed, in relation to the pathophysiology of aging. Similarly, by using knockdown approaches we assess the effect of specific genes implicated in longevity and healthy aging, e.g., SOD, FOXO, SIR2, on genome integrity. More recently, we have begun to assess global gene mutation and epimutation loads in normal and disease tissues of both animal models and humans using massively parallel sequencing approaches. [1]

Books written

  1. Aging of the Genome: The Dual Role of DNA in Life and Death [4]
  2. The American Technological Challenge: Stagnation and Decline in the 21st Century [5]

Selected publications

Related Research Articles

Senescence or biological aging is the gradual deterioration of functional characteristics in living organisms. Whole organism senescence involves an increase in death rates or a decrease in fecundity with increasing age, at least in the later part of an organism's life cycle. However, the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can extend lifespans by 50% in rats, the existence of species having negligible senescence, and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.

<span class="mw-page-title-main">Nucleotide excision repair</span> DNA repair mechanism

Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals, radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR). While the BER pathway can recognize specific non-bulky lesions in DNA, it can correct only damaged bases that are removed by specific glycosylases. Similarly, the MMR pathway only targets mismatched Watson-Crick base pairs.

A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair.

Enquiry into the evolution of ageing, or aging, aims to explain why a detrimental process such as ageing would evolve, and why there is so much variability in the lifespans of organisms. The classical theories of evolution suggest that environmental factors, such as predation, accidents, disease, and/or starvation, ensure that most organisms living in natural settings will not live until old age, and so there will be very little pressure to conserve genetic changes that increase longevity. Natural selection will instead strongly favor genes which ensure early maturation and rapid reproduction, and the selection for genetic traits which promote molecular and cellular self-maintenance will decline with age for most organisms.

<span class="mw-page-title-main">Oncogenomics</span> Sub-field of genomics

Oncogenomics is a sub-field of genomics that characterizes cancer-associated genes. It focuses on genomic, epigenomic and transcript alterations in cancer.

<span class="mw-page-title-main">ERCC2</span> Mammalian protein found in humans

TFIIH subunit XPD is a protein that in humans is encoded by the ERCC2 gene. It is a component of the general transcription and DNA repair factor IIH (TFIIH) core complex involved in transcription-coupled nucleotide excision repair.

Caretaker genes encode products that stabilize the genome. Fundamentally, mutations in caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of genomic instability: mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising from improper rearrangement of chromosomes.

<span class="mw-page-title-main">ERCC1</span> Protein-coding gene in the species Homo sapiens

DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

<span class="mw-page-title-main">ERCC5</span> Protein-coding gene in the species Homo sapiens

DNA repair protein complementing XP-G cells is a protein that in humans is encoded by the ERCC5 gene.

<span class="mw-page-title-main">Cellular senescence</span> Phenomenon characterized by the cessation of cell division

Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence", or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things.

The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly or directly.

Somatic evolution is the accumulation of mutations and epimutations in somatic cells during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer.

The stem cell theory of aging postulates that the aging process is the result of the inability of various types of stem cells to continue to replenish the tissues of an organism with functional differentiated cells capable of maintaining that tissue's original function. Damage and error accumulation in genetic material is always a problem for systems regardless of the age. The number of stem cells in young people is very much higher than older people and thus creates a better and more efficient replacement mechanism in the young contrary to the old. In other words, aging is not a matter of the increase in damage, but a matter of failure to replace it due to a decreased number of stem cells. Stem cells decrease in number and tend to lose the ability to differentiate into progenies or lymphoid lineages and myeloid lineages.

Cancer genome sequencing is the whole genome sequencing of a single, homogeneous or heterogeneous group of cancer cells. It is a biochemical laboratory method for the characterization and identification of the DNA or RNA sequences of cancer cell(s).

Genome instability refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy.

