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Senolytic Drugs: From Discovery to Translation

Kirkland JL1, Tchkonia T2.

J Intern Med. 2020 Jul 19. doi: 10.1111/joim.13141. [Epub ahead of print]

Senolytics are a class of drugs that selectively clear senescent cells (SC). The first senolytic drugs Dasatinib, Quercetin, Fisetin, and Navitoclax were discovered using a hypothesis-driven approach. SC accumulate with aging and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality, and health expenditures. The most deleterious SC are resistant to apoptosis and have up-regulation of anti-apoptotic pathways which defend SC against their own inflammatory senescence-associated secretory phenotype (SASP), allowing them to survive, despite killing neighboring cells. Senolytics transiently disable these SCAPs, causing apoptosis of those SC with a tissue-destructive SASP. Because SC take weeks to re-accumulate, senolytics can be administered intermittently – a «hit-and-run» approach. In pre-clinical models, senolytics delay, prevent, or alleviate frailty, cancers, and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, hematological, metabolic, and skin disorders as well as complications of organ transplantation, radiation, and cancer treatment. As anticipated for agents targeting the fundamental aging mechanisms that are «root cause» contributors to multiple disorders, potential uses of senolytics are protean, potentially alleviating over 40 conditions in preclinical studies, opening a new route for treating age-related dysfunction and diseases. Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation, and alleviate frailty in humans. Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer’s disease, COVID-19, osteoarthritis, osteoporosis, eye diseases, and bone marrow transplant and childhood cancer survivors are underway or beginning. Until such studies are done, it is too early for senolytics to be used outside of clinical trials.

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Edo. Bolívar

Presidente: Dr. Guillermo Herrera (Ginecólogo)

Secretario: Dra. Falva Acosta (Gineco-Obstetra)

Tesorero: Dra. Ximena Madrid (Cardiología)

Vocal: Dra. Wilmania Bouchard Dra. Mercedes Santomauro (Endocrinología)

Edo. Mérida

Presidente: Dra. María Eugenia Noguera  (Ginecobstetra)

Secretario: Dra. Nazira Monsalve (Ginecobstetra)

Tesorero: Dra. Juleida Askul (Endocrinóloga)

Vocal: Dra. Lelis Quintero (Ginecobstetra)

Vocal: Dra. Maira Useche (Cardióloga)

Edo. Táchira

Presidente: Dr. Álvaro Padilla  (Ginecología y Obstetricia)

Secretario: Dra. Raiza Bontemps (Ginecología y Obstetricia)

Tesorero: Dr. Luis Ernesto Jaimes (Endocrinología)

Vocal: Dra. Maria Hercilia Esteva (Reumatología)

Vocal: Dr. Renny Cárdenas  (Traumatología)

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Edo. Falcón

Presidente: Dra. Ma. Auxiliadora Curiel  (Gineco-Obstetra)

Secretario: Dr. Arnaldo Acosta (Endocrinólogo).

Tesorero: Dra. Lourdes Aldama (Gineco-Obstetra)

Edo. Sucre

Presidente: Dra. Haydee Rodríguez de Sánchez  (Ginecología)

Secretario: Dra. Esmely Salazar  (Ginecología y Obstetricia)

Tesorero: Dr. Luis Diaz (Cardiología)

Miembros Fundadores

Miembros Fundadores ( Sociedad Venezolana de Osteoporosis)

