Selected Publications

de Magalhães, JP and Church, GM (2007) "Analyses of human-chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging." Mechanisms of Ageing and Development 128:355-364.

By taking advantage of the GenAge database and comparative genomics, we analyzed the rate of evolution of aging-associated genes and pathways since chimpanzees and humans diverged in order to gather clues about the mechanisms responsible for the evolution of longevity in the human lineage. We show that surprisingly aging-associated genes tend to evolve slower and be more highly conserved than expected by chance. Our results also suggest that different evolutionary forces act on genes associated with aging in different model systems.

de Magalhães, JP et al. (2007) "An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts." Journal of Gerontology: Biological Sciences 62:149-160.

In this study, we employed the AnAge database to demonstrate that metabolic rates, at least in placental mammals, do not correlate with longevity after correcting for the effects of body size and phylogeny. In contrast, we show that growth rate and time to sexual maturity are strongly associated with adult lifespan in mammals.

de Magalhães, JP (2006) "Species Selection in Comparative Studies of Aging and Antiaging Research." In: Conn, PM (ed.), Handbook of Models for Human Aging. Elsevier Academic Press, Burlington, MA, pp. 9-20.

This review focuses on the comparative biology of aging. First, I review common methods for comparing aging between different species using human-chimpanzee comparisons as a case example. Afterwards, I propose a list of species for comparative studies of aging that may allow us to understand why humans age the way they age. Lastly, I suggest species that may feature antiaging strategies.

de Magalhães, JP and Church, GM (2006) "Cells discover fire: Employing reactive oxygen species in development and consequences for aging." Experimental Gerontology 41:1-10.

In this paper, we briefly review the free radical theory of aging and then interpret the role of reactive oxygen species (ROS) in aging under the emerging concept that ROS are crucial signaling molecules used in development and growth.

de Magalhães, JP (2005) "Human disease-associated mitochondrial mutations fixed in nonhuman primates" Journal of Molecular Evolution 61:491-497.

In this work, I identified several mitochondrial genes in which the wild-type allele in non-human primates is a disease-causing allele in humans. These results may be linked to the evolution of human longevity and intelligence, indicating a general pattern of selection on longevity in the course of evolution of the human mitochondrion.

de Magalhães, JP and Sandberg, A (2005) "Cognitive aging as an extension of brain development: A model linking learning, brain plasticity, and neurodegeneration" Mechanisms of Ageing and Development 126:1026-1033.

In this work, we propose a model linking development to brain aging in which childhood events essential for brain development result in neurodegeneration later in life.

de Magalhães, JP and Church, GM (2005) "Genomes optimize reproduction: aging as a consequence of the developmental program" Physiology 20:252-259.

This paper is a revival of the developmental theory of aging, an old but largely ignored theory that argues aging is a result of development. In the context of recent experimental findings, we demonstrate that many, if not most, aspects of aging are "unintended" consequences of development.

de Magalhães, JP et al. (2005) "The influence of genes on the aging process of mice: a statistical assessment of the genetics of aging" Genetics 169:265-274.

In this paper, we tried to establish whether a number of short- and long-lived mouse strains age slower or faster using a statistical approach. Although there are strains for which results were inconclusive, there were a number of novel findings regarding the genes regulating aging in rodents.

de Magalhães, JP et al. (2005) "HAGR: the Human Ageing Genomic Resources" Nucleic Acids Research 33:D537-D543.

The official, academic presentation of HAGR.

de Magalhães, JP (2005) "Open-minded scepticism: inferring the causal mechanisms of human ageing from genetic perturbations" Ageing Research Reviews 4:1-22.

This paper is a review of mechanisms of aging. I follow a systems-biology approach in discussing each theory of aging, resulting in a quite original perspective. Overall, I argue that the free radical theory of aging is unlikely to be correct but that hormonal pathways and DNA metabolism may be related to aging.

de Magalhães, JP (2004) "The Dream of Elixir Vitae." In: Immortality Institute (ed.), The Scientific Conquest of Death: Essays on Infinite Lifespans. Libros En Red, Buenos Aires, pp. 47-62.

