The dynamic nature of ageing: novel findings, therapeutic avenues and medical interventions

Authors

  • Piotr Paweł Chmielewski Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wrocław

DOI:

https://doi.org/10.2478/anre-2020-0001

Keywords:

ageing, epigenetic clocks, epigenetic mechanisms, homeodynamics, human longevity, hyperfunction, senescence

Abstract

Ageing is one of the most complex and difficult problems for humans to face and for science to solve. Although human senescence was viewed as a passive and uncontrollable process of deteriora­tion over time with little or no genetic regulation, the concept that ageing is caused by both genetic and environmental factors is now generally accepted, even though it remains difficult to distinguish between ageing sensu stricto and the effects of age-related diseases. Empirical data show that mechanisms of ageing are highly conserved during evolution. Moreover, it has been established that there are specific molecular ‘instructions’ for ageing, which suggests that a better understanding of the molecular biology of ageing will open new possibilities regarding future interventions. The complexity of ageing diminishes the possibility that any general theory will completely explain this metaphenomenon. Likewise, it is highly unlikely that any medication can stop or reverse human senescence. Nevertheless, ageing as a dynamic and malleable metaphenomenon can be modulated by a variety of influences. The concept of the shrinkage of the homeo­dynamic space with age, i.e. homeostenosis, is especially interesting and intriguing as it shows that novel therapeutic approaches and rational strategies can help delay the onset of the ageing-associated pathologies by enhancing the homeodynamic capabilities of the body. The aim of this article is to present current data from evolutionary and molecular gerontology and discuss them within the ambit of this review which is devoted to the dynamic, emergent and plastic nature of human ageing and implications for future inter­ventions.

Downloads

Download data is not yet available.

References

Arking R. 2019. Biology of longevity and aging. Pathways and prospects. 4th ed. New York: Oxford University Press.
View in Google Scholar

Barbosa MC, Grosso RA, Fader CM. 2019. Hallmarks of aging: an autophagic perspective. Front Endocrinol 9:790.
View in Google Scholar

Bergamini E, Cavallini G, Donati A, Gori Z. 2007. The role of autophagy in aging: its essential part in the anti-aging mechanism of caloric restriction. Ann NY Acad Sci 1114:69–78.
View in Google Scholar

Blagosklonny MV. 2008. Aging. ROS or TOR. Cell Cycle 7:3344–54.
View in Google Scholar

Blagosklonny MV. 2010. Calorie restriction: Decelerating mTOR-driven aging from cells to organisms (including humans). Cell Cycle 9:683–8.
View in Google Scholar

Blagosklonny MV. 2012. Answering the ultimate question “What is the proximal cause of aging?”. Aging 4:861–77.
View in Google Scholar

Blagosklonny MV. 2013. Damage-induced aging and perpetual motion. Cell Cycle 12:2709–10.
View in Google Scholar

Blagosklonny MV. 2017. From rapalogs to anti-aging formula. Oncotarget 8:35492–507.
View in Google Scholar

Blagosklonny MV. 2018. Disease or not, aging is easily treatable. Aging 10:3067–78.
View in Google Scholar

Boffetta P, Hainaut P. 2019. Encyclopaedia of cancer. 3rd ed. New York: Elsevier.
View in Google Scholar

Bulterijs S, Hull RS, Björk VC, Roy AG. 2015. It is time to classify biological aging as a disease. Front Genet 6:205.
View in Google Scholar

Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. 2019. From discoveries in ageing research to therapeutics for healthy ageing. Nature 571:183–92.
View in Google Scholar

Carnes BA, Olshansky SJ, Hayflick L. 2013. Can human biology allow most of us to become centenarians? J Gerontol A Biol Sci Med Sci 68:136–42.
View in Google Scholar

Chmielewski P. 2016. The relationship between adult stature and longevity: tall men are unlikely to outlive their short peers – evidence from a study of all adult deaths in Poland in the years 2004–2008. Anthropol Rev 79:439–60.
View in Google Scholar

Chmielewski P. 2017. Rethinking modern theories of ageing and their classification: the proximate mechanisms and the ultimate explanations. Anthropol Rev 80:259–72.
View in Google Scholar

Chmielewski P. 2018. Leukocyte count, systemic inflammation, and health status in older adults: a narrative review. Anthropol Rev 81:81–101.
View in Google Scholar

Chmielewski PP. 2019a. Human ageing as a dynamic, emergent and malleable process: from disease-oriented to health-oriented approaches. Biogerontology, accepted manuscript available at https://doi.org/10.1007/s10522-019-09839-w
View in Google Scholar

Chmielewski PP. 2019b. Human ageing, longevity and evolution: can ageing be programmed? Anthropol Rev 82:417–33.
View in Google Scholar