Personalized onco-genomics (POG) is the field of oncology and genomics that is focused on using whole genome analysis to make personalized clinical treatment decisions. The program was devised at British Columbia's BC Cancer Agency and is currently being led by Marco Marra and Janessa Laskin. Genome instability has been identified as one of the underlying hallmarks of cancer. The genetic diversity of cancer cells promotes multiple other cancer hallmark functions that help them survive in their microenvironment and eventually metastasise. The pronounced genomic heterogeneity of tumours has led researchers to develop an approach that assesses each individual's cancer to identify targeted therapies that can halt cancer growth. Identification of these "drivers" and corresponding medications used to possibly halt these pathways are important in cancer treatment.

Human somatic variations are somatic mutations both at early stages of development and in adult cells. These variations can lead either to pathogenic phenotypes or not, even if their function in healthy conditions is not completely clear yet.

A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte. Unlike germline mutations, which can be passed on to the descendants of an organism, somatic mutations are not usually transmitted to descendants. This distinction is blurred in plants, which lack a dedicated germline, and in those animals that can reproduce asexually through mechanisms such as budding, as in members of the cnidarian genus Hydra.

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. The hallmarks of aging are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first listed in a landmark paper in 2013 to conceptualize the essence of biological aging and its underlying mechanisms.

Laura J. Niedernhofer is an American professor of biochemistry, molecular biology, and biophysics, with expertise in the fields of DNA damage, repair, progeroid syndromes and cellular senescence

