Suicide of aging cells prolongs life span in mice

first_imgThey are lurking in your heart, your liver, your kidneys, and maybe even your brain: run-down cells that could be making you age. A new study of mice shows that spurring these so-called senescent cells to self-destruct extends the animals’ lives  and delays some aspects of aging.“It’s a landmark paper,” says cell and molecular biologist Francis Rodier of the University of Montreal in Canada, who wasn’t connected to the study. “It’s providing biological evidence that senescence is involved in the aging process.”Cells senesce after suffering DNA damage or other types of stress. Although they remain alive, senescent cells lose the ability to divide. Researchers think that this cellular birth control evolved to thwart the formation of tumors, but it provides other benefits as well. The stagnant cells release chemicals that help wounds heal, for instance. But senescence also causes harm. If stem cells stop dividing, organs can deteriorate because they can’t replace cells that have died. Furthermore, the chemicals released by senescent cells can damage surrounding tissues and, to researchers’ surprise, promote tumor growth. Our bodies build up senescent cells as we get older, and researchers have been trying to nail down their impact on aging for more than 50 years. Cancer biologist Jan van Deursen of the Mayo Clinic College of Medicine in Rochester, Minnesota, and colleagues took a direct approach to the problem, genetically engineering a strain of fast-aging mice so that their senescent cells committed suicide in response to a drug. In 2011, the researchers revealed that pruning senescent cells from the mice slowed their physical breakdown as they got older—although it didn’t extend their lives.To find out if the approach worked in rodents other than the fast-aging mice, van Deursen and colleagues genetically modified two other mouse strains to kill their own senescent cells after receiving the same drug. When the rodents reached middle age, the researchers began injecting them with the compound twice a week. Although the procedure couldn’t eliminate senescent cells from the animals, it could kill 50% to 70% of them in some tissues, van Deursen says.After undergoing the treatment for 6 months, the mice were healthier in many ways than a set of control animals. As the scientists report online today in Nature, pruning senescent cells reduced the amount of damage to the blood-filtering structures in the kidneys. The animals’ hearts were better able to cope with stress than were the hearts of control mice. Even the behaviors of the treated mice were different. They were more daring and youthful than the control mice. Like middle-aged folks who’d rather watch TV than hit the clubs, the controls were less active and more reluctant to explore new environments.But the finding that grabbed the researchers’ attention was that destroying senescent cells boosted the average life span of the two mouse strains by more than 20%. Some of the increased longevity may have stemmed from a beneficial effect on cancer. Removal of senescent cells didn’t prevent tumors from forming in the rodents, but it did slow their growth. “It had more of an impact on life span than I would have predicted,” van Deursen says.Not all age-related problems in the mice improved, however. Their memory, muscle strength, coordination, and balance—all of which decline as we grow older—were no better than those of control rodents. Deleting senescent cells doesn’t spare the animals from aging entirely, van Deursen says. “It has an attenuating effect. You still get age-dependent [changes], and the mice still die.”“This study is a big step toward validating the approach of targeting senescent cells,” says cell biologist Christian Sell of Drexel University College of Medicine in Philadelphia, Pennsylvania, who wasn’t connected to the research.   Scientists have identified other approaches that slow aging in experimental animals, such as deleting certain genes or drastically cutting calories, notes geneticist Ned Sharpless of the University of North Carolina School of Medicine in Chapel Hill. However, says Sharpless, who wasn’t connected to the research but did help found a company that makes a diagnostic test for senescent cells, these approaches are impractical for humans. For example, some would require a person to take a drug for decades to see only a small effect, he says. But deleting senescent cells could be feasible in people, he says. For the first time, a researcher can say, “if I can figure out a way to kill senescent cells with a small molecule or an antibody, I could do a clinical trial.”In fact, clinical trials might not be that far off. The mice in the study were genetically altered to respond to the drug, but a company that van Deursen co-founded and a separate group of researchers have already discovered compounds that can kill senescent cells in unmodified mice. It might soon be possible to test whether removing these cells can forestall age-related diseases, such as atherosclerosis, that cause so much suffering as we get older, van Deursen says. “We accumulate senescent cells, and they take away healthy years.” Email Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwecenter_img Sign up for our daily newsletter Get more great content like this delivered right to you! 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