Analysis of aged and cataract lenses shows the presence of increased amounts of crystallin fragments in the high molecular weight aggregates of water-soluble and water-insoluble fractions. However, the significance of accumulation and interaction of low molecular weight crystallin fragments in aging and cataract development is not clearly understood. In this study, twenty three low molecular weight (< 3.5 kDa) peptides in the urea-soluble fractions of young, aged and aged cataract human lenses were identified by mass spectroscopy. Two peptides, B_1-18 (MDIAIHHPWIRRPFFPFH) and A3/A1_59-74 (SD(N)AYHIERLMSFRPIC), present in aged and cataract lens but not young lens, and a third peptide, S_167-178 (SPAVQSFRRIVE) present in all three lens groups were synthesized to study the effects of interaction of these peptides with intact -, - and -crystallins and alcohol dehydrogenase (ADH), a protein used in aggregation studies. Interaction of B_1-18 and A3/A1_59-74 peptides increased the scattering of light by - and -crystallin and ADH. The ability of -crystallin subunits to function as molecular chaperones was significantly reduced by interaction with B_1-18 and A3/A1_59-74 peptides whereas, S peptide had no effect on chaperone-like activity of -crystallin. The A3/A1_59-74 peptide caused a 5.64-fold increase in B-crystallin oligomeric mass and partial precipitation. Replacing hydrophobic residues in B_1-18 and A3/A1_59-74 peptides abolished their ability to induce crystallin aggregation and light scattering. Our study suggests that interaction of crystallin-derived peptides with intact crystallins could be a key event in age-related protein aggregation in lens and cataractogenesis.