Early Life Interventions: Impact on Aging and Longevity

Abstract

Across mammals, lifespans vary remarkably, spanning over a hundredfold difference. Comparative studies consistently reveal a strong inverse relationship between developmental pace and lifespan, hinting at the potential for early-life interventions (ELIs) to influence aging and lifespan trajectories. Focusing on postnatal interventions in mice, this review explores how ELIs influence development, lifespan, and the underlying mechanisms. Previous ELI studies have employed a diverse array of approaches, including dietary modifications, manipulations of the somatotropic axis, and various chemical treatments. Notably, these interventions have demonstrated significant impacts on aging and lifespan in mice. The underlying mechanisms likely involve pathways related to mitochondrial function, mTOR and AMPK signaling, cellular senescence, and epigenetic alterations. Interestingly, ELI studies may serve as valuable models for investigating the complex regulatory mechanisms of development and aging, particularly regarding the interplay among somatic growth, sexual maturation, and lifespan. In addition, prior research has highlighted the intricacies of experimental design and data interpretation. Factors such as timing, sex-specific effects, administration methods, and animal husbandry practices must be carefully considered to ensure the reliability and reproducibility of results, as well as rigorous interpretation. Addressing these factors is essential for advancing our understanding of how development, aging, and lifespan are regulated, potentially opening avenues for interventions that promote healthy aging.

Figure 1.

Potential impact of the time window on early-life intervention effects on lifespan: The curves represent the 7-day rolling average growth rates (g/day) of female (red) and male (blue) UM-HET3 pups [[62] and unpublished data]. Previous studies on the effects of ELIs are shown for reference (a-g) [23, 25, 30, 52, 53, 59]. Lighter and dark green bars indicate longevity alterations observed in one sex or both sexes. Black dot bars indicate no significant change in lifespan. a. Rapamycin treatment, days 1 to 45, increased the longevity of male UM-HET3 mice. b. CR in the first 3 weeks extended the lifespan of male UM-HET3 mice. c. Metformin treatment at day 3, 5, 7 extended lifespans of 129S males. d. Rapamycin treatment, day 4 to 30, significantly extended the lifespan of male and female CD1 mice. e. GH treatment, day 14 to 56, significantly reduced the lifespan of female and male AD mice. f. GH treatment, day 28 to 105, did not alter the lifespan of Snell dwarf mice. g. Rapamycin treatment, day 30 to 60, did not alter the lifespan of CD1 mice. The VO and PS of UM-HET3 pups, occur between day 21 to 43 and day 24 to 30 [62].