Biology subjects

Shenhar, B.

Publications and source records attributed to Shenhar, B..

3 recordsLinked to original sources

bioRxiv2026

A unified framework links infant vulnerability with aging-related mortality dynamics

A central question in Geroscience is whether early-life mortality, which declines from birth to sexual maturity, and late-life mortality, which grows exponentially in time, can be understood within a shared conceptual framework. We show that stochastic threshold models can explain both phases by incorporating heterogeneity in neonatal vulnerability. Using U.S. National Center for Health Statistics data, we find that infant mortality risk is strongly associated with neonatal clinical markers such as Apgar scores, gestational age, and birth weight, suggesting that initial physiological differences persist across early life. We show that the [~]1/t mortality decline generically arises in stochastic threshold models via depletion of the most vulnerable, across a wide range of model specifications. Incorporating this mechanism into the Saturating-Removal model captures both the early decline and the later Gompertz acceleration, reproducing the full J-shaped mortality curve. Together, our findings link neonatal vulnerability to late-life mortality dynamics within a shared stochastic framework, supporting a life-course perspective on aging and longevity.

systems biology↗

bioRxiv2025

Maximal human lifespan in light of a mechanistic model of aging

Why has maximal human lifespan barely changed in the past two centuries? To understand this we make a mechanistic link between cellular damage, survival curves, and maximum lifespan using a validated stochastic model of damage accumulation and extensive human data. We show that maximal lifespan is set mainly by damage production and clearance rates, as in progeroid syndromes. In contrast, lifestyle factors such as exercise, nutrition, and sleep chiefly reduce stochastic noise and raise the damage level compatible with survival, shifting the median but not the maximum. Similar constraints arise in other mortality models. Our analysis predicts that lifestyle can extend maximal lifespan by at most [~]1 year; substantial gains will require directly perturbing damage production or removal, suggesting specific molecular targets.

systems biology↗

bioRxiv2025

Heritability of human lifespan is about 50% when confounding factors are addressed

The heritability of human lifespan is a fundamental question in biology. Current estimates of heritability are low - twin studies show that about 20-25% of the variation in lifespan is explained by genetics, and some large family pedigree studies suggest it is as low as 7%. However, these studies do not distinguish between deaths driven by intrinsic biological processes and deaths caused by extrinsic factors such as accidents or infections. Here we use mathematical modeling and analyses of twin cohorts raised together and apart to show that extrinsic mortality skews heritability estimates by driving down measured lifespan correlations among twin pairs. We also identify a nonlinear effect of the cutoff age--the minimum age of death included in each study -- on estimates of heritability. Correcting for these factors more than doubles previous estimates, revealing that intrinsic heritability of human lifespan is above 50%. Such high heritability is similar to most other complex human traits. We thus challenge the consensus that genetics has only a minor effect on lifespan and show that genes explain the majority of lifespan variation. Since genes are important, understanding the genetics of longevity can reveal aging mechanisms and inform medicine and public health.

genetics↗