Chmielewski P, Borysławski K, Strzelec B. 2016a. Contemporary views on human aging and longevity. Anthropol Rev 79:115–42.
View in Google Scholar

Chmielewski PP, Borysławski K, Chmielowiec K, Chmielowiec J, Strzelec B. 2016b. The association between total leukocyte count and longevity: Evidence from longitudinal and cross-sectional data. Ann Anat 204:1–10.
View in Google Scholar

Chmielewski PP, Strzelec B. 2018. Elevated leukocyte count as a harbinger of systemic inflammation, disease progression, and poor prognosis: a review. Folia Morphol 77:171–8.
View in Google Scholar

Cohen AA. 2016. Complex systems dynamics in aging: new evidence, continuing questions. Biogerontology 17:205–20.
View in Google Scholar

da Costa JP, Vitorino R, Silva GM, Vogel C, Duarte AC, Rocha-Santos T. 2016. A synopsis on aging-Theories, mechanisms and future prospects. Ageing Res Rev 29:90–112.
View in Google Scholar

de Magalhães JP. 2012. Programmatic features of aging originating in development: aging mechanisms beyond molecular damage? The FASEB Journal 26(12):4821–6.
View in Google Scholar

Demetrius L. 2005. Of mice and men. When it comes to studying ageing and the means to slow it down, mice are not just small humans. EMBO reports 6:S39–S44.
View in Google Scholar

Demirovic D, Rattan SI. 2013. Establishing cellular stress response profiles as bio-markers of homeodynamics, health and hormesis. Exp Gerontol 48:94–8.
View in Google Scholar

De Santi M, Baldelli G, Diotallevi A, Galluzzi L, Fiorella G, Schiavano GF, Brandi G. 2019. Metformin prevents cell tumorigenesis through autophagy-related cell death. Sci Rep 9:66.
View in Google Scholar

DiLoreto R, Murphy CT. 2015. The cell biology of aging. Mol Biol Cell 26:4524–31.
View in Google Scholar

Dönertaş HM, Fuentealba M, Partridge L, Thornton JM. 2019. Identifying potential ageing-modulating drugs in silico. Trends Endocrinol Metab 30:118–31.
View in Google Scholar

Fang J, Gao L, Ma H, Wu Q, Wu T, Wu J, Wang Q, Cheng F. 2017. Quantitative and systems pharmacology 3. Network-based identification of new targets for natural products enables potential uses in aging-associated disorders. Front Pharmacol 8:747.
View in Google Scholar

Fernández AF, Fraga MF. 2011. The effects of the dietary polyphenol resveratrol on human healthy aging and lifespan. Epigenetics 6:870–4.
View in Google Scholar

Fougère B, Boulanger E, Nourhashémi F. 2017. Chronic inflammation: accelerator of biological aging. J Gerontol A Biol Sci Med Sci 72:1218–25.
View in Google Scholar

Franceschi C, Campisi J. 2014. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69:S4–9.
View in Google Scholar

Gandini S, Puntoni M, Heckman-Stoddard BM, Dunn BK, Ford L, DeCensi A, Szabo E. 2014. Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res 7:867–85.
View in Google Scholar

Gems D. 2015. The aging-disease false dichotomy: understanding senescence as pathology. Front Genet 6:212.
View in Google Scholar

Ginés C, Cuesta S, Kireev R, García C, Rancan L, Paredes SD, Vara E, Tresguerres JAF. 2017. Protective effect of resveratrol against inflammation, oxidative stress and apoptosis in pancreas of aged SAMP8 mice. Exp Gerontol 90:61–70.
View in Google Scholar

Hayflick L. 2004. “Anti-aging” is an oxymoron. J Gerontol A Biol Sci Med Sci 59:B573–8.
View in Google Scholar

Hayflick L. 2007. Entropy explains aging, genetic determinism explains longevity, and undefined terminology explains misunderstanding both. PLoS Genet 3:e220.
View in Google Scholar

Jeyapalan JC, Sedivy JM. 2008. Cellular senescence and organismal aging. Mech Ageing Dev 29:467–74.
View in Google Scholar

Kaczmarek M, Szwed A. 1997. A review of anthropological approaches to ageing. Przegląd Antropologiczny 60:35–46.
View in Google Scholar

Kaczmarek M, Wolański N. 2018. Rozwój biologiczny człowieka od poczęcia do śmierci. Warszawa: Wydawnictwo Naukowe PWN.
View in Google Scholar

Kasznicki J, Sliwinska A, Drzewoski J. 2014. Metformin in cancer prevention and therapy. Ann Transl Med 2:57.
View in Google Scholar

Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE, Rando TA, Richardson A, Schadt EE, Wyss-Coray T, Sierra F. 2014. Geroscience: linking aging to chronic disease. Cell 159:709–13.
View in Google Scholar

Kennedy BK, Lamming DW. 2016. The mechanistic target of rapamycin: the grand conductor of metabolism and aging. Cell Metab 23:990–1003.
View in Google Scholar

Kenyon CJ. 2010. The genetics of ageing. Nature 464:504–12.
View in Google Scholar

Kim J, Guan KL. 2019. mTOR as a central hub of nutrient signalling and cell growth. Nat Cell Biol 21:63–71.
View in Google Scholar

Kirkwood TB, Franceschi C. 1992. Is aging as complex as it would appear? New perspectives in aging research. Ann N Y Acad Sci 663:412–7.
View in Google Scholar

Kirkwood TBL. 2005. Understanding the odd science of aging. Cell 120:437–47.
View in Google Scholar

Le Bourg E. 2006. Dietary restriction would probably not increase longevity in human beings and other species able to leave unsuitable environments. Biogerontology 7:149–52.
View in Google Scholar

Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. 2009. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 32:1620–5.
View in Google Scholar

Lloyd D, Aon Ma, Cortassa S. 2001. Why homeodynamics, not homeostasis? Scientific World Journal 1:133–45.
View in Google Scholar

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. 2013. The hallmarks of aging. Cell 153:1194–217.
View in Google Scholar

Masoro EJ. 2006. Dietary restriction-induced life extension: a broadly based biological phenomenon. Biogerontology 7:153–5.
View in Google Scholar

Mau T, Yung R. 2018. Adipose tissue inflammation in aging. Exp Gerontol 105:27–31.
View in Google Scholar

McHugh D, Gil J. 2018. Senescence and aging: causes, consequences and therapeutic avenues. J Cell Biol 217:65–77.
View in Google Scholar

Mitteldorf J. 2013. How does the body know how old it is? Introducing the epigenetic clock hypothesis. Biochemistry 78:1048–53.
View in Google Scholar

Mitteldorf J. 2016. An epigenetic clock controls aging. Biogerontology 17:257–65.
View in Google Scholar

Mitteldorf J. 2017. Aging is a group-selected adaptation: theory, evidence, and medical implications. New York: Taylor & Francis Group.
View in Google Scholar

Mockett RJ, Cooper TM, Orr WC, Sohal RS. 2006. Effects of caloric restriction are species-specific. Biogerontology 7:157–60.
View in Google Scholar

Morrisette-Thomas V, Cohen AA, Fülöp T, Riesco É, Legault V, Li Q, Milot E, Dusseault-Bélanger F, Ferrucci L. 2014. Inflamm-aging does not simply reflect increases in pro-inflammatory markers. Mech Ageing Dev139:49–57.
View in Google Scholar

Muntané G, Farré X, Rodríguez JA, Pegueroles C, Hughes DA, de Magalhães JP, Gabaldón T, Navarro A. 2018. Biological processes modulating longevity across primates: a phylogenetic genome-phenome analysis. Mol Biol Evol 35:1990–2004.
View in Google Scholar

Nilsson G, Hedberg P, Öhrvik J. 2014. White blood cell count in elderly is clinically useful in predicting long-term survival. J Aging Res 2014:475093.
View in Google Scholar

Ocampo A, Reddy P, Martinez-Redondo P, Platero-Luengo A, Hatanaka F, Hishida T, Li M, Lam D, Kurita M, Beyret E, Araoka T, Vazquez-Ferrer E, Donoso D, Roman JL, Xu J, Rodriguez Esteban C, Nuñez G, Nuñez Delicado E, Campistol JM, Guillen I, Guillen P, Izpisua Belmonte JC. 2016. In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell 167:1719–33.
View in Google Scholar

Ortega E, Bote ME, Besedovsky HO, del Rey A. 2012. Hsp72, inflammation, and aging: causes, consequences, and perspectives. Ann NY Acad Sci 1261:64–71.
View in Google Scholar

Potempa M, Jonczyk P, Szczerba K, Kandefer B, Kajdaniuk D. 2016. Metformin – today’s panacea? Clin Diabet 4:117–22.
View in Google Scholar

Proctor MJ, McMillan DC, Horgan PG, Fletcher CD, Talwar D, Morrison DS. 2015. Systemic inflammation predicts all-cause mortality: a Glasgow inflammation outcome study. PLoS One 10:e0116206.
View in Google Scholar

Rattan SIS. 2008. Hormesis in aging. Ageing Res Rev 7:63–78.
View in Google Scholar

Rattan SIS. 2014. Molecular gerontology: principles and perspectives for interventions. In: R Watson, F De Meester, editors. Omega 3 Fatty Acids in Brian and Neurologic Health. New York: Academic Press, Elsevier. 9–18.
View in Google Scholar

Rattan SIS. 2016. If aging is a disease, then it is your own fault. J Aging Sci 4:2.
View in Google Scholar