References

  1. 1 2 "Jan Vijg, Ph.D." Albert Einstein College of Medicine. Archived from the original on 7 April 2014. Retrieved 16 February 2017.
  2. ↑ (http://www.sethbro.com), Content by Gelf Magazine or its credited contributors. Site design by Chris Vivion (http://www.chrisvivion.com) and Seth Bro. "Gelf Magazine An Anti-Aging Scientist Shines a Light on His Foe" . Retrieved 16 February 2017.{{cite web}}: |first= has generic name (help)
  3. ↑ Aeppel, Tim (16 June 2014). "Did We Hit Our Innovation Peak in 1970?". Wall Street Journal. Retrieved 16 February 2017.
  4. ↑ Vijg, Jan (29 March 2007). Aging of the Genome: The Dual Role of DNA in Life and Death. Oxford University Press. ISBN   978-0198569237.
  5. ↑ Vijg, Jan (15 October 2011). The American Technological Challenge: Stagnation and Decline in the 21st Century. Algora Publishing. ISBN   978-0875868851.
  6. ↑ Vijg, J (17 January 2000). "Somatic mutations and aging: a re-evaluation". Mutation Research. 447 (1): 117–35. Bibcode:2000MRFMM.447..117V. doi:10.1016/s0027-5107(99)00202-x. PMID   10686308.
  7. ↑ Hasty, P; Campisi, J; Hoeijmakers, J; van Steeg, H; Vijg, J (28 February 2003). "Aging and genome maintenance: lessons from the mouse?". Science. 299 (5611): 1355–9. doi:10.1126/science.1079161. PMID   12610296. S2CID   840477.
  8. ↑ Niedernhofer, LJ; Garinis, GA; Raams, A; Lalai, AS; Robinson, AR; Appeldoorn, E; Odijk, H; Oostendorp, R; Ahmad, A; van Leeuwen, W; Theil, AF; Vermeulen, W; van der Horst, GT; Meinecke, P; Kleijer, WJ; Vijg, J; Jaspers, NG; Hoeijmakers, JH (21 December 2006). "A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis". Nature. 444 (7122): 1038–43. Bibcode:2006Natur.444.1038N. doi:10.1038/nature05456. PMID   17183314. S2CID   4358515.
  9. ↑ Bahar, R; Hartmann, CH; Rodriguez, KA; Denny, AD; Busuttil, RA; Dollé, ME; Calder, RB; Chisholm, GB; Pollock, BH; Klein, CA; Vijg, J (22 June 2006). "Increased cell-to-cell variation in gene expression in ageing mouse heart" (PDF). Nature. 441 (7096): 1011–4. Bibcode:2006Natur.441.1011B. doi:10.1038/nature04844. hdl: 10029/5612 . PMID   16791200. S2CID   4415893.
  10. ↑ White, Ryan R.; Milholland, Brandon; de Bruin, Alain; Curran, Samuel; Laberge, Remi-Martin; van Steeg, Harry; Campisi, Judith; Maslov, Alexander Y.; Vijg, Jan (10 April 2015). "Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing". Nature Communications. 6: 6790. Bibcode:2015NatCo...6.6790W. doi:10.1038/ncomms7790. PMC   4394211 . PMID   25858675.
  11. ↑ Longo, Valter D.; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M.; Caruso, Calogero; Curiel, Tyler J.; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K.; Johnson, Thomas E.; Kennedy, Brian K.; Kenyon, Cynthia; Klein, Samuel; Kopchick, John J.; Lepperdinger, Guenter; Madeo, Frank; Mirisola, Mario G.; Mitchell, James R.; Passarino, Giuseppe; Rudolph, Karl L.; Sedivy, John M.; Shadel, Gerald S.; Sinclair, David A.; Spindler, Stephen R.; Suh, Yousin; Vijg, Jan; Vinciguerra, Manlio; Fontana, Luigi (August 2015). "Interventions to Slow Aging in Humans: Are We Ready?". Aging Cell. 14 (4): 497–510. doi:10.1111/acel.12338. PMC   4531065 . PMID   25902704.
  12. ↑ Milholland, Brandon; Auton, Adam; Suh, Yousin; Vijg, Jan (21 September 2015). "Age-related somatic mutations in the cancer genome". Oncotarget. 6 (28): 24627–24635. doi:10.18632/oncotarget.5685. PMC   4694783 . PMID   26384365.
  13. ↑ White, Ryan R.; Milholland, Brandon; MacRae, Sheila L.; Lin, Mingyan; Zheng, Deyou; Vijg, Jan (5 November 2015). "Comprehensive transcriptional landscape of aging mouse liver". BMC Genomics. 16 (1): 899. doi: 10.1186/s12864-015-2061-8 . PMC   4636074 . PMID   26541291.
  14. ↑ MacRae, Sheila L.; Croken, Matthew McKnight; Calder, R.B.; Aliper, Alexander; Milholland, Brandon; White, Ryan R.; Zhavoronkov, Alexander; Gladyshev, Vadim N.; Seluanov, Andrei; Gorbunova, Vera; Zhang, Zhengdong D.; Vijg, Jan (30 December 2015). "DNA repair in species with extreme lifespan differences". Aging. 7 (12): 1171–1182. doi:10.18632/aging.100866. PMC   4712340 . PMID   26729707.
  15. ↑ Vermeij, W. P.; Dollé, M. E. T.; Reiling, E.; Jaarsma, D.; Payan-Gomez, C.; Bombardieri, C. R.; Wu, H.; Roks, A. J. M.; Botter, S. M.; van der Eerden, B. C.; Youssef, S. A.; Kuiper, R. V.; Nagarajah, B.; van Oostrom, C. T.; Brandt, R. M. C.; Barnhoorn, S.; Imholz, S.; Pennings, J. L. A.; de Bruin, A.; Gyenis, Á.; Pothof, J.; Vijg, J.; van Steeg, H.; Hoeijmakers, J. H. J. (24 August 2016). "Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice". Nature. 537 (7620): 427–431. Bibcode:2016Natur.537..427V. doi:10.1038/nature19329. PMC   5161687 . PMID   27556946.
  16. ↑ Dong, Xiao; Milholland, Brandon; Vijg, Jan (5 October 2016). "Evidence for a limit to human lifespan". Nature. 538 (7624): 257–259. Bibcode:2016Natur.538..257D. doi:10.1038/nature19793. PMID   27706136. S2CID   3623127.
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