Huson, H. J. | bioRxiv Science

bioRxiv2026

Thermodynamic scaling of canine aging and reversible clock deceleration by a reverse transcriptase inhibitor

Aging was tracked in a cohort of 99 "retired" sled dogs over four years to characterize the latent dynamics of physiological decline. Animals were randomized to receive either placebo or the reverse transcriptase inhibitor lamivudine for [~]30 months. We employed a variational autoregressive model to integrate longitudinal blood parameters and DNA methylation (DNAm) profiles. The model defines Biological Age (BA) as a signature of irreversible damage with Poissonian statistics, a feature conserved across mammalian scales. Lamivudine modulated age-independent latent variables and temporarily decelerated the DNAm clock in females, but these effects were reversible upon treatment discontinuation and did not alter the long-term BA trajectory. Critically, we show that physiological fluctuations are governed by a single systemic factor - an effective or phenotypic temperature representing an emergent (macroscopic) property. We show that while the rate of damage accumulation (the BA slope) is independent of this temperature, actuarial aging parameters (initial mortality and the Gompertz exponent) are strongly temperature dependent. This supports a model where mortality arises from effective activation across a protective free energy barrier that erodes with age. These findings identify phenotypic temperature as an important control variable governing the kinetics of organism-level failure, offering a compelling target for interventions aimed at extending healthspan by "squaring" the survival curve.

systems biology↗

bioRxiv2018

Combining landscape genomics and ecological modelling to investigate local adaptation of indigenous Ugandan cattle to East Coast fever

East Coast fever (ECF) is a fatal sickness affecting cattle populations of eastern, central, and southern Africa. The disease is transmitted by the tick Rhipicephalus appendiculatus, and caused by the protozoan Theileria parva parva, which invades host lymphocytes and promotes their clonal expansion. Importantly, indigenous cattle show tolerance to infection in ECF-endemically stable areas. Here, the putative genetic bases underlying ECF-tolerance were investigated using molecular data and epidemiological information from 823 indigenous cattle from Uganda. Vector distribution and host infection risk were estimated over the study area and subsequently tested as triggers of local adaptation by means of landscape genomics analysis. We identified 41 and seven candidate adaptive loci for tick resistance and infection tolerance, respectively. Among the genes associated with the candidate adaptive loci are PRKG1 and SLA2. PRKG1 was already described as associated with tick resistance in indigenous South African cattle, due to its role into inflammatory response. SLA2 is part of the regulatory pathways involved into lymphocytes proliferation. Additionally, local ancestry analysis suggested the zebuine origin of the genomic region candidate for tick resistance.\n\nAuthor summaryThe tick-borne parasite Theileria parva parva infects cattle populations of eastern, central and southern Africa, by causing a highly fatal pathology called \"East Coast fever\". The disease is especially severe for the exotic breeds imported to Africa, as well as outside the endemic areas of East Africa. In these regions, indigenous cattle populations can survive to infection, and this tolerance might result from unique adaptations evolved to fight the disease. We investigated this hypothesis by using a method named \"landscape genomics\", with which we compared the genetic characteristics of indigenous Ugandan cattle coming from areas at different infection risk, and located genomic sites potentially attributable to tolerance. In particular, the method pinpointed two genes, one (PRKG1) involved into inflammatory response and potentially affecting East Coast fever vector attachment, the other (SLA2) involved into lymphocytes proliferation, a process activated by T. parva parva infection. Our findings can orientate future research on the genetic basis of East Coast fever-tolerance, and derive from a general method that can be applied to investigate adaptation in analogous host-vector-parasite systems. Characterization of the genetic factors underlying East Coast-fever-tolerance represents an essential step towards enhancing sustainability and productivity of local agroecosystems.

evolutionary biology↗