  1. Ada Perdomo
  2. Adolfo Melendez
  3. Alberto Zuloaga
  4. Alfonso Jacir
  5. Alfonso Vergara
  6. Alfredo Guariguata
  7. Alfredo Posada
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  13. Antonio Tarrazzi Salazar
  14. Bernardo Birnbaum
  15. Carlos Sandrea
  16. Carlos Soto Rivera
  17. Carmen Afonzo De Hernández
  18. Daniela Jakubowicz
  19. Douglas Ponce
  20. Douglas Urbina Oteiza
  21. Eddie Kaswan
  22. Eddy Alberto Salazar
  23. Eduardo Coll García
  24. Eladio R. Diaz Camero
  25. Elías Salazar Aboud
  26. Elie Nehme
  27. Elio Antonio Romero S.
  28. Eva Essenfeld De Sekler
  29. Eva Mariela Salazar
  30. Ezequiel Bellorin Font
  31. Ezequiel Hidalgo
  32. Florencio Quintero Rojo
  33. Francisco Carelli F
  34. Francisco Pinto
  35. Francisco Tapanes
  36. Frank Gorrochotegui
  37. Froino Gartner K.
  38. Gary Sterba
  39. Guillermo Bajares
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  53. José R García Cervén
  54. José Quijada Palacios
  55. José Rafael Roura
  56. José Weissinger
  57. Juan Antonio Yabur
  58. Juan Bautista Zambrano
  59. Juan F. Duque Pernía
  60. Julieta V. De Bello
  61. Jusés Mazzei Berti
  62. Leopoldo Baptista
  63. Leslie Sánchez
  64. Lilia Pérez De Rivero
  65. Luis A. Hernández
  66. Luis Alberto Blanco Acevedo
  67. Luis Alejandro Rodriguez
  68. Luis Alfredo Rodriguez
  69. Luis E. Rodriguez Mora
  70. Luis J. González Leon
  71. Mariá Eugenia De D´Empaire
  72. Marcos Troccoli
  73. María Carmen Cordido
  74. Maria Cristina Angelino De Blanco
  75. Maria Luisa Cumaná De López
  76. María Maiello De Betancourt
  77. María Zoraida Pacheco
  78. Mario Ogni
  79. Miguel Padilla
  80. Miriam Alvarado
  81. Moisés R.Attias
  82. Nancy Negrín De Moreno
  83. Nujem Szomsteim
  84. Oscar J. Solís
  85. Oswaldo Pbregón
  86. Pablo Amair M
  87. Pedro Armas
  88. Pedro Jose Vicentelli
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  90. Pedro Teppa
  91. Rafael Rodríguez Cedeño
  92. Ramón Castro
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  94. Ramón Franco
  95. Raúl J. Fernández Barboza
  96. Raúl Veitia
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  98. Rodrigo Infante
  99. Ronal Paredes
  100. Rosa Hernández Gandolfi
  101. Rubén Jaén
  102. Ruben Quintero Monasterios
  103. Rufino Rengifo
  104. Salvador Rivas
  105. Samuel Abbo
  106. Sergio Tovar
  107. Vicente Franco De Lugo
  108. Virgilio Paz Martínez
  109. Xabier Arozena
  110. Yolanda Díaz De Perdomo
  111. Yolanda Salazar
  112. Zoraida Paz

 

Miembros Fundadores ( SOVEMO)

  1. Alfredo Guariguata
  2. Anabella San Vicente
  3. Andrés Mendoza
  4. Antonio De Santolo
  5. Antonio Tarrazzi
  6. Bernardo Birbaum
  7. Carlos Soto Rivera
  8. Desiderio Rincón Pacheco
  9. Douglas Ponce
  10. Douglas Urbina
  11. Edgar Nieto
  12. Eduardo Coll García
  13. Eladio Díaz Camero
  14. Elias Salazar
  15. Elie Nehme
  16. Eva Mariela Salazar
  17. Farid Atías
  18. Florencio Quintero Rojo
  19. Francisco Tapanes
  20. Frank Gorrochotegui
  21. Froino Gartner
  22. Gary Sterba
  23. Gregorio Riera
  24. Guillermo Bajares
  25. Gunter Lentz
  26. Humberto Acosta
  27. Ibrahim Pazos
  28. Isidoro Bronstein
  29. Jonny Engler
  30. Jorge Cedeño
  31. José Delgado
  32. José R. García
  33. Juan Antonio Yabur
  34. Julieta De Bello
  35. Leopoldo Baptista
  36. Leslie Sánchez
  37. Luis González León
  38. María C. Maiello De Betancourt
  39. María Carmen Cordido
  40. María Cristina Angelino De Blanco
  41. María Eugenia De D’empaire
  42. Mariela Bajares De Lilue
  43. Miriam Alvarado
  44. Moisés Atias
  45. Nujem Szomstein
  46. Pablo Amair
  47. Pedro Armas
  48. Pedro Vicentelli
  49. Ramón González Cerruti
  50. Raúl Fernández
  51. Raúl Veitía
  52. Rosa Hernández
  53. Rubén Quintero
  54. Rufino Rengifo
  55. Sergio Tovar
  56. Valmore Quintero