SUMMARY While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here we report the effects of maternal age and maternal caloric restriction (CR) on the lifespan and healthspan of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on CR regimens of chronic CR (CCR) or intermittent fasting (IF) had increased lifespan compared to mothers fed ad libitum (AL). With increasing maternal age, lifespan and fecundity of female offspring of AL fed mothers decreased significantly and lifespan of male offspring was unchanged, while body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean lifespan of AL fed female offspring but not male offspring and increasing the fecundity of AL fed female offspring compared to offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, while maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve healthspan and lifespan.

18Maternal age has a negative effect on offspring lifespan in a range of taxa and is hypothesized 19 to influence the evolution of aging. However, the mechanisms of maternal age effects are 20 unknown, and it remains unclear if maternal age alters offspring response to therapeutic 21 interventions to aging. Here, we evaluate maternal age effects on offspring lifespan, 22 reproduction, and the response to caloric restriction, and investigate maternal investment as a 23 source of maternal age effects using the rotifer, Brachionus manjavacas, an aquatic invertebrate. 24 We found that offspring lifespan and fecundity decline with increasing maternal age. Caloric 25 restriction increases lifespan in all offspring, but the magnitude of lifespan extension is greater in 26 the offspring from older mothers. The trade-off between reproduction and lifespan extension 27 under low food conditions expected by life history theory is observed in young-mother offspring, 28 but not in old-mother offspring. Age-related changes in maternal resource allocation to 29 reproduction do not drive changes in offspring fitness or plasticity under caloric restriction in B. 30 manjavacas. Our results suggest that the declines in reproduction in old-mother offspring negate 31 the evolutionary fitness benefits of lifespan extension under caloric restriction. 32 33 KEYWORDS 34 Maternal effects; aging; caloric restriction; evolutionary fitness; maternal investment 35 36 37 38Maternal effects occur when the environment or physiological state of a mother changes the 39 phenotype of her offspring without a corresponding change in genotype. Offspring phenotype 40 may be modified in response to maternal environmental factors including diet, temperature, or 41 exposure to stressors [1][2][3][4][5][6][7][8][9][10][11] . Such maternal effects may be adaptive as in Daphnia and rotifers, in 42 which offspring hatch with protective spines upon maternal exposure to predators [2][3][4][5][6]12 , or as in 43 plants, in which offspring have higher rates of germination and survival when planted in the 44 same high-light or low-light environment as their parent 7,8 . Alternatively, maternal effects may 45 be detrimental as is the case in the negative health outcomes for children due to excessive 46 maternal smoking or alcohol consumption during pregnancy [13][14][15] . We are beginning to 47 understand that maternal effects may be mediated by a variety of epigenetic mechanisms, 48 including direct transmission of maternal proteins, mRNA, lncRNA, miRNA, and modifications to 49 DNA and histones [16][17][18][19][20] . While maternal effects have long been studied and are well known in 50 the ecological literature, there has been a recent rise in interest in maternal effects in the context 51 of human health and aging 21 . 53Maternal age, or the age of a mother at the time her offspring are born, has been shown to have 54 a negative effect on offspring health in a range of taxa [22][23][24][25][26][27][28][29][30][31][32] . A decrea...

Maternal age has a negative effect on offspring lifespan in a range of taxa and is hypothesized to influence the evolution of aging. However, the mechanisms of maternal age effects are unknown, and it remains unclear if maternal age alters offspring response to therapeutic interventions to aging. Here, we evaluate maternal age effects on offspring lifespan, reproduction, and the response to caloric restriction, and investigate maternal investment as a source of maternal age effects using the rotifer, Brachionus manjavacas , an aquatic invertebrate. We found that offspring lifespan and fecundity decline with increasing maternal age. Caloric restriction increases lifespan in all offspring, but the magnitude of lifespan extension is greater in the offspring from older mothers. The trade-off between reproduction and lifespan extension under low food conditions expected by life history theory is observed in young-mother offspring, but not in old-mother offspring. Age-related changes in maternal resource allocation to reproduction do not drive changes in offspring fitness or plasticity under caloric restriction in B. manjavacas . Our results suggest that the declines in reproduction in old-mother offspring negate the evolutionary fitness benefits of lifespan extension under caloric restriction.