Researchers detail how biological hijackers can change the aging process

The aging process of humans and other organisms can be hijacked by another species, like a virus, for the reproductive or survival advantage of the hijacker, while distorting the age of the host organism, according to a new study.

This novel age-distorter (AD) hypothesis is explored in detail by a research team from the Institute of Systematics, Evolution and Biodiversity (SYEB) at the Sorbonne in France. Their work appears in Ageing Research Reviews, May 31.

The researchers propose that research on aging will benefit from including additional genetic causes of aging that come from another species, typically viruses, parasites, worms or bacteria. They give numerous examples of humans or other organisms where ADs have shortened or sometimes lengthened the life of their hosts, depending on which is more advantageous for the reproduction of the AD.

Current Science Daily asked professor Eric Bapteste, one of the study authors, to elaborate on the AD hypothesis: 

"Our hypothesis is that the aging process of many organisms could be distorted in this way, due to interactions with members of other species that take control over parts of their body, for example by inducing aging in some cells within their hosts," Bapteste said. "Therefore, some organisms--for example, animals, human beings--may appear biologically older than they could be, if they had avoided these unfortunate interactions with manipulative parasites, symbionts, or viruses." 

The article describes how both viruses and non-virus ADs can interfere with host aging at the cellular level. Several common viruses have developed mechanisms "to suppress or modify their host cell apoptotic responses for their own benefit," they write. These include the human papilloma virus, the herpes virus and human adenoviruses.

"A virus needs a host cell to replicate its genetic information," Bapteste said. "More precisely, a virus needs to take control over the cellular machinery of an infected host to reproduce, and a virus uses its own genes to do so. Consequently, the life cycle of a virus and that of its host necessarily go through a stage where a virus and its host share a common body--the infected cell-- but possibly no common interest on the optimal way to use that shared body."

He added, "In the case of age distorting viruses, the virus would take control and specifically distort one aspect of the infected cell biology: How this cell is aging. This would allow the virus to optimize its own reproduction or survival, for instance, when inducing aging of some infected cells weakens the defense mechanisms of its hosts against the viral infection."

The age-distorting process

"Specifically, an age distorter may introduce some additional copies of genes associated with aging in its host, pirated viral copies that were stolen during former infections, and the virus may use these genes, corresponding to the ones normally impacting host aging, to initiate or aggravate the aging process in its host," Bapteste said. "An age distorting virus may also introduce and use genes able to regulate--that is, activate or inactivate--the genes normally associated with its host aging process. Overall, when viruses distort the age of a sufficient number of host cells, it generates an imbalance beyond the cell level. The systemic effects of this, called bystander effects, may further result in the aging of the entire infected organism."

Bapteste gave an example of how this works.

"Currently, HIV likely offers the most documented case of a viral age-distorter of human aging, because HIV uses its own genes to cause cells in the human immune system to age," he said.

He also speculated on how it might work with COVID-19.

"Some studies demonstrate that SARS-CoV-2 takes advantage of senescent host cells, typically in old mice, to enhance its own viral replication," the professor said. "Therefore, if SARS-CoV-2 is demonstrated next to also be able to actively induce the formation of senescent cells, this virus would act as an age-distorter. I do not know if that has been demonstrated but this hypothesis deserves to be tested."

Enhancing traditional views on population genetics and aging

Bapteste discussed how the AD hypothesis enhances traditional explanations of aging, and points to new research avenues.

"Traditional explanations of aging are inspired by population genetics, a science that focuses on how genes change within a given species or even a given population," he said. "Thus, traditionally the genetic causes of aging have been searched for within the genes of organisms from a given species. 

"The age-distorters hypothesis adds to this that organisms are also ‘aged’ by members of other species, because some genetic causes of aging lie outside the species under consideration," he added. "This first expansion of traditional explanations suggests searching for causes as well as for candidate regulatory processes of aging, outside the genomes of current aging model species, for example in microbiomes or in infecting viruses."

A second addition to the traditional explanations of aging concerns the "disposable soma" theory, Bapteste said, in which "animals age as selective pressures acting on their species favor organismal reproduction over organismal maintenance – typically, an animal body is disposed of to the benefit of its reproductive cells."

Who owns the aging body?

In this case, "The age-distorter hypothesis invites us to rethink the rules of ownership of an aging body, it encourages us to develop models of aging that explicitly take into account different, conflicting selective pressures which act on the same body and affect its rate of aging," Bapteste said. "Thus, an animal body may be disposed of, not because it benefits this animal's reproductive success but because disposing of this animal body benefits to the reproduction of a symbiont, a virus or a parasite."

A third enhancement of current aging theories concerns a debated topic of how microbes age, Bapteste said. "In theory, the age distorter concept opens a new avenue of research on microbial aging: the investigation of a possible impact of age distorters on unicellular organisms, because microbes too are infected by viruses. And if those viruses would interfere with the aging of a single cell, it would be enough to interfere with the aging of the entire organism."

AD's larger implications

Looking at the larger picture of human genetics, Bapteste suggested that the age distorter hypothesis could point to new insights into the aging process. 

"By discovering and by studying how other entities use their genes to distort our own aging, we could learn more about the genetic pathways involved in our own aging, about what human genes, preferentially pirated or targeted by age distorters, are critical to affect our aging rate," he said. "We could also learn about how to regulate aspects of our aging process by identifying genes able to achieve this in our age-distorters. In other words, we would then know more about human genetics by investigating, how, in nature, this genetics is manipulated by entities that live in us and exploit us."

This could have a very practical effect, and Bapteste pointed out, "This knowledge might encourage searching for new ways to fight against an aspect of aging, 'manipulated aging,' by targeting our age-distorters with drugs, or by using age-distorters to our own advantage."

Bapteste also addressed the implications of AD for evolutionary biology.

"To address the question 'why do we age,' we will be encouraged to enhance current evolutionary theories of aging by integrating more explicit models of the systemic and ecological causes of aging that capture the impact of interspecific interactions, in particular at the genetic level," he said. "We will be encouraged to also think of aging as a result of a genetic arms race and co-evolution."

Regarding future research, Bapteste is curious about what might be discovered. 

"The extent of age-distortion in nature is currently unknown," he said. "Viruses possibly play a larger role in aging than we currently recognize. It is exciting to imagine that the concepts of age-distorters and of age-distorting genes may prompt a systematic search for genes and entities able to manipulate aging across the species borders, and that such a question may become a more visible aspect of mainstream aging studies."