Rattan SIS. 2018. Biogerontology: research status, challenges and opportunities. Acta Biomed 89:291–301.
View in Google Scholar

Rattan SIS. 2019. Naive extrapolations, over-hyped claims and empty promises in ageing research and interventions need avoidance. Biogerontology, accepted manuscript available at https://link.springer.com/article/10.1007%2Fs10522-019-09851-0
View in Google Scholar

Redman LM, Heilbronn LK, Martin CK, de Jonge L, Williamson DA, Delany JP, Ravussin E; Pennington CALERIE Team. 2009. Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS One 4:e4377.
View in Google Scholar

Rizzo M, Anderson S, Fritzsch B. 2017. The Wiley handbook on the aging mind and brain. New York: Wiley-Blackwell.
View in Google Scholar

Rodier F, Campisi J. 2011. Four faces of cellular senescence. J Cell Biol 192:547–56.
View in Google Scholar

Schneider PL, Bassett DR Jr, Thompson DL, Pronk NP, Bielak KM. 2006. Effects of a 10,000 steps per day goal in overweight adults. Am J Health Promot 21:85–9.
View in Google Scholar

Shanley DP, Kirkwood TB. 2006. Caloric restriction does not enhance longevity in all species and is unlikely to do so in humans. Biogerontology 7:165–8.
View in Google Scholar

Sikora E, Bielak-Zmijewska A, Mosieniak G, Piwocka K.2010.The promise of slow down ageing may come from curcumin. Curr Pharm 16:884–92.
View in Google Scholar

Stambler I. 2015. Has aging ever been considered healthy? Front Genet 6:202.
View in Google Scholar

Stambler I. 2017. Recognizing degenerative aging as a treatable medical condition: methodology and policy. Aging Dis 8:583–9.
View in Google Scholar

Steinberg CEW. 2012. Stress ecology. Environmental stress as ecological driving force and key player in evolution. New York: Springer.
View in Google Scholar

Terman A, Gustafsson B, Brunk UT. 2007. Autophagy, organelles and ageing. J Pathol 211:134–43.
View in Google Scholar

van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slag-boom PE, Westendorp RGJ. 2005. Reduced insulin/IGF-1 signalling and human longevity. Aging Cell 4:79–85.
View in Google Scholar

Villareal DT, Fontana L, Weiss EP, Racette SB, Steger-May K, Schechtman KB, Klein S, Holloszy JO. 2006. Bone mineral density response tocaloric restriction-induced weightloss or exercise-induced weight-loss: a randomized controlledtrial. Arch Intern Med 166:2502–10.
View in Google Scholar

Wang Z. 2018. Aging and aging-related diseases. Mechanisms and interventions. New York: Springer.
View in Google Scholar

Warner HR, Sierra F, Thompson LV. 2010. Biology of Aging. In: H Fillit, K Rockwood, K Woodhouse, editors. Brocklehurst’s Textbook of Geriatric Medicine and Gerontology. 7th ed. New York: Elsevier.
View in Google Scholar

Weindruch R. 2006. Will calorie restriction work in primates? Biogerontology 7:169–71.
View in Google Scholar

Weiss EP, Racette SB, Villareal DT, Fontana L, Steger-May K, Schechtman KB, Klein S, Ehsani AA, Holloszy JO. Washington University School of Medicine CALERIE Group. 2007. Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss. J Appl Physiol 102:634–40.
View in Google Scholar

Witkowski JM. 2009. Dlaczego się starzejemy? In: E Sikora G Bartosz JM Witkowski, editors. Biogerontologia. Warszawa: Wydawnictwo Naukowe PWN.
View in Google Scholar

Yu BP. 2006. Why calorie restriction would work for human longevity. Biogerontology 7:179–82.
View in Google Scholar

Zając-Gawlak I, Pośpiech D, Kroemeke A, Mossakowska M, Gába A, Pelclová J, Přidalová M, Kłapcińska B. 2016. Physical activity, body composition and general health status of physically active students of the University of the Third Age (U3A). Arch Gerontol Geriatr 64:66–74.
View in Google Scholar

Zambrano E, Martínez-Samayoa PM, Bautista CJ, Deás M, Guillén L, Rodríguez-González GL, Guzmán C, Larrea F, Nathanielsz PW. 2005. Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol 566:225–36.
View in Google Scholar

Zimniak P. 2012. What is the proximal cause of aging? Front Genet 3:189.
View in Google Scholar

Downloads

Published

2020-03-30

How to Cite

Chmielewski, P. P. (2020). The dynamic nature of ageing: novel findings, therapeutic avenues and medical interventions. Anthropological Review, 83(1), 75–92. https://doi.org/10.2478/anre-2020-0001

Issue

Section

Articles