First of all, I recommend everyone interest in anti-aging research to buy the book The Scientific Conquest of Death: Essays on Infinite Lifespans. As for my chapter, I put forward a perspective on how we will be able to cure aging, along the lines of my Godseed essay. Rather than merely understanding the human aging process, it is my ultimate aim to cure aging and this chapter offers a number of ideas on how we will be able to progress from understanding to curing aging.

de Magalhães, JP et al. (2004) "Gene expression and regulation in H2O2-induced premature senescence of human foreskin fibroblasts expressing or not telomerase" Experimental Gerontology 39:1379-1389.

In this paper, we employed DNA microarray technology to study gene expression in stress-induced premature senescence in human cells. We also quantified the activity of transcription factors to understand how transcription may be regulated in our cellular model. A number of hypotheses are then put forward to explain the results.

de Magalhães, JP (2004) "From cells to ageing: a review of models and mechanisms of cellular senescence and their impact on human ageing" Experimental Cell Research 300:1-10.

This paper is a review of how cells contribute to aging and how we can study these in vitro. I am critical of many models of aging in vitro and suggest some alternatives for future research.

de Magalhães, JP and Toussaint, O (2004) "Telomeres and telomerase: a modern Fountain of Youth?" Rejuvenation Research 7:126-132.

In this paper we review recent results relating telomeres and telomerase to human aging and debate the potential of telomerase as an anti-aging therapy.

de Magalhães, JP and Toussaint, O (2004) "GenAge: a genomic and proteomic network map of human ageing." FEBS Letters 571(1-3):243-247.

Making use of the GenAge database, we rendered protein-protein interaction maps for pathways previously related to aging. While the proteomic network map of human ageing is still being analyzed, it suggests a relationship between the genetics of development and the genetics of aging.

de Magalhães, JP et al. (2004) "No increase in senescence-associated ß-galactosidase activity in Werner-syndrome fibroblasts after exposure to H2O2" Annals of the New York Academy of Sciences 1019:375-378.

A preliminary but intriguing paper on stress response in Werner fibroblasts. It also features a brief discussion on the role of chromatin structure in progeroid syndromes and aging.

de Magalhães, JP and Toussaint, O (2004) "How bioinformatics can help reverse engineer human aging." Ageing Research Reviews 3(2):125-141.

A review paper on computational biology, genomics, and systems biology and their possible uses for studying aging.

de Magalhães, JP (2004) "Alice's Dilemma." Futures 36(1):85-89.

By far my most poetic academic paper. Given the exponential increase in knowledge, humankind, I argue, will soon face a singularity, a point where all models are abandoned and a new reality rules. Deciding between self-destruction and paradise will be the hardest decision ever by the human race.

de Magalhães, JP (2003) "Is mammalian aging genetically controlled?" Biogerontology 4(2):119-120.

An opinion paper where I argue that precise genetic mechanisms control rate of aging and how finding these mechanisms must be the top priority of gerontology.

de Magalhães, JP (2003) "Winning the war against aging." The Futurist, 37(2):48-50.

Another futuristic vision focusing on aging research and the impact life-extension technology will have on our daily lives and in society.

Adapted version available online

de Magalhães, JP (2002) "The one-man rule." The Futurist, 36(6):41-45.

A vision of the future. The basic premise behind this article is that rapid advances in technology will make weapons of increasing destruction more accessible to everyone. A decrease in privacy and eventually a dictatorship is the most likely future scenario for humankind.

Available online

de Magalhães, JP et al. (2002) "Stress-induced premature senescence in BJ and hTERT-BJ1 human fibroblasts." FEBS Letters 523(1-3):157-162.

An experimental paper showing, for the first time, that telomerase activity does not protect human cells against stress-induced premature senescence.

de Magalhães, JP and Toussaint, O (2002) "The evolution of mammalian aging." Experimental Gerontology 37(6):769-75.

A theoretical paper that presents a new model for the evolution of aging in mammals. Its basic hypothesis is that roughly 135 million years as small, rodent-like animals fostered aging in the primitive mammals whose consequences last until today.