Mammalian Models of Extended Healthy Lifespan

Overview

Journal Philos Trans R Soc Lond B Biol Sci

Specialty Biology

Date 2010 Dec 1

PMID 21115536

Citations 35

Authors

Colin Selman

Dominic J Withers

Affiliations

Soon will be listed here.

Abstract

Over the last two centuries, there has been a significant increase in average lifespan expectancy in the developed world. One unambiguous clinical implication of getting older is the risk of experiencing age-related diseases including various cancers, dementia, type-2 diabetes, cataracts and osteoporosis. Historically, the ageing process and its consequences were thought to be intractable. However, over the last two decades or so, a wealth of empirical data has been generated which demonstrates that longevity in model organisms can be extended through the manipulation of individual genes. In particular, many pathological conditions associated with the ageing process in model organisms, and importantly conserved from nematodes to humans, are attenuated in long-lived genetic mutants. For example, several long-lived genetic mouse models show attenuation in age-related cognitive decline, adiposity, cancer and glucose intolerance. Therefore, these long-lived mice enjoy a longer period without suffering the various sequelae of ageing. The greatest challenge in the biology of ageing is to now identify the mechanisms underlying increased healthy lifespan in these model organisms. Given that the elderly are making up an increasingly greater proportion of society, this focused approach in model organisms should help identify tractable interventions that can ultimately be translated to humans.

Citing Articles

Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan.

Borland G, Wilkie S, Thomson J, Wang Z, Tullet J, Alic N Aging Cell. 2024; 23(5):e14141.

PMID: 38465473 PMC: 11113255. DOI: 10.1111/acel.14141.

PRMT1 orchestrates with SAMTOR to govern mTORC1 methionine sensing via Arg-methylation of NPRL2.

Jiang C, Liu J, He S, Xu W, Huang R, Pan W Cell Metab. 2023; 35(12):2183-2199.e7.

PMID: 38006878 PMC: 11192564. DOI: 10.1016/j.cmet.2023.11.001.

Metabolomics Community in Russia: History of Development, Key Participants, and Results.

Balashova E, Maslov D, Trifonova O BioTech (Basel). 2022; 9(4).

PMID: 35822823 PMC: 9258313. DOI: 10.3390/biotech9040020.

Age-Related Lysosomal Dysfunctions.

Guerrero-Navarro L, Jansen-Durr P, Cavinato M Cells. 2022; 11(12).

PMID: 35741106 PMC: 9221958. DOI: 10.3390/cells11121977.

Triggering receptor expressed on myeloid cells-2 promotes survival of cardiomyocytes after myocardial ischemic injury through PI3K/AKT pathway.

Fu C, Xu Q, Liu J, Tang S, Liu C, Cao Y Cardiovasc Diagn Ther. 2022; 12(1):24-36.

PMID: 35282669 PMC: 8898683. DOI: 10.21037/cdt-21-490.

References

Dai D, Chen T, Wanagat J, Laflamme M, Marcinek D, Emond M . Age-dependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria. Aging Cell. 2010; 9(4):536-44. PMC: 3265170. DOI: 10.1111/j.1474-9726.2010.00581.x. View

Dominici F, Arostegui Diaz G, Bartke A, Kopchick J, Turyn D . Compensatory alterations of insulin signal transduction in liver of growth hormone receptor knockout mice. J Endocrinol. 2000; 166(3):579-90. DOI: 10.1677/joe.0.1660579. View

Kurosu H, Yamamoto M, Clark J, Pastor J, Nandi A, Gurnani P . Suppression of aging in mice by the hormone Klotho. Science. 2005; 309(5742):1829-33. PMC: 2536606. DOI: 10.1126/science.1112766. View

Kenyon C . The genetics of ageing. Nature. 2010; 464(7288):504-12. DOI: 10.1038/nature08980. View

Schriner S, Linford N, Martin G, Treuting P, Ogburn C, Emond M . Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005; 308(5730):1909-11. DOI: 10.1126/science.1106653. View

Partridge L, Gems D, Withers D . Sex and death: what is the connection?. Cell. 2005; 120(4):461-72. DOI: 10.1016/j.cell.2005.01.026. View

Hagen T . Oxidative stress, redox imbalance, and the aging process. Antioxid Redox Signal. 2003; 5(5):503-6. DOI: 10.1089/152308603770310149. View

van Heemst D, Beekman M, Mooijaart S, Heijmans B, Brandt B, Zwaan B . Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005; 4(2):79-85. DOI: 10.1111/j.1474-9728.2005.00148.x. View

Christensen K, Doblhammer G, Rau R, Vaupel J . Ageing populations: the challenges ahead. Lancet. 2009; 374(9696):1196-208. PMC: 2810516. DOI: 10.1016/S0140-6736(09)61460-4. View

10.

Spilman P, Podlutskaya N, Hart M, Debnath J, Gorostiza O, Bredesen D . Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS One. 2010; 5(4):e9979. PMC: 2848616. DOI: 10.1371/journal.pone.0009979. View

11.

Kapahi P, Zid B, Harper T, Koslover D, Sapin V, Benzer S . Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004; 14(10):885-90. PMC: 2754830. DOI: 10.1016/j.cub.2004.03.059. View

12.

Khosla S . Update in male osteoporosis. J Clin Endocrinol Metab. 2010; 95(1):3-10. PMC: 2805483. DOI: 10.1210/jc.2009-1740. View

13.

Sarkar D, Fisher P . Molecular mechanisms of aging-associated inflammation. Cancer Lett. 2005; 236(1):13-23. DOI: 10.1016/j.canlet.2005.04.009. View

14.

Ikeno Y, Bronson R, Hubbard G, Lee S, Bartke A . Delayed occurrence of fatal neoplastic diseases in ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci. 2003; 58(4):291-6. DOI: 10.1093/gerona/58.4.b291. View

15.

Page M, Salmon A, Leiser S, Robb E, Brown M, Miller R . Mechanisms of stress resistance in Snell dwarf mouse fibroblasts: enhanced antioxidant and DNA base excision repair capacity, but no differences in mitochondrial metabolism. Free Radic Biol Med. 2009; 46(8):1109-18. PMC: 2683197. DOI: 10.1016/j.freeradbiomed.2009.01.014. View

16.

Salmon A, Murakami S, Bartke A, Kopchick J, Yasumura K, Miller R . Fibroblast cell lines from young adult mice of long-lived mutant strains are resistant to multiple forms of stress. Am J Physiol Endocrinol Metab. 2005; 289(1):E23-9. DOI: 10.1152/ajpendo.00575.2004. View

17.

Suh Y, Atzmon G, Cho M, Hwang D, Liu B, Leahy D . Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci U S A. 2008; 105(9):3438-42. PMC: 2265137. DOI: 10.1073/pnas.0705467105. View

18.

Murray C, Lopez A . Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 1997; 349(9061):1269-76. DOI: 10.1016/S0140-6736(96)07493-4. View

19.

Karakelides H, Irving B, Short K, OBrien P, Nair K . Age, obesity, and sex effects on insulin sensitivity and skeletal muscle mitochondrial function. Diabetes. 2009; 59(1):89-97. PMC: 2797949. DOI: 10.2337/db09-0591. View

20.

Hsieh C, Deford J, Flurkey K, Harrison D, Papaconstantinou J . Implications for the insulin signaling pathway in Snell dwarf mouse longevity: a similarity with the C. elegans longevity paradigm. Mech Ageing Dev. 2002; 123(9):1229-44. DOI: 10.1016/s0047-6374(02)00036